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Although endovascular repair (EVAR) is the first-line treatment for abdominal aortic aneurysm, type 2 endoleak (EL), which is associated with late sac enlargement or rupture, remains a concern. The present study aimed to assess the influence of type 2 EL on long-term outcomes after EVAR.Among 550 patients who underwent EVAR between 2007 and 2013 at 14 Japanese national hospitals, 135 patients had type 2 EL diagnosed on follow-up computed tomography (CT) within 12 months after EVAR (EL2[+] group) and 415 patients did not have EL within 12 months (EL2[-] group). The cumulative incidences of sac enlargement, late intervention, and aneurysm-related death after EVAR were estimated using the cumulative incidence function method, and prognostic factors were investigated using the Fine-Gray hazard model.The median follow-up period was 5 years, and the 5-year cumulative incidence rates of sac enlargement, late intervention, and aneurysm-related death were 30.7% ± 4.4%, 25.3% ± 4.1%, and 2.6% ± 1.4%, respectively, in the EL2(+) group, and 8.7% ± 1.6%, 7.6% ± 1.4%, and 0.3% ± 0.3%, respectively, in the EL2(-) group. The cumulative incidence rates of sac enlargement (P = 0.002), late intervention (P 0.001), and aneurysm-related death (P = 0.015) were significantly different between the 2 groups. As the first-line treatment for sac enlargement with type 2 EL, transcatheter coil embolization was performed in 30 patients. Information about sac behavior on CT after coil embolization was available in 20 of the 30 patients. Among these patients, no patients experienced sac shrinkage, and the aneurysmal sac dilated after coil embolization in 18 patients.Type 2 EL affects the long-term outcomes after EVAR. It is not recommended to observe large aneurysmal sacs conservatively as they tend to dilate in the presence of type 2 EL.

Background Stent thrombosis (ST) is a rare but serious complication after deployment of a drug-eluting stent. The features of ST after implantation of an everolimus-eluting stent (EES) have not been fully elucidated. Methods A comprehensive survey of real-world adverse event reporting with conditions for approval under the Pharmaceuticals and Medical Devices Act identified 490 cases of ST with EES. A total of 370 patients with definite ST after EES implantation [287 with early (E)ST (within 30 days), 54 with late (L)ST (31–365 days), and 29 with very late (VL)ST (over 1 year)] were divided into an EST group and an LST/VLST group to compare the patients and lesions characteristics. Results The frequency of patients with hemodialysis and in-stent restenosis (ISR) lesions were significantly higher in the LST/VLST group than in the EST group (hemodialysis, 22.9% vs 2.7%, p = 0.0001; ISR lesions, 25.9% vs 9.4%, p = 0.0001). Characteristic demographic factors for LST/VLST versus EST identified by multivariable model were hemodialysis and ISR lesions (hemodialysis: odds ratio 7.348, 95% confidence interval 2.458–21.968, p = 0.0001; ISR lesions: odds ratio, 2.490, 95% confidence interval 1.100–5.638, p = 0.027). The in-hospital death rates from ST were not significantly different between the EST group and the LST/VLST group (EST, 15% vs LST/VLST, 21.7%, p = 0.147). Conclusions Patient-related and lesion-related characteristics were significantly different between EST and LST/VLST. Data collection from adverse event reporting could be a helpful strategy for evaluation of this serious but rare complication.

Future development of innovative artificial organs is closely related with cutting edge emerging technology. These technologies include brain machine or computer interface, organs made by three dimensional bioprinting, organs designed from induced-pluripotent stem cell for personalized tissue or organ, and xenotransplantation. To bridge the gap between scientific innovation and regulatory product review, Pharmaceuticals and Medical Devices Agency of Japan (PMDA) started the science board to discuss about the new scientific topics regarding medical products including medical device and regenerative products with external experts since 2012. Topics which PMDA raised for science board included cellular and tissue-based products from iPS cells, artificial intelligence and genome editing technology. In addition, PMDA started the horizon scanning to identify a new cutting edge technology which could potentially lead to innovative health technology or product, which has a strong impact on clinical medicine. Although the effectiveness and safety of the medical products must be reasonably assured before clinical use, PMDA introduced Sakigake review assignment (a review partner of device development) and conditional approval system to balance between pre-market and post-market evaluation.

BACKGROUND The influences of co-prescribed medications for chronic co-morbid conditions in very older adults on clinical dementia onset are uncertain.OBJECTIVE To evaluate the influences of co-prescribed medications on clinical dementia onset, which was indicated by the initiation of a new prescription of anti-dementia medication (NPADM).METHODS This retrospective cohort study consisted of 42024 adults aged ≥77 years residing in a suburban city of Tokyo Metropolitan Area who did not take any anti-dementia medication on April 1, 2012. The primary outcome was NPADM during followed-up period until March 31, 2015 (35 months). Subjects were categorized into four age groups: Group I (77-81 years), Group II (82-86 years), Group III (87-91 years), and Group IV (≥92 years). Covariates were fourteen groups of medications prescribed between April 1, 2012 and June 31, 2012. RESULTS In a follow-up period of 1345457 patient-months (mean=32.0±7.5 months), NPADM occurred in 2365 subjects. NPADM incidence at 12 months was 1.9±0.1% (Group I: 0.9±0.1%, Group II: 2.1±0.1%, Group III: 3.2±0.2% and Group IV: 3.6±0.3%; PP=0.001), antihypertensives (0.80, 0.71-0.85; PP=0.002), antidepressants (1.79, 1.47-2.18; PP=0.002), insulin (1.34, 1.01-1.78; P=0.046) and antineoplastics (1.12, 1.01-1.24; P=0.035)CONCLUSIONS These findings provide a benchmark for the management of dementia in the real-world setting, and contribute to evidence-based healthcare policymaking. (Clinical Trial Registration: UMIN-CTR UMIN000039040)

Background Stent thrombosis (ST) is a serious complication after drug-eluting stents (DES) implantation. To identify the risk factors of mortality following ST, we evaluated adverse event reports used for safety measures after approval.Methods and Results:Between July 2004 and August 2019, 2,887 ST case reports were submitted to the Pharmaceutical and Medical Device Agency. Reports of probable or possible ST (n=604), with insufficient data regarding in-hospital outcome or duration between procedure and ST occurrence (n=37) or duplicate reports (n=191) were excluded. Accordingly, 2,045 reports with definite ST were analyzed. Among the subjects, there were 286 in-hospital deaths (14.0%). Multivariate logistic regression analysis revealed that left main trunk (LMT) (odds ratio [OR]: 4.76, 95% confidence interval [CI]: 3.26-6.96), chronic heart failure (CHF) (OR: 2.88, 95% CI: 1.61-5.14), hemodialysis (OR: 2.69, 95% CI: 1.66-4.36), prior stroke (OR: 2.28, 95% CI: 1.15-4.51), over 70 years old (OR: 1.62, 95% CI: 1.22-2.16), and right coronary artery (OR: 0.41, 95% CI: 0.27-0.63) were independent factors for in-hospital death after DES-ST. Conclusions LMT, CHF, hemodialysis, prior stroke, and older age were independently associated with higher risk of in-hospital death following DES-ST. If target patients have these factors, maximum preventive strategies against ST occurrence, including adequate dual-antiplatelet therapy duration and optimal DES deployment procedures, are required.

For more than 10 years, the Harmonization by Doing (HBD) program, a joint effort by members from academia, industry and regulators from the United States of America (USA) and Japan, has been working to increase timely regulatory approval for cardiovascular devices through the development of practical global clinical trial paradigms. Consistent with this mission and in recognition of the increasing global public health effects of critical limb ischemia (CLI), academic and government experts from the USA and Japan have developed a basic framework of global clinical trials for endovascular devices for CLI. Despite differences in medical and regulatory environments and complex patient populations in both countries, we developed a pathway for the effective design and conduct of global CLI device studies by utilizing common study design elements such as patients' characteristics and study endpoints, and minimizing the effect of important clinical differences. Some of the key recommendations for conducting global CLI device studies are: including patients on dialysis; using a composite primary endpoint for effectiveness that includes 6-month post-procedure therapeutic success and target vessel patency; and using a 30-day primary safety endpoint of perioperative death and major adverse limb events. The proposed approach will be uniquely beneficial in facilitating both the initiation and interpretation of CLI studies and accelerating worldwide CLI device development and innovation.

Objective The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Methods Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative—and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards—the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. Results The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Conclusions Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Objective To analyze the changes in the pharmacotherapy and glycemic control trends in elderly patients with type 2 diabetes mellitus (T2DM) in Japan. Methods We extracted the data of 7,590 patients (5,396 men and 2,194 women; median year of birth: 1945) with T2DM registered in the National Center Diabetes Database for the years 2005 to 2013, and conducted age-stratified (

Bioabsorbable plates and screws (BPS) are now widely used as a well-established internal fixation method for various osteosynthetic surgeries, such as fixation of fractures or osteotomies. One of the BPS’s main advantages is that surgical removal is unnecessary since they are ostensibly fully

Background The introduction of transcatheter aortic valve implantation (TAVI) into Japan was strictly controlled to optimize patient outcomes. The goal of this study was to assess if increasing experience during the introduction of this procedure was associated with outcomes.Methods and Results:The initial 1,752 patients registered in the Japanese national TAVI registry were included in the study. The association between operator procedure number and incidence of the early safety endpoint at 30 days (ESE30) as defined in the Valve Academic Research Consortium-2 consensus document was evaluated. Patients were divided into 4 groups by quartiles of procedure count (Groups I-IV in order of increasing number of procedures). Median patient age was 85 years, and 30.5% were male. The 30-day mortality rate was 1.4% (n=24), and 78 patients (7.9%) experienced 95 ESE30. Among the variables included in the model, ESE30 was associated with non-transfemoral approach (P=0.004), renal dysfunction (Cr >2.0 mg/dL) (P=0.01) and NYHA class III/IV (P=0.04). ESE30 incidence was not significantly different between Groups I-III and Group IV. Spline plots demonstrated that experience of 15-20 cases in total was needed to achieve a consistent low risk of ESE30. Conclusions Increasing experience was associated with better outcomes, but to a lesser degree than in previous reports. Our findings suggested that the risks associated with the learning curve process were appropriately mitigated.

We set up the National Center Diabetes Database with financial support from the National Center for Global Health and Medicine and from the Ministry of Health, Labour and Welfare of Japan. In this report, we describe the structure of this database and present the results of the registry based on the use of this database. Medical records of patients diagnosed as having diabetes and who were visiting either of the two clinics or six hospitals in Japan were registered. In the present report, 8,130 records (5,738 men and 2,392 women) obtained between 2005 and 2010 were analyzed. The demographics of this registry clarified that (1) the population of diabetic patients is becoming older (the average age of diabetic men, 62.1 years old; that of women, 66.7 years old); (2) fewer women patients are diagnosed through health checkups as having diabetes than men patients; (3) ever-smokers are more frequently observed in diabetic patients than in the general population in men aged over 60 and in women aged over 40; (4) 72 % of type 2 diabetic patients become overweight at least once in their life. Men who smoked and men who drank alcohol more than 4 days per week were more frequently observed in type 2 diabetes patients who had never been obese than in those who had been obese at least once. The data obtained from a large number of patients registered at a combination of hospitals and clinics might provide reports accurately reflecting the present status of diabetes in Japan.

The Pharmaceuticals and Medical Devices Agency (PMDA) of Japan advances the fundamental principle that the safety and effectiveness of all medical products must be reasonably assured before they are approved. However, strict premarket evaluation often delays patients from gaining access to some

Background: Sac behavior after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) is considered as a surrogate for the risk of late rupture. The purpose of the study is to assess the sac behavior of AAAs after EVAR. Methods and Results: Late sac enlargement (LSE) (≥5 mm) and late sac shrinkage (LSS) (≥5 mm) were analyzed in 589 consecutive patients who were registered at 14 national centers in Japan. The proportions of patients who had LSE at 1, 3 and 5 years were 2.6% ± 0.7%, 10.0% ± 1.6% and 19.0% ± 2.9%. The proportions of patients who had LSS at 1, 3 and 5 years were 50.1% ± 0.7%, 59.2% ± 2.3% and 61.7% ± 2.7%. Multiple logistic regression analysis identified two variables as a risk factor for LSE; persistent endoleak (Odds ratio 9.56 (4.84–19.49), P

Background Our phase I/IIa clinical trial revealed that intramuscular transplantation of autologous, GCSF-mobilized CD34+ cells was safe, feasible and potentially effective at week 4 and 12 post cellular therapy in 17 patients with chronic critical limb ischemia (CLI) (5 patients with atherosclerotic peripheral arterial disease (PAD) and 12 with Buerger's disease). However, long-term outcome of the cell therapy has yet to be reported. Methods and results Incidence of major clinical events and physiological parameters of limb ischemia were evaluated at week 52, 104, 156 and 208 post CD34+ cell therapy. No patients died by week 104, whereas 3 patients with PAD died by week 156 and 1 patient with Buerger's disease died by week 208 due to cardiac complications. No patients underwent major amputation, whereas 1 patient with Buerger's disease underwent unplanned minor amputation by week 104. CLI-free ratio was 88.2% at week 52 and 104, 92.3% at week 156 and 84.6% at week 208 in all patients. Significant improvement of toe brachial pressure index versus baseline was sustained up to week 208 and that of transcutaneous partial oxygen pressure was kept up to week 156. The Wong-Baker FACES pain rating scale, ulcer size and exercise tolerance significantly improved at week 52, the final evaluation time point, compared with baseline. Subgroup analysis revealed the similar outcome in patients with Buerger's disease. Conclusions Favorable clinical outcomes as well as physiological evidences strongly indicate the long-term benefit of GCSF-mobilized CD34+ cell transplantation for retrieval from CLI, especially in patients with Buerger's disease.

Objective: Early outcomes of open abdominal repair (OS) versus endovascular repair (EVAR) for abdominal aortic aneurysm were retrospectively analyzed, after commercialized devices for EVAR had become available in Japan. Patients and Methods: A total of 781 consecutive patients (OS, n = 522; EVAR, n = 259) were treated at ten medical centers between January 2008 and September 2010. The OS group comprised patients with preoperative shock (SOS, n = 34) and without shock (NOS, n = 488). Results: Patients in the EVAR group were 3 years older than those in the NOS group. There was greater prevalence of hostile abdomen, on dialysis, chronic obstructive pulmonary disease on inhaled drug, and cerebrovascular disease in the EVAR group than in the NOS group. Surgical mortality was 16 cases (2.0% in all patients, EVAR: 0.8%, NOS: 1.4%, SOS: 21%). Hospital stay >30 days was documented in 52 (11%) with NOS, 11 (33%) with SOS, and 8 (3%) with EVAR. Thirty late deaths included 6 aneurysm related death and 14 cardiovascular causes at a mean follow up of 1.0 year. The survival rates freedom from all cause death at one year, were 95 ± 1% in NOS and 94 ± 2% in EVAR respectively. Conclusion: Though significant differences in patient characteristics among three groups were noted, early results were satisfactory.

Objective: Patients and Methods: In order to assess the early outcomes of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) in the Japanese population, a total of 183 patients who had EVAR at eight medical centers of the National Hospital Organization were retrospectively reviewed and registered. The mean number of registered cases in each center was 23 ± 17 (4–50 cases). Patient characteristics were male sex, 84%; mean age, 77 years; age ≥ 80 years, 40%. Results: In-hospital mortality was one case (0.5%). Endoleaks were observed at the end of the procedure in 35 patients (19%: type I: n = 4, II: n = 22, III, n = 3, IV: n = 6). Early morbidity included delayed wound healing or infection (n = 7), deterioration of renal dysfunction (n = 3), stroke (n = 2), postoperative bleeding (n = 2), gastrointestinal complications (n = 2), and peripheral thromboembolism (n = 2). Eleven late deaths included one of unknown cause and six cardiovascular causes at a mean follow up of 1.0 year. Survival rates of freedom from all causes of death and from aneurysm-related death at one year were 95.4% ± 1.7% and 99.5% ± 0.5%, respectively. Interpretation: Although registered patients carry a variety of risks, early outcomes were satisfactory. EVAR is an acceptable alternative treatment modality for treating AAA.

Owing to advances in cardiovascular surgery, patients with cardiovascular disease require improvement of health-related quality of life (QOL) than before. We measured the QOL of patients undergoing cardiovascular surgery using the eight-item Short Form (SF-8) and assessed its usefulness.This was a prospective repeated-measures observational study. The SF-8 questionnaire was completed through interviews with 117 consecutive adult patients undergoing cardiovascular surgery at a single center (Nagara Medical Center, Japan) from April 2006 to March 2008. The SF-8 was evaluated before surgery and at 7 days, 1 month, and 6 months after surgery. The physical and mental scores over time were assessed.Regarding physical status, compared with the normal population, the patients' scores were worse preoperatively and had deteriorated 7 days postoperatively; they gradually got closer to preoperative status a month after the procedure. At 6 months after surgery, all physical scores were higher than before surgery. The mental scores, including a mental component summary score, were inferior to those of the normal population until 1 month postoperatively, and they reached those of the normal population at 6 months.The SF-8 changed with the postoperative time course. It was a useful tool for analyzing the physical and mental QOL of patients who underwent cardiovascular surgery.

A number of preclinical studies have indicated the therapeutic potential of endothelial progenitor cells for vascular regeneration in ischemic diseases. A phase I/IIa clinical trial of transplantation of autologous CD34+ cells, the endothelial and hematopoietic progenitor-enriched fraction, was performed in no-option patients with atherosclerotic peripheral artery disease or Buerger's disease with critical limb ischemia (CLI). CD34+ cells were isolated from the G-CSF-mobilized apheresis product using a magnetic cell sorting system. CD34+ cells (105/kg, n = 6; 5 × 105/kg, n = 8; or 106/kg, n = 3) were injected i.m. into the leg with more severe ischemia. The Efficacy Score, representing changes in the toe brachial pressure index (TBPI), Wong-Baker FACES pain rating scale, and total walking distance 12 weeks after cell transplantation, the primary endpoint, was positive, indicating improvement in limb ischemia in all patients, although no significant dose-response relationship was observed. During the 12-week observation after cell therapy, the Wong-Baker FACES pain rating scale, TBPI, transcutaneous partial oxygen pressure, total or pain-free walking distance, and ulcer size serially improved in all patients. No death or major amputation occurred, and severe adverse events were rare, although mild to moderate events relating to G-CSF and leukapheresis were frequent during the 12-week follow-up. In conclusion, the outcomes of this prospective clinical study indicate the safety and feasibility of CD34+ cell therapy in patients with CLI. Favorable trends in efficacy parameters encourage a randomized and controlled trial in the future. Disclosure of potential conflicts of interest is found at the end of this article.

This case report details our experience with endovascular stent-graft repair for an abdominal aortic aneurysm (AAA) in a patient who was previously treated by left ventricular remodeling for dilated cardiomyopathy. Renal dysfunction with an elevated creatinine level (1.59 mg/dl) was managed by reducing the dose of contrast medium utilizing intravascular ultrasonography. Using a Zenith AAA endovascular device, the aneurysmal sac was successfully excluded and was thrombosed. Endovascular stenting is a good treatment option for abdominal aneurysm repair in patients with poor heart function and renal impairment.

Quantitative myocardial fluorodeoxyglucose positron emission tomography (FDG-PET) for assessing glucose uptake in vivo is reliable in normal rat heart. To assess the applicability of myocardial FDG-PET on multiple occasions in the longitudinal disease process of progressive hypertrophy of rat heart. Six salt-sensitive Dahl rats (Dahl-S) developing progressive hypertrophy with subsequent dilated cardiomyopathy were compared with salt-resistant Dahl rats (controls). FDG-PET was applied twice at early stage (ES: 14–18 weeks) and at late stage (LS: 22–26 weeks) of hypertrophy. Standardized uptake value (SUV) was calculated for comparing between different animal weights and different injection dosages of FDG. For validating the quantitative study, radioactivity of a total of 36 tissue samples was compared with the corresponding PET values. The left ventricular mass in Dahl-S increased by 17% at ES and by 25% at LS. The SUV in Dahl-S was 95% of controls at ES and reduced to 62% at LS (P = 0.023). The heart function started to deteriorate after LS. Linear regression analysis showed a good correlation between the radioactivity of tissue samples and PET values (Y = 1.20X, P < 0.0001, R 2 = 0.979). Small animal PET studies on longitudinal multiple occasions in vivo were feasible and useful for the repeating assessment of glucose uptake. The reduction of glucose uptake in progressive hypertrophy of heart over time may precede its progression to heart failure.

Whether endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) is a relative contraindication in patients with preoperative renal dysfunction (Pre-RD), remains controversial because the contrast medium may induce nephrotoxicity. In this study 1658 patients were treated at ten Japanese medical centers between January 2005 and March 2011 (Open surgery (OS) vs. EVAR: n = 1270 vs. n = 388). They were retrospectively analyzed. Multiple logistic regression analysis (MLRA) with pre- and intra-operative variables was applied to all patients. The endpoints induced onset of new dialysis and postoperative renal dysfunction (Post-RD), were defined as a 50% decrease or more from the preoperative estimated glomerular filtration rate (eGFR) level. Results: Early mortality, Post-RD, incidence of new dialysis in all patients were 1.6% (OS: EVAR = 1.9%:0.8%), 6% (OS: EVAR = 8%:2.3%) and 1.4% (OS: EVAR = 1.5%:1.0%) respectively. MLRA identified operation time, clamp of renal artery as risk factors for Post-RD, and operation time and Pre-eGFR level as risk factors for new dialysis. Conclusion: Although Post-RD was more frequently observed in the OS group, MLRA showed that the choice of OS or EVAR was not a risk factor for Post-RD and new dialysis. It was strongly suggested that using contrast medium during EVAR is not a contraindication to AAA repair in patients with Pre-RD. (This article is a translation of J Jpn Coll Angiol 2014; 54: 13–18.)

Tracheo-innominate artery fistula (TIF) is a surgical emergency with high mortality rates. Reported incidence is 0.1%-1.0% after tracheostomy with peak incidence 3 days to 6 weeks post procedure. TIF is usually fatal once it bleeds. For the successful management of TIF, treatment should be initiated immediately with the special considerations kept in mind. We describe two cases of TIF, and its clinical characteristics are reviewed in accordance with relevant literature.

Background: Although endovascular aneurysm repair (EVAR) Is a first line treatment modality for abdominal aortic aneurysm (AAA), the requirement of late intervention Is still a concern. The purpose of the present study Is to reveal the late intervention After EVAR. Methods: Fourteen national

BACKGROUND The objective of the present study was to assess the hypothesis that the introduction of endovascular aneurysm repair (EVAR) into Japan has expanded the indication of abdominal aortic aneurysm (AAA) repair without increasing surgical mortality. METHODS AND RESULTS From 10 national hospitals, we registered a total of 2,154 consecutive patients (Open surgery [OS]: n=1,577, EVAR: n=577) over 8 years, divided into 4 time periods: Group I (2005-2006: n=522), Group II (2007-2008: n=475), Group III (2009-2010: n=551), Group IV, (2011-2012: n=606). Mean age increased over the 4 time periods (P

Radiation-induced heart disease is an increasingly recognized late sequela of mediastinal radiation therapy for malignant neoplasms. We report four cases of heart transplantation for end-stage heart failure induced by mediastinal radiation therapy. Short-term and intermediate-term results are excellent with all four patients currently surviving a mean of 48 months after transplantation. Neither a second malignancy nor recurrence of the primary malignancy has been observed to date. The early results of heart transplantation for end-stage, radiation-induced heart disease are encouraging.

Background: Successful introduction of trans-catheter aortic valve implantation for selected patients with critical aortic stenosis has raised the question of how to identify appropriate high-risk candidates. Methods and Results: To assess the risk profile of patients undergoing single aortic valve replacement (sAVR), multiple logistic regression analysis was applied for open sAVR (n=7,883) registered in the Japan Cardiovascular Surgery Database to predict surgical mortality. Three subgroup analyses stratified by age

The development of post-transplantation coronary graft disease (CGD) is a major cause of late morbidity and mortality. Recent reports have suggested that CGD is a type of chronic vascular rejection, possibly enhanced by cofactors such as concurrent CMV infection and hyperlipidemia. It remains controversial whether established CGD can be improved by modifications in immunosuppressive therapy. The purpose of this study was to examine whether CsA could reverse or halt the progression of CGD after it was already established. Lewis to Fisher (F-344) heterotopic heart allografts develop CGD resembling human disease. Group 1 (n = 29) had no CsA therapy for chronic rat CMV (RCMV) infection in recipients for 8 weeks before transplant. Group 2 (n = 17) had chronic RCMV infection along with CsA therapy from days 15 to 28 post-transplant. Allografts were killed at 2 and 4 weeks and 90 days post-transplantation. In group 1, leukocyte adhesion to arterial endothelium and intimal hyperplasia were well established at 2 weeks and progressed to stenotic, proliferative arterial lesions at 4 weeks. In group 2, CsA therapy was effective in significantly reversing histologic parameters of vascular rejection such as leukocyte adhesion, intimal proliferation, and periarterial edema at 4 weeks. By 90 days, however, arterial pathology was as severe as in group 1. In conclusion, these results support the hypothesis that CGD is a form of chronic vascular rejection, and once established, can be significantly modified by CsA therapy. These effects are not permanent, and progressive CGD recurs after CsA therapy is discontinued.

The present case report details our experience with the hybrid approach for multiple aneurysms in the aortic arch, thoracoabdominal aorta, and around the aortic bifurcation. Total arch replacement for the arch aneurysm under hypothermic cardiopulmonary bypass with antegrade cerebral perfusion was the first stage of aneurysm repair. Five months later, bifurcated graft replacement with debranching of four abdominal branches was undertaken as the second stage of treatment. Finally, stent-graft repair for chronic dissection of the thoracoabdominal aorta was performed utilizing a Gore-Tex Tag endovascular prosthesis. Over 7 months of treatment, all aneurysms were excluded from the aortic blood flow and pressure without abdominal organ dysfunction except a transiently elevated total bilirubin level. Although the patient had an episode of minor gastrointestinal bleeding after discharge, he is currently leading a normal life without limitations at home 5 months after the stent-graft repair.

Abdominal aortic dissection (AAD) is a rare pathology and potentially causes rupture or other serious complications. This case report details our experience in endovascular aneurysm repair for AAD in a patient who had a history of coronary bypass surgery. Circumferential dissection of terminal aorta showed stenosis of true lumen as well as blood flow present in the pseudolumen. Using Zenith AAA endovascular device, the entry site was closed and the pseudolumen was thrombosed successfully. In the present report, published data on AAD were reviewed and endovascular aneurysm repair as a treatment option has been discussed as well.

The case is reported of a 65-year-old male who required reoperation for early failure of a Freestyle stentless valve aortic root bioprosthesis implanted using the full root technique. The bioprosthesis had been implanted to treat annuloaortic ectasia associated with severe aortic regurgitation (AR). At 18 months postoperatively, a new diastolic murmur developed, though without complaint by the patient. Transthoracic echocardiography demonstrated severe AR with aneurysmal dilatation of the non-coronary porcine sinus of Valsalva. Pseudoaneurysm formation, associated with perforation of the non-coronary sinus of Valsalva of the bioprosthesis, was observed at surgery. On inspection, the pseudoaneurysm had pushed the commissures inward, and had created severe aortic valve regurgitation. No infection or calcification was detected on the Freestyle valve, and the aortic root was successfully reconstructed using a composite graft.

Objective: This study was undertaken to evaluate the long-term results of mitral valve repair for mitral regurgitation.Methods: Between 1991 and 2000, 301 patients with mitral regurgitation underwent mitral valve repair. There were 167 men and 134 women whose mean age was 56±14 years. The patients were comprised of 7 patients in Carpentier's type I, 277 patients in type II, and 17 patients in type III. Chordal replacement with expanded polytetrafluoroethylene sutures had been prospectively applied to repair the anterior mitral leaflet prolapse. Ring annuloplasty was performed in 230 patients (76%). The follow-up was complete and mean follow-up was 67±33 months, for a cumulative follow-up of 1,624 patient-years.Results: There were 5 hospital deaths and 11 late deaths (2 cardiac and 9 noncardiac). All survivors except those with stroke were in the New York Heart Association (NYHA) functional class I or II. At 10 years, the actuarial survival was 90±3%, the freedom from embolism was 86±4%, the freedom from reoperation was 96±2%, and the freedom from valve-related events was 77±4%. At 10 years, the freedom from reoperation in the patients with anterior leaflet prolapse was 90±5%.Conclusions: Mitral valve repair is feasible in most patients with mitral regurgitation and is associated with low mortality and low rates of valve related events. Chordal replacement with expanded polytetrafluoroethylene sutures is effective, safe, and durable at long-term follow-up for patients with anterior leaflet prolapse.

In vivo quantitative assessment of positron emission tomography (PET) with 2-deoxy-2-[fluorine 18]fluorodeoxyglucose (FDG) for rat heart has not been explored because of the theoretical limitation of spatial resolution. Our objective was to assess whether FDG uptake measured by PET is correlated with tissue radioactivity of FDG in rat heart directly measured by an automated gamma counter.Ten Sprague-Dawley rats were used for echocardiographic assessment and FDG-PET. Rats were sacrificed immediately after PET scanning, and the radioactivity of FDG in 4 segmental tissue samples of the middle transverse section was measured. Quantitative PET values in a total of 40 regions of interest, in which partial volume effect was corrected based on the phantom study and wall thickness obtained by echocardiogram, were compared with radioactivity of the corresponding 40 tissue samples. Linear regression analysis revealed that tissue radioactivity of FDG was well correlated with the quantitative PET value (Y = 1.17X; r = 0.985, P.0001).Quantitative FDG-PET for rat heart is a reliable approach for assessing glucose metabolism in vivo after correction is made for partial volume effect. These results can be used for various models of heart disease with repeated studies over the disease process in the same animal.

Background . The outcome of valvular heart operations in patients with previous mediastinal radiation therapy was studied. Methods . This is a single center retrospective study of 60 patients (37 females, 23 males) with a mean age of 62 ± 15 years (28 to 88 years old) operated on from January 1976 to December 1998. Valvular heart operations performed included aortic valve replacements (n = 26), mitral valve procedures (n = 16), tricuspid valve procedures (n = 6), and multiple valve procedures (n = 12). A total of 264 clinical, hemodynamic, electrocardiographic and echocardiographic variables were analyzed. Results . Total follow-up was 199 patient-years with a mean of 3.3 ± 3.1 years and a range of 0 to 12.4 years old. Early mortality was 7 patients (12%). Early mortality in patients with constrictive pericarditis was 40% (4 of 10) compared with 6% (3 of 50) in patients without constrictive pericarditis. By univariate analysis, early mortality was associated with constrictive pericarditis ( p = 0.011), reduced preoperative ejection fraction ( p = 0.015), and longer cardiopulmonary bypass times ( p = 0.037). A total of 14 patients (23%) required permanent pacemaker placement before (n = 7), during (n = 1), or early (n = 6) after valvular heart operations. There were 19 late deaths (malignancies, 7; heart failures, 5; other cardiac, 4; and other noncardiac, 3). Overall survival and freedom from late cardiac death and cardiac reoperation at 5 years for hospital survivors were 66% ± 8%, 82% ± 7%, and 93% ± 4%, respectively. By univariate analysis, late cardiac death was associated with low ejection fraction ( p = 0.002), New York Heart Association (NYHA) functional class IV ( p = 0.004), preoperative congestive heart failure ( p = 0.02), and preoperative atrial fibrillation ( p = 0.038). Eighty-five percent of the discharged patients were in NYHA functional class I or II at follow-up. Conclusions . Early results of valve replacement after mediastinal radiation therapy were good except in the presence of constrictive pericarditis. Long-term outcome was limited by malignancy and heart failure. Early surgical intervention is recommended before the development of risk factors for late death, namely, severe symptoms, left ventricular dysfunction, and atrial fibrillation.

Objectives: Our objectives were to characterize the outcome of coronary artery bypass grafting in patients with previous mediastinal radiation therapy and to identify special features of this condition that relate to surgical management. Patients and methods: We conducted a retrospective review of 47 patients (28 women, 19 men) with a mean age of 63.5 ± 12.8 years (range 31.0-82.9 years) from 1976 through December 1996 undergoing coronary artery bypass graft after mediastinal radiation therapy. Results: The mean interval between mediastinal radiation therapy and coronary artery bypass grafting was 15.1 ± 9.8 years (range 1.1-37.8 years). In the 44 patients with isolated coronary surgery, operative mortality was 3 patients (6.8%). Sternal wound infection occurred in 3 patients (6.8%). Actuarial survival at 1 and 5 years was 87.2% ± 4.9% and 71.6% ± 7.1%, respectively. Total follow-up was 293.7 patient-years (mean 6.2 ± 5.1 years). There were 17 late deaths (malignancy, n=7; heart failure, n=6; stroke, n=1; other noncardiac causes, n=2; and sudden death, n=1). Twelve of 43 discharged patients had the development of valvular disease demonstrated by follow-up echocardiography. Conclusions: The early results of coronary artery bypass grafting for the treatment of ischemic heart disease after mediastinal radiation therapy are good. Late survival, however, is limited by malignancy, either recurrent or new, and the development of heart failure. Inasmuch as 25 other patients after radiation therapy required concomitant valve surgery and 12 of 43 (28%) discharged patients had later development of valvular disease, with 2 requiring reoperation, careful assessment of any valvular lesion is important during the initial coronary artery bypass grafting. Careful follow-up, including regular echocardiographic screening, is recommended in this patient population. (J Thorac Cardiovasc Surg 1999;117:1136-43)

We have devised a simple hypothermic retrograde cerebral circulation technique for protecting the brain during aortic arch surgery. The central venous pressure is simply elevated (15 to 18 mmHg) while the aortic arch is open and the descending aorta occluded, causing oxygen-saturated venous blood from the lower half of the body, which is undergoing deep hypothermic (15°C to 18°C) perfusion, to circulate in the brain in a retrograde fashion, supplying it with oxygen. Twenty-six cases of distal aortic arch aneurysm treated using this method, through a left thoracotomy with femoral vein cannulation, were evaluated. Retrograde cerebral circulation time was 59.6 ± 13.1 minutes (40 to 93 min). Retrograde flow was 43.9 ± 13.0 (25 to 62) mL/min. Significant oxygen and apparent lactate extraction were noted in the brain. Early death resulted in 3 of the first 14 cases (21.4%) from embolism, and in 1 of the other 12 cases (8.3%) from massive bleeding and multiple organ failure. Only one late death occurred. No death was attributed to the method itself. This method, with its simplified operative procedure using a lateral thoracotomy, supplied oxygen to the brain and protected it during interruption of the cerebral circulation. Careful management of the atherosclerotic aorta is needed. (J Card Surg 1994;9:576–583)

La dissection aortique abdominale (AAD) est une pathologie rare et cause potentiellement la rupture ou d’autres complications serieuses. Ce rapport de cas detaille notre experience de la reparation endovasculaire d’anevrysme d’une AAD chez un patient qui avait un antecedent de pontage coronarien. La dissection circulaire de l’aorte terminale montrait une stenose de la vraie lumiere et un flux sanguin dans la fausse lumiere. Avec un dispositif endovasculaire Zenith pour AAA, la porte d’entree etait fermee et la fausse lumiere thrombosee avec succes. Dans le present rapport, les donnees publiees sur les AAD ont ete revues et la reparation endovasculaire comme option therapeutique est discutee.

Background Long term effects of left ventricle (LV) repair surgery (LVR) for ischemic cardiomyopathy are not well understood. Methods and Results Sixty-nine rats developed ischemic cardiomyopathy with large akinetic LV area 4 weeks after the left anterior descending artery was ligated. In a second surgery 4 weeks later, 33 rats underwent LVR by plication of the akinetic LV area (LVR group), and 36 underwent rethoracotomy alone (sham group). No medication was used in either group. All rats survived the second surgery. LV end-diastolic dimension as measured by echocardiography, LV fractional shortening, and the maximal end-systolic pressure-volume relationship (E max ) as calculated from the data by catheter-tipped manometer and echocardiography improved in the LVR group after the second surgery, but LV end-diastolic dimension and E max gradually deteriorated as time passed. LV end-diastolic pressure improved 1 week after LVR but rose significantly 4 weeks after LVR. Brain natriuretic peptide mRNA was lower in the LVR group than in the sham group 1 week after LVR but not 4 weeks postoperatively. Conclusions Initial improvement in LV function and neurohormonal status after LVR did not last for 4 weeks in this rat model when untreated medically. The mechanism of deterioration should be elucidated to improve long-term results of LVR.

Objective: The objective was to determine whether the Cox maze procedure provides adjunctive benefit in patients with atrial fibrillation undergoing mitral valve repair. Methods: We compared the outcome of 39 patients who had the Cox maze procedure plus mitral valve repair between January 1993 and December 1996 (maze group) with that of 58 patients with preoperative atrial fibrillation who had mitral valve repair during the same interval by the same surgeons (control group). Patients in the 2 cohorts were similar for age, gender, preoperative New York Heart Association class III or IV, and duration of preoperative atrial fibrillation. The control group had a higher incidence of previous heart surgery and coronary artery disease. Results: No operative deaths occurred, and 1 patient in each group required pacemaker implantation after the operation. Duration of cardiopulmonary bypass (122 ± 40 minutes vs 58 ± 27 minutes, P < .0001) and hospitalization (12.6 ± 6.4 vs 9.3 ± 3.4 days, P < .0025) were prolonged in patients having the Cox maze procedure. Overall, 2-year survival was similar (92% ± 5% for maze patients and 96% ± 3% for controls). Freedom from atrial fibrillation in the maze group was 74% ± 8% 2 years after the operation compared with 27% ± 7% for the control group (P < .0001). Freedom from stroke or anticoagulant-associated bleeding in the maze group was 100% 2 years after the operation compared with 90% ± 8% in the control group (P = .04). At most recent follow-up, 82% of maze patients were in normal sinus rhythm (53% in control group). Conclusion: The addition of the Cox maze procedure to mitral valve repair is safe and effective for selected patients, and elimination of atrial fibrillation decreased late complications. (J Thorac Cardiovasc Surg 1999;118:628-35)

Background Marketing authorization holders (MAHs) are obligated to report adverse events (AEs) within 15 days (some cases 30 days) to the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan. Methods To analyze the timeliness of AE reporting to the PMDA, 6610 reports for five categories of cardiovascular devices were retrieved. Two durations were calculated: (1) time from the date the AE occurred to that when the MAH captured it (DOC: days); and (2) time from the date of MAH capture to that of MAH report (DCR: days). Number of DOC > 15 days (DOC15) and delayed reports (DCR > 15 or 30 days) were also calculated. Results AEs included 9.2% deaths and 7.5% non-recoveries. DOC15 and delayed reports were 51.0% and 10.9%, respectively. By multivariate analysis, DOC15 was associated with foreign AE, device category, MAH, patient outcome, event category, and AE that had to be reported within 15 or 30 days (AE15/30). Delayed report was associated with device category, MAH, patient outcome, event category, and AE15/30. Comments Although Japanese MAHs complied with the obligation to report AEs, they often failed to share AEs with healthcare providers. Registry may be a potential solution, although the cooperation of healthcare providers to input data is essential., Highlights • Japanese marketing authorization holders (MAHs) complied with the obligation to report adverse events within the legally determined duration. • MAHs often failed to share adverse events with healthcare providers in a timely fashion. • Registry may be a potential solution, although the cooperation of healthcare providers to input data is essential.