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Background: Fatal arrhythmic events (FAEs), such as sudden cardiac death (SCD) and fatal ventricular arrhythmias, are a devastating complication in patients with coronary artery disease (CAD). Therefore, in this study we aimed to assess the incidence of FAEs in more recent Japanese patients with CAD and to examine whether risk stratification of FAEs can still be feasible using the left ventricular ejection fraction (LVEF)., Methods and Results: In the CREDO Kyoto PCI/CABG registry cohorts-2 and -3, there were 25,843 patients with LVEF data who received a first coronary revascularization (LVEF ≤35% group: N=1,671, 35%45%: N=21,503). FAEs were defined as a composite of SCD or hospitalization for serious ventricular arrhythmias. The cumulative 5-year incidence of FAEs was 2.4% and it increased with decreasing LVEF (LVEF ≤35%: 8.84%, 35%45%: 1.67%, log-rank P<0.0001). The adjusted risk of FAEs also increased with decreasing LVEF., Conclusions: LVEF is still a strong independent factor for predicting FAEs in patients with CAD in the PCI era. There was no obvious decrease in the incidence of FAEs between the 2 cohorts. The risk factors for FAEs through the 2 cohorts, other than low LVEF, included age ≥75 years, diabetes, heart failure, hemodialysis, atrial fibrillation, and anemia.

Background: The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear., Method: We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels., Results: Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke., Conclusions: Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

We present a case of a ruptured mycotic coronary aneurysm effectively treated with covered stents and phased surgery. The covered stent, however, became occluded two years later. Because of the low invasiveness, a covered stent treatment may be advantageous over conventional surgery but trade off long-term vascular patency., Learning Objective: To recognize the presence of a ruptured infectious coronary aneurysm after a primary coronary stenting for ST-elevation myocardial infarction.To discuss the treatment strategies for a ruptured infectious coronary aneurysm with a covered stent., Competing Interests: Authors declare no conflict of interests., (© 2023 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Aims: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease., Methods and Results: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001)., Conclusions: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD., Competing Interests: The authors have declared that no competing interests exist.

Objective: We assessed the clinical effectiveness of coronary artery bypass grafting (CABG) in comparison with that of percutaneous coronary intervention (PCI) in octogenarians with triple-vessel disease (TVD) or left main coronary artery (LMCA) disease., Methods: From the CREDO-Kyoto registry cohort-2, 527 patients, who were ≥ 80 years of age and underwent the first coronary revascularization for TVD or LMCA disease, were divided into the CABG group (N = 151) and the PCI group (N = 376)., Results: The median and interquartile range of patient's age was 82 (81-84) in the CABG group and 83 (81-85) in the PCI group (P = 0.10). Patients >  = 85 years of age accounted for 19% and 31% in the CABG and PCI groups, respectively (P = 0.01). The cumulative 5-year incidence of all-cause death was similar between CABG and PCI groups (35.8% vs. 42.9%, log-rank P = 0.18), while CABG showed a lower rate of the composite of cardiac death/MI than PCI (21.7% vs. 33.9%, log-rank P = 0.005). After adjusting for confounders, the lower risk of CABG relative to PCI was significant for all-cause death (HR 0.61, 95% CI 0.43-0.86, P = 0.005), any coronary revascularization (HR 0.25, 95% CI 0.14-0.43, P < 0.001) and the composite of cardiac death/MI (HR 0.52, 95% CI 0.32-0.85, P = 0.009)., Conclusions: CABG compared with PCI was associated with a lower adjusted risk for all-cause death, any coronary revascularization, and a composite of cardiac death/MI in very elderly patients with TVD or LMCA disease. CABG seemed an acceptable option for selected octogenarians with severe coronary artery disease., (© 2021. The Japanese Association for Thoracic Surgery.)

Background: Diabetes is a well-known risk factor for adverse outcomes after coronary revascularization., Objectives: This study sought to determine high-risk subgroups in whom the excess risks of diabetes relative to nondiabetes are particularly prominent and thus may benefit from more aggressive interventions., Methods: The study population consisted of 39,427 patients (diabetes: n = 15,561; nondiabetes: n = 23,866) who underwent first percutaneous coronary intervention (n = 33,144) or coronary artery bypass graft (n = 6,283) in the pooled CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Graft) registry. The primary outcome measure was major adverse cardiovascular and cerebral endpoints (MACCE), which was defined as a composite of all-cause death, myocardial infarction, and stroke., Results: With median follow-up of 5.6 years, diabetes was associated with significantly higher adjusted risks for MACCE. The excess adjusted risks of diabetes relative to nondiabetes for MACCE increased with younger age (≤64 years: adjusted HR: 1.30; 95% CI: 1.19-1.41; P  < 0.001; 64-73 years: adjusted HR: 1.24; 95% CI: 1.16-1.33; P  < 0.001; >73 years: adjusted HR: 1.17; 95% CI: 1.10-1.23; P  < 0.001; P interaction  < 0.001), mainly driven by greater excess adjusted mortality risk of diabetes relative to nondiabetes in younger tertile. No significant interaction was observed between adjusted risk of diabetes relative to nondiabetes for MACCE and other subgroups such as sex, mode of revascularization, and clinical presentation of acute myocardial infarction., Conclusions: The excess risk of diabetes relative to nondiabetes for MACCE was profound in the younger population. This observation suggests more aggressive interventions for secondary prevention in patients with diabetes might be particularly relevant in younger patients., Competing Interests: This study was supported by an educational grant from the Research Institute for Production Development (Kyoto, Japan). Dr Yamaji has received a research grant from Abbott Vascular. Dr Shiomi has received honoraria from Abbott Vascular and Boston Scientific. Dr Morimoto has received lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; and has served on the Advisory Board of Sanofi. Dr Ehara has received honoraria from Abbott Vascular, Bayer, Boston Scientific, Medtronic, and Terumo. Dr Furukawa has received honoraria from Bayer, Kowa, and Sanofi. Dr Nakagawa has received research grants from Abbott Vascular and Boston Scientific; and honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr Kimura has received a research grant from Abbott Vascular; and honoraria from Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi. All the other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Acquired pulmonary vein (PV) stenosis (PVS) is a complication following cardiac catheter intervention. However, very few cases of PVS after surgical ablation have been reported. We herein report a case of stenosis and occlusion at the left atrium to each pulmonary vein after surgical ablation. A 73-year-old woman who had received aortic valve replacement and pulmonary vein isolation 10 months earlier was diagnosed with congestive heart failure accompanied by pulmonary hypertension. Contrast-enhanced computed tomography revealed stenosis and complete occlusion of the left atrium to all four pulmonary veins. Surgical repair was performed via pericardial patch reconstruction of the left atrium to each PV. Treating multiple PV lesions with involvement of the left atrium wall requires tailored methods. However, there have been few reports concerning such methods of reconstruction. We herein report a method of reconstructing the left atrium and pulmonary veins at the same time., (© 2021. The Japanese Association for Thoracic Surgery.)

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, p trend < 0.001). There was increased use of PCI over CABG (73.5%, 81.9%, and 85.2%, p trend < 0.001) and increased prevalence of evidence-based medications use over time. The cumulative 3-year incidence of all-cause death was similar across the 3 cohorts (9.0%, 9.0%, and 9.3%, p = 0.74), while cardiovascular death decreased over time (5.7%, 5.1%, and 4.8%, p = 0.03). The adjusted risk for all-cause death and for cardiovascular death progressively decreased from Cohort-1 to Cohort-2 (HR:0.89, 95%CI:0.80 to 0.99, p = 0.03, and HR:0.80, 95%CI:0.70 to 0.92, p = 0.002, respectively), and from Cohort-2 to Cohort-3 (HR:0.86, 95%CI:0.78 to 0.95, p = 0.004, and HR:0.77, 95%CI:0.67-0.89, p < 0.001, respectively). The risks for stroke and repeated coronary revascularization also improved over time. In conclusions, we found a progressive and substantial reduction of adjusted risk for all-cause death, cardiovascular death, stroke, and repeated coronary revascularization over the past two decades in Japan., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long-term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). Methods and Results Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, we identified the current study population of 3380 patients with three-vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow-up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P =0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28-2.42; P <0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80-1.34; P =0.77). Conclusions There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure.

Chronic kidney disease (CKD) might be an important determinant in choosing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). However, there is a scarcity of studies evaluating the effect of CKD on long-term outcomes after PCI relative to CABG in the population including severe CKD. Among 30257 consecutive patients patients who underwent first coronary revascularization with PCI or isolated CABG in the CREDO-Kyoto PCI/CABG registry Cohort-2 (n = 15330) and Cohort-3 (n = 14,927), we identified the current study population of 12,878 patients with multivessel or left main disease, and compared long-term clinical outcomes between PCI and CABG stratified by the subgroups based on the stages of CKD (no CKD: eGFR >=60 ml/min/1.73m 2 , moderate CKD: 60> eGFR >=30 ml/min/1.73m 2 , and severe CKD: eGFR <30 ml/min/1.73m 2 or dialysis). There were 6,999 patients without CKD (PCI: n = 5,268, and CABG: n = 1,731), 4,427 patients with moderate CKD (PCI: n = 3,226, and CABG: n = 1,201), and 1,452 patients with severe CKD (PCI: n = 989, and CABG: n = 463). During median 5.6 years of follow-up, the excess mortality risk of PCI relative to CABG was significant regardless of the stages of CKD without interaction (no CKD: HR, 1.36; 95%CI, 1.12 to 1.65; p = 0.002, moderate CKD: HR, 1.40; 95%CI, 1.17 to 1.67; p <0.001, and severe CKD: HR, 1.33; 95%CI, 1.09 to 1.62; p = 0.004, Interaction p = 0.83). There were no significant interactions between CKD and the effect of PCI relative to CABG for all the outcome measures evaluated. In conclusion, PCI compared with CABG was associated with significantly higher risk for all-cause death regardless of the stages of CKD without any significant interaction., Competing Interests: Disclosures Dr. Morimoto reports honoraria from Bayer and Kowa, and expert witness from Boston Scientific and Sanofi. Dr. Shiomi reports honoraria from Abbott Vascular, and Boston Scientific. Dr. Furukawa reports honoraria from Bayer, Kowa, and Sanofi. Dr. Nakagawa reports research grant from Abbott Vascular and Boston Scientific, and honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr. Kimura reports honoraria from Abbott Vascular, Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Long-term safety of percutaneous coronary intervention (PCI) as compared with coronary artery bypass grafting (CABG) is still controversial in patients with unprotected left main coronary artery disease (ULMCAD), and there is a scarcity of real-world data on the comparative long-term clinical outcomes between PCI and CABG for ULMCAD in new-generation drug-eluting stents era. The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013, and we identified 855 patients with ULMCAD (PCI: N = 383 [45%], and CABG: N = 472 [55%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.5 (interquartile range: 3.9 to 6.6) years. The cumulative 5-year incidence of all-cause death was not significantly different between the PCI and CABG groups (21.9% vs 17.6%, Log-rank p = 0.13). After adjusting confounders, the excess risk of PCI relative to CABG remained insignificant for all-cause death (HR, 1.00; 95% CI, 0.68 to 1.47; p = 0.99). There were significant excess risks of PCI relative to CABG for myocardial infarction and any coronary revascularization (HR, 2.07; 95% CI, 1.30 to 3.37; p = 0.002, and HR, 2.96; 95% CI, 1.96 to 4.46; p < 0.001), whereas there was no significant excess risk of PCI relative to CABG for stroke (HR, 0.85; 95% CI, 0.50 to 1.41; p = 0.52). In conclusion, there was no excess long-term mortality risk of PCI relative to CABG, while the excess risks of PCI relative to CABG were significant for myocardial infarction and any coronary revascularization in the present study population reflecting real-world clinical practice in Japan., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To examine the efficacy and safety of combination treatment with testosterone replacement therapy plus alternate-day tadalafil (10 mg) in patients with late-onset hypogonadism., Methods: In this open-label, randomized, crossover study, 29 patients with late-onset hypogonadism were randomly assigned to receive testosterone replacement therapy for 12 weeks followed by combination treatment for 12 weeks (Group 1) or combination treatment for 12 weeks followed by testosterone replacement therapy (Group 2). Symptom questionnaires were administered and blood tests were performed prior to and following each treatment to assess safety and efficacy. At the end of the study, participants were asked about their treatment preferences., Results: An adverse effect, a rheum symptom, occurred in only one participant, and 26 participants completed the study without any toxicity. Scores on the Aging Male Symptoms scale and the modified short version of the International Index of Erectile Function, and Overactive Bladder Symptom scores were significantly improved in the combination treatment phase of Group 2, whereas no significant difference between the phases were observed in Group 1. In total, 12 out of the 14 participants in Group 1 and 11 out of the 12 participants in Group 2 preferred combination treatment, which reached statistical significance (P = 0.008 and 0.004 for Groups 1 and 2, respectively)., Conclusions: Testosterone replacement therapy with add-on alternate-day tadalafil is a safe and satisfactory treatment for patients with late-onset hypogonadism., (© 2020 The Japanese Urological Association.)

Glomeruli and renal tubule injury in chronic kidney disease (CKD) is reported to involve induction of macrophage activation through the CCL2/CCR2 axis. The effects of inhibitors of the CCL2/CCR2 axis, such as anti-CCL2 antibody and CCR2 antagonist, on kidney function in animal models or humans with kidney dysfunction have been demonstrated. The N-terminal glutamine on immature CCL2 is replaced with pyroglutamate (pE) by glutaminyl cyclase (QC) and isoQC. pE-CCL2 is stable and resistant to peptidases. We hypothesized that inhibiting QC/isoQC activity would lead to the degradation of CCL2, thereby ameliorating CKD and reducing kidney inflammation. To test this hypothesis, we investigated the renoprotective properties of the QC/isoQC inhibitor PQ529 in anti-glomerular basement membrane (GBM) antibody-induced glomerulonephritis Wistar Kyoto (WKY) rats. Three-week repeated administration of PQ529 (30 and 100 mg/kg, twice daily) significantly reduced the serum and urine CCL2 and urinary protein excretion in a dose-dependent manner. Correlations between the urinary protein level and serum or urinary CCL2 levels were confirmed in tested animals. Repeated administration of PQ529 significantly reduced the expression of CD68, a macrophage marker, in the kidney cortex and mononuclear infiltration into the tubulointerstitium. In addition, decreased levels of urinary KIM-1, β2 microglobulin, and clusterin were detected, suggesting the inhibition of inflammation in both the proximal and distal tubules. These results suggest that PQ529 suppresses the progression of inflammation-induced renal dysfunction by inhibiting the CCL2/CCR2 axis. Inhibition of QC/isoQC may thus be a viable alternative therapeutic approach for treating glomerulonephritis and CKD patients.

Introduction: The best method for administering testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH) remains controversial. This study aimed to compare the efficacy and safety of a combined treatment (CT) involving intramuscular testosterone injection and testosterone ointment application [Glowmin ® (GL)] with intramuscular injection monotherapy (IMIM)., Materials and Methods: Patients were randomly assigned as follows: Group 1 received IMIM for 12 weeks and CT for 12 weeks and Group 2 received CT for 12 weeks and IMIM for 12 weeks. Patients were then asked about their treatment preferences: (A) IMIM, (B) a combination of IMIM and ointment, or (C) either A or B., Results: Patients ( n  = 43) completed the study without any adverse effects. No significant differences between each treatment period were found. In Group 1, most patients chose B ( n  = 13) while in Group 2, most chose A ( n  = 10). In each group, patients preferred the second treatment phase; however, statistical significance was not reached between A and B (Group 1, p  = 0.11 and Group 2, p  = 0.47, respectively)., Conclusion: TRT by CT is compatible with TRT by IMIM. Patients who cannot continue TRT because of polycythemia from IMIM may be suited to CT.

We report a case of pulmonary artery aneurysm and pulmonary stenosis with a quadricuspid pulmonary valve in a 64-year-old woman. While pulmonary artery disease had been found as a child, she needed no treatment because of the absence of symptoms and her normal physical development. She began experiencing dyspnoea on exertion 3 years ago. Echocardiography showed pulmonary artery aneurysm and severe pulmonary stenosis with a quadricuspid valve. Computed tomography showed a pulmonary artery aneurysm extending from its main trunk to the bilateral branches. The pulmonary valve was replaced, and the pulmonary trunk and its bilateral branch were reconstructed. The patient's postoperative course was uneventful., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Although surgical ventricular restoration for ischemic cardiomyopathy is expected as an alternative or bridge to heart transplantation, post-operative remodeling of left ventricle (LV) needs to be addressed. This study aimed to examine the effect of basic fibroblast growth factor (bFGF), which induces angiogenesis and tissue regeneration in ischemic myocardium, to prevent remodeling after surgical ventricular restoration (SVR) using a rat ischemic cardiomyopathy model., Methods: Four weeks after coronary artery ligation, rats were divided into two groups: rats treated with SVR alone (SVR; n = 21), and rats treated with SVR and local sustained release of bFGF using gelatin hydrogel sheet (SVR + bFGF; n = 22). Cardiac function was assessed by serial echocardiography and cardiac catheterization. Cardiac tissue sections were histologically examined for vascular density and fibrosis., Results: Higher systolic function and lower LV end-diastolic pressure (LVEDP) were observed in rats treated with SVR + bFGF (SVR vs SVR + bFGF; Ees: 0.22 ± 0.11 vs 0.33 ± 0.22 mmHg/μL, p = 0.0328; LVEDP: 12.7 ± 7.0 vs 8.5 ± 4.3 mmHg, p = 0.0230). LV area tended to be lower in rats treated with SVR + bFGF compared to rats treated with SVR alone (left-ventricular end-diastolic area: 0.66 ± 0.07 vs 0.62 ± 0.07 cm 2 , p = 0.071). Vascular density tended to be higher in rats treated with SVR + bFGF than those without bFGF (23.3 ± 8.1 vs 28.8 ± 9.5/mm 2 , p = 0.0509)., Conclusions: BFGF induced angiogenesis and attenuated remodeling after SVR which secured the efficacy of SVR in a rat ischemic cardiomyopathy model.

Hypertrophic obstructive cardiomyopathy in Libman-Sacks endocarditis is quite rare and the correct etiological relationship between them is unknown. Some changes may cause a secondary disorganization of the ordinary muscle structure, making a disarray pattern with irregular interwoven myocyte fibers. This case report describes one of the first cases of ventricular septal myectomy and mitral valve replacement for hypertrophic obstructive cardiomyopathy and mitral valve regurgitation associated with Libman-Sacks endocarditis.

Aims: Tricuspid regurgitation (TR) has been reported to be associated with worse survival in various heart diseases, but there are few data in aortic stenosis (AS)., Methods and Results: In the Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis (CURRENT AS) Registry enrolling 3815 consecutive patients with severe AS, there were 628 patients with moderate or severe TR (TR group) and 3187 patients with no or mild TR (no TR group). The study patients were subdivided into the initial aortic valve replacement (AVR) stratum (n = 1197) and the conservative stratum (n = 2618) according to treatment strategy. The primary outcome measure was a composite of aortic valve-related death or hospitalization due to heart failure. The 5-year freedom rate from the primary outcome measure was significantly lower in the TR group than in the no TR group (49.1% vs. 67.3%, P < 0.001). Even after adjusting for confounders, the excess risk of TR relative to no TR for the primary outcome measure remained significant [hazard ratio (HR): 1.25, 95% confidence interval (CI): 1.06-1.48; P = 0.008]. The trend for the excess adjusted risk in the TR group was consistent in the initial AVR and the conservative strata (HR 1.55, 95% CI: 0.97-2.48; P = 0.07; HR 1.22, 95% CI: 1.02-1.46; P = 0.03, respectively). In the initial AVR stratum, the 5-year freedom rate from the primary outcome measure was not different between the two groups with (n = 56) or without (n = 91) concomitant tricuspid annuloplasty (61.5% vs. 72.1%, P = 0.48)., Conclusion: The presence of clinically significant TR concomitant with severe AS is associated with a poor long-term outcome, regardless of the initial treatment strategy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: There is no large-scale study comparing postoperative mortality after aortic valve replacement (AVR) for asymptomatic severe aortic stenosis (AS) between initial treatment with AVR vs. eventual AVR after conservative management., Methods and results: We analyzed data from a multicenter registry enrolling 3,815 consecutive patients with severe AS. Of 1,808 asymptomatic patients, 286 patients initially underwent AVR (initial AVR group), and 377 patients were initially managed conservatively and eventually underwent AVR (AVR after watchful waiting group). Mortality after AVR was compared between the 2 groups. Subgroup analysis according to peak aortic jet velocity (Vmax) at diagnosis was also conducted. There was no significant difference between the 2 groups in 5-year overall survival (OS; 86.0% vs. 84.1%, P=0.34) or cardiovascular death-free survival (DFS; 91.3% vs. 91.1%, P=0.61), but on subgroup analysis of patients with Vmax ≥4.5 m/s at diagnosis, the initial AVR group was superior to the AVR after watchful waiting group in both 5-year OS (88.4% vs. 70.6%, P=0.003) and cardiovascular DFS (91.9% vs. 81.7%, P=0.023)., Conclusions: Asymptomatic severe AS patients who underwent AVR after watchful waiting had a postoperative survival rate similar to those who initially underwent AVR. In a subgroup of patients with Vmax ≥4.5 m/s at diagnosis, however, the AVR after watchful waiting group had worse postoperative survival rate than the initial AVR group.

Objectives: The aim of this study was to identify pathological changes of aortic dissection based on histopathological evaluation of aortic wall weakness by comparing patients with and without congenital abnormalities., Methods: We reviewed records of patients who underwent repair for dissection-related aortic disease between 2008 and 2015. Fifty patients (20 men and 30 women; mean age 66.9 ± 14.0 years) who underwent surgery with subsequent histopathological examination of the aortic wall were divided into 2 groups. Group 1 had congenital abnormalities, including Marfan syndrome and bicuspid aortic valve (n = 5), and Group 2 had no congenital abnormalities (n = 45). We compared the histopathological characteristics of the aortic wall in these patients., Results: There were significant differences in age and body surface area between the 2 groups. Although 80% of Group 1 patients developed dissection at the middle of the media, all Group 2 patients developed dissection at the outer one-third of the media, which is along the pathway of the vasa vasorum of the aortic wall. Both groups showed the same extent of degeneration of the vasa vasorum. Group 1 showed a severe score of mucoid extracellular matrix accumulation in the aortic media., Conclusions: Although it may be multifactorial, congenital maldevelopment of the media tends to result in dissection of the centre of the media, and acquired aortic wall weakness is concentrated in the outer third of the media. Degeneration of the vasa vasorum may be an important emerging substrate for developing aortic dissection.

We report a case of chronic dissecting thoracoabdominal aneurysm with intraoperative retrograde aortic dissection and rupture at proximal descending aorta, which was successfully treated by echoguided stent-graft insertion. An 82-year old male underwent thoracoabdominal aortic replacement for dilatation of infra-diaphragmatic aorta. Under F-F bypass, his thoracoabdominal aorta was replaced by a Dacron graft with 4-branches. After he weaned from F-F bypass, we found massive bleeding from proximal descending aorta. Trans-esophageal echocardiography (TEE) showed aortic dissection from the clamp site to the distal anastomotic site of the former total arch replacement. We temporary got hemostasis by suture and surgical glue, and anastomosed a 10 mm-graft to the thoracoabdominal main graft as conduit, then inserted and deployed 2 pieces of stent-graft. Direct echo and TEE contributed to the accurate positioning of them. Bleeding was completely controlled. He well recovered without paraplegia. Post-operative computed tomography (CT) showed good positioning and dilatation of the stentgraft and the perfect reverse remodeling of thoracic aorta.

Takayasu arteritis (TA) is a rare idiopathic large-vessel vasculitis involving the aorta and its major branches. Coronary artery disease and its surgical management in patients with TA is also a rare clinical entity. We report the case of a 73-year-old woman with TA and 3-vessel coronary artery disease in whom we performed off-pump coronary artery bypass graft concomitant with supra-aortic vessel revascularization., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Primary intimal sarcoma of the heart is an extremely rare tumor that is known to have a very poor prognosis. We present a case of a 65-year-old man who suffered from deteriorating congestive heart failure due to a severe mitral stenosis caused by a large mobile left atrial tumor. The patient underwent an emergency operation of the tumor in the left atrium. The tumor was attached to the inferior wall of the left atrium. After the resection of the tumor, a second tumor on the interatrial septum, which had not been detected in the preoperative investigation, was discovered and resected. The patient developed acute respiratory failure soon after the operation and succumbed to his illness. The appearance of the main tumor was cauliflower-like, which strongly suggested the possibility of malignancy. Immunohistochemistry revealed that the neoplastic cells were positive for vimentin, desmin, p16, and especially murine double minute 2 (MDM-2). The first tumor was CD34 positive and cdk4 negative, but the second tumor was more anaplastic and CD34 negative and cdk4 positive, which suggests a different origin of the two tumors. The two tumors were diagnosed as intimal sarcomas by MDM-2, which is currently considered a conclusive marker. This is an exceptionally rare case of two simultaneous and possibly independent primary intimal sarcomas in the left atrium., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Giant coronary artery aneurysm is a rare clinical entity and its involvement in the interatrial space is extremely rare. We here report the rare surgical case of a 67-year old man with giant right coronary artery aneurysm located in the atrial septum with fistula formation to the right atrium, complicated with congestive heart failure, rapid atrial fibrillation and left atrial appendage thrombus. The patient eventually recovered fully without sequelae., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Fabry's disease is a lysosomal storage disease characterized by intracellular accumulation of ceramide trihexoside resulting from alpha-galactosidase A deficiency. While the heart is often involved, coronary artery disease and its management in Fabry's disease patients are extremely rare clinical entities. We report a case of a 72-year-old man with left main disease in Fabry's disease with special consideration of the arterial wall pathology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We report 2 cases of severe perioperative coronary artery spasm in thoracic aortic surgery. Case 1 was a 72-year-old male with a distal arch aneurysm of 74 mm while case 2 was a 74-year-old male with acute type A aortic dissection. We performed thoracic aortic repair (total arch replacement and ascending aorta replacement) under moderately hypothermic circulatory arrest (25 °C) and selective cerebral perfusion in both cases. ST elevation, abnormal left ventricular wall motion, and hypotension were noted intraoperatively. Because we were not able to wean the patients from the cardiopulmonary bypass, intraaortic balloon pump was initiated in case 1 and a coronary artery bypass graft was added in case 2. In addition to using vasodilators such as diltiazem, case 1 recovered without further intervention, but case 2 developed cardiopulmonary arrest and needed resuscitation on postoperative day 5 because of recurrence of coronary spasm. Perioperative coronary artery spasm is rare especially in aortic surgery, and may become lethal. Early recognition and special hemodynamic support is required.

Purpose: The short-term outcome of physiologic repair for congenitally corrected transposition of the great arteries (ccTGA) is generally considered favorable; however, the long-term outcome is the greatest problem, especially with regard to right ventricular (RV) function and tricuspid regurgitation (TR). Although tricuspid valve replacement (TVR) appears to be a realistic choice for treating severe TR, determining the timing of TVR may be difficult., Methods: We carried out a retrospective analysis of the long-term outcomes of physiologic repair for ccTGA focusing on patients with TVR. The study involved 23 patients after physiologic repair 10 or more years prior. There were 9 TVR cases in 5 pediatric patients (before age 18) and 4 adult patients., Results: There were two late deaths; however, there was no case related with cardiac events. Overall survival at 10 and 20 years were 95.5 and 90.2 %, respectively, and 7 of 8 patients after TVR were NYHA class I or II. No patient has presented postoperative complications in the form of bleeding or embolism after TVR with mechanical valve., Conclusions: An analysis of the results of physiologic repair for ccTGA showed that the long-term outcome was overall favorable. To maintain RV function, early TVR may be a reasonable option, even in the management of patients during childhood.

Objective: We study the validity of surgical procedure for total aortic arch replacement according to the atherosclerosis in the aortic arch., Methods: From 2007 to June 2013, Consecutive 185 patients underwent total aortic arch replacement for thoracic aortic anuerysm. We studied 135 patients[96 males 72.1 year(38~89year)]except emergency operation. We assessed the atherosclerosis in the aortic arch by preoperative enhanced computed tomography (CT)scan and intraoperative epiaortic echocardiography. Based on the degree of atherosclerosis in the aortic arch, we divided into 2 groups:group 1(G1)included 97 patients with mild or moderate atherosclerosis and group 2 (G2) 38 patients with severe atherosclerosis. We used ascending aorta as arterial cannulation site in G1 and axillary artery with 8 mm graft in G2 .We compared with both groups for preoperative comorbidities and outcomes( mortality and stroke)., Results: Three patients died in the hospital (2%). In-hospital neurological events occurred in 12 patients, including major stroke in 4 patients, minor stroke in 4 patients and asymptomatic convulsion in 4 patients, although they were transient and clear before discharge except major stroke. There were no statistically significant differences in preoperative characteristics, cardiopulmonary bypass, brain protection, mortality, and neurological events between the 2 groups. There was a statistically difference in operation time( 388.8 minutes vs 448.5 minutes, p<0.01), intensive care unit( ICU) stay( 3.1 day vs 6.5 days, p<0.05) and hospital stay( 19.2 days vs 28.0 days, p<0.05)., Conclusions: We selected surgical procedure for total aortic arch replacement (TAR) according to atherosclerosis in the aortic arch. Although the rate of stroke was largely acceptable, we much need to be improved in prevention of stroke.

Purpose: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is closely associated with Epstein-Barr virus (EBV). To elucidate its pathogenetic role, we examined the expression profiles of EBV-encoded proteins, especially focusing on latent membrane protein 1 (LMP1)., Experimental Design: Immunohistochemistry was carried out using clinical samples from ENKL cases, which were diagnosed between 1996 and 2010 at our institution. We statistically assessed the correlation between LMP1 positivity and the clinicopathologic data and further examined phosphorylation status of NF-κB RelA and Akt in ENKL cell lines., Results: Most of the 30 examined cases showed pleomorphic morphology, natural killer cell immunophenotype, and a localized disease. Immunohistochemistry detected EBERs, but not EBNA2, in all cases. LMP1 and LMP2A were positive in 22 (73.3%) and 12 cases (40.0%), respectively. LMP1-positive cases tended to show a localized disease (P = 0.060, the Fisher exact test). Nuclear localization of phosphorylated RelA and detection of phosphorylated Akt were predominantly observed in LMP1-positive cases (P = 0.002 and P < 0.001, respectively, the Fisher exact test). RNA silencing experiments of LMP1 in Hank1 cells suggested a positive correlation between LMP1 expression and phosphorylation of RelA and Akt. With a median follow-up period of 26.7 months (range, 0.2-142.3 months), the 2.5-year overall survival rates for LMP1-positive and -negative cases were estimated at 78.3% and 12.5%, respectively (P = 0.001, log-rank test)., Conclusions: LMP1 expression shows correlations with phosphorylation of RelA and Akt and possibly has a favorable impact on clinical outcome in ENKL., (©2012 AACR.)

Introduction: Various conservative treatments for Peyronie's disease (PD) have been attempted over the years. Intralesional verapamil injection has been tested in prospective randomized studies, but the effect of this treatment seems insufficient. Nicardipine is a calcium antagonist alternative to verapamil and is reportedly more effective in vitro., Aim: The objective of our study was to evaluate the usefulness of intralesional nicardipine injection as a conservative treatment for PD in the transition period of acute and chronic phase., Methods: Eighty-six patients (age: 38-72 years, mean: 52) were enrolled in this study. A total of 74 patients were assigned randomly to nicardipine group (10 mg diluted in 10 mL of distilled water daily, N=37) and control group (10 mL of saline water, N=37). A total of six injections were administrated biweekly., Mean Outcome Measure: The subjects were assessed by International Index of Erectile Function (IIEF)-5 and international pain scale. The plaque size was measured by ultrasonography after 20 µg intracavernosal injection of alprostadil (prostaglandin E1). The penile curvature was also measured by taking a photograph at maximum rigidity., Results: A reduction of pain score was seen throughout the course of treatment in both groups with a significant difference between the nicardipine and control groups (multiple analysis of variance test, P=0.019). A significant improvement of IIEF-5 score occurred only in the nicardipine group at 48 weeks after the initiation of treatment (P<0.01). The plaque size was significantly reduced at 48 weeks only in the nicardipine group (12 points, P=0.0004 by paired t-test). The penile curvature was significantly improved in both groups (P<0.01) without significant difference between them (P=0.14). There were no severe side effects, such as hypotension or other cardiovascular events., Conclusion: Our findings indicate that intralesional nicardipine injection is clinically effective as a conservative treatment for PD in the transition period of acute and chronic phase., (© 2010 International Society for Sexual Medicine.)

A 45-year-old man: pointed out von Recklinghausen disease (following vR disease) in 18 years old. He had a checkup in a close inspection purpose of a duodenum tumor at our hospital. We diagnosis that the accessory papilla carcinoid, and Pancreas Divisum was doubted. Rocal resection of the accessory papilla was performed and picked out carcinoid of 7 mm size. In literatures searches, as for accessory papilla carcinoid, merger frequency of a papilla tumor was high in the example, and merged, vR disease of lymph node metastasis.

Background: Recent studies have revealed that bone marrow cell (BMC) transplantation is effective not only for myocardial infarction (MI), but also for dilated cardiomyopathy (DCM). However, the method of administering donor cells remains unknown, and may differ between MI and DCM. In the present study, intramyocardial (IM) injection and intravenous (IV) delivery of BMC were compared in each etiological model., Methods and Results: MI was induced in 72 mice and DCM in another 36 mice by doxorubicin. BMCs were administered IV or IM in an acute MI (AMI), old MI (OMI) or DCM model. In the AMI model, left ventricular (LV) remodeling was reduced in both the IM- and IV-groups, but only in the IM-group in the OMI model. In the DCM model, the LV dimension of the IV-group was smaller than that of the IM-group. Histological examination showed that green fluorescent protein (GFP) cells were equally distributed in the infarct area of the IV- and IM-groups in AMI, and in the IM-group in the OMI model. In the DCM model, GFP cells were diffusely scattered throughout the ventricular wall in the IV-group, but were confined to the injection site in the IM-group., Conclusions: In OMI, IM delivery of BMCs was more effective than IV; however, IV delivery was superior in DCM. Delivery route should be selected according to the etiology of heart disease to optimize the efficacy of BMC transplantation.

Background: To confirm the effectiveness of alternative antiandrogen therapy (AAT) in Japanese patients with prostate cancer relapse after first-line hormonal therapy., Methods: A total of 80 patients who had successive serum prostate-specific antigen (PSA) progression after first-line hormonal therapy (luteinizing hormone-releasing hormone agonist alone: 21 cases; combined antiandrogen blockade therapy: 59 cases) were enrolled. We evaluated the positive ratio of antiandrogen withdrawal syndrome (AWS), the PSA responses with second- and third-line AAT, and cause-specific survival in terms of the effectiveness of AAT., Results: The overall positive AWS ratio after first-line therapy was 33%, while that after second-line therapy was 7%. There was no correlation between the first-line PSA response and the positive AWS. Of the 10 positive and the 20 negative AWS cases, secondary antiandrogen administration was effective in 50% and 60% of cases, respectively. The positive PSA responders at second- and third-line therapy were 51% and 13%, respectively. For second-line therapy, the effective rates from steroidal to non-steroidal, from non-steroidal to non-steroidal antiandrogen, and from non-steroidal to steroidal were 83%, 43%, and 14%, respectively. The cause-specific survival of the second-line responders was significantly better than that of the non-responders., Conclusion: There was a substantial number of patients who found second-line AAT to be modestly effective. Flutamide was effective as an alternative antiandrogen for the patients' relapse treatment with bicalutamide in Japanese men.

Background: The usefulness of sustained-release erythropoietin for improving left ventricular (LV) function without polycythemia was evaluated in a rat chronic myocardial infarction model., Methods and Results: Four weeks after left coronary artery ligation, 50 Sprague-Dawley rats were assigned to 5 groups (n=10, each). Control group had a gelatin sheet (20x20 mm) containing saline applied to the infarct area, whereas the 4 treatment groups had gelatin sheets incorporating erythropoietin 0.1 U, 1 U, 10 U and 100 U, respectively. Endpoint measurements performed at 8 weeks after the coronary ligation revealed that the fractional area change was larger for erythropoietin 1 U and 10 U than in the other 3 groups. The LV end-systolic elastance and the time constant of isovolumic relaxation were better for erythropoietin 1 U and 10 U than in the other 3 groups. The density of vessels larger than 50 microm in diameter was the highest in the erythropoietin 1 U group. The number of red blood cells was significantly increased in groups receiving erythropoietin 10 U and 100 U., Conclusions: Gelatin hydrogel sheets incorporating 1 U erythropoietin improved LV function without inducing polycythemia in a rat chronic myocardial infarction model.

Background: Myoblast transplantation (Tx) is promising for the improvement of cardiac function in ischemic cardiomyopathy. Insulin-like growth factor-1 (IGF-1) has anti-apoptotic and angiogenic effects, and induces myocyte hypertrophy. Our hypothesis is that topical and slow-release IGF-1 enhances the efficacy of Tx through its multiple functions., Methods: Four weeks after coronary artery ligation, Lewis rats were divided into four groups: (1) IGF-1+Tx, injection of 6 x 10(6) myoblasts into the infarcted area with placement of an IGF-1-impregnated sheet on the left ventricular (LV) free wall; (2) Tx, Tx alone; (3) IGF-1, IGF-1 sheet alone; and (4) control. We measured cardiac function and performed immunohistochemical examinations., Results: At 4 weeks after treatment, LV diastolic dimension was the smallest, end-systolic elastance was the highest, and tau was the smallest in the IGF-1+Tx group. The graft volume in the IGF-1+Tx group was 3-fold larger than in the Tx group. One day after transplantation, TUNEL-positive donor cells were fewer in the IGF-1+Tx than in the Tx group. Western blot analysis demonstrated that the phosphorylation of Akt increased and the expression of Bax decreased in the transplanted area of IGF-1+Tx rats compared with Tx rats. The vascular density in the peri-infarcted area was larger in IGF-1+Tx than in Tx rats. The mean diameter of graft-derived myotubes was larger in IGF-1+Tx than in Tx animals., Conclusions: IGF-1 increases the graft volume and enhances the efficacy of Tx in the chronic myocardial infarction model due to its multiple effects of preventing apoptosis, inducing angiogenesis, and promoting myoblast growth.