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A 32-year-old male patient was initially diagnosed with fibrosing mediastinitis. The patient subsequently developed severe dyspnea and was further diagnosed with constrictive pericarditis due to the extent of fibrosing mediastinitis around the heart. Therefore, the patient underwent surgical resection of the fibrotic tissue in the anterior mediastinum including the pericardium and the pleura. Postoperative histological and immunohistochemical analyses revealed angiosarcoma. Seven years after the diagnosis, he is still alive. Herein, we report a case of atypical primary angiosarcoma of the anterior mediastinum causing constrictive pericarditis and restrictive pulmonary dysfunction.

BACKGROUND In patients with severe coronary artery disease (CAD) requiring coronary revascularization, the prevalence of surgical ineligibility and its clinical effect on long-term outcomes remain unclear.Methods and Results:Among 15,939 patients with first coronary revascularization in the CREDO-Kyoto percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) registry cohort-2, we identified 3,982 patients with triple-vessel or left main disease (PCI: n=2,188, and CABG: n=1,794). Surgical ineligibility as documented in hospital charts was present in 142 (6.5%) of 2,188 PCI-patients, which was mainly related to comorbidities and advanced age. The cumulative 5-year incidence of the primary outcome measure (all-cause death/myocardial infarction/stroke) was much higher in PCI-patients with surgical ineligibility than in PCI-patients without surgical ineligibility and in CABG-patients (52.5%, 27.6%, and 24.0%, respectively, log-rank P

A 40-year-old male with Becker muscular dystrophy presented with severe mitral regurgitation and underwent mitral valve repair. Following the surgery, the patient became tachycardic, and developed a continuous high grade-fever and hyperbilirubinemia. The patient's condition worsened and we eventually tested his thyroid levels and discovered abnormally high thyroid levels. After diagnosing a severe thyroid storm, the patient was treated with oral administration of Lugol's iodine and thiamazole, as well as an intravenous steroid, which led to an immediate improvement of symptoms. The incidence of thyroid storm after open-heart surgery is extremely rare but highly life-threatening if unrecognized.

Background Staphylococcus lugdunensis is a coagulase-negative Staphylococcus species, which are weak pathogenic bacteria generally. However, the acute and severe pathogenicity of Staphylococcus lugdunensis infective endocarditis may be due to the rapid growth of large vegetation and consequent valve destruction. Case presentation The patient was an 81-year-old male who visited our hospital with chief complaints of low back pain and high fever. Four years before this visit, he had undergone aortic valve replacement for aortic regurgitation. He was found to be hypotensive. Although there is no heart murmur on auscultation and echocardiography revealed negative findings with aortic valve, a blood test showed increases in the white blood cell count and C-reactive protein concentration. On the next day, Gram-positive cocci were detected in a blood culture and echocardiography detected a large vegetation on the prosthetic valve with increased flow velocity. Therefore, he underwent redo aortic valve replacement emergently. Staphylococcus lugdunensis was identified in blood samples and vegetation culture. Consequently, the patient was treated with antibiotics for 5 weeks after the operation and discharged home. Conclusions We experienced rapidly progressive prosthetic valve endocarditis caused by Staphylococcus lugdunensis. Hence, Staphylococcus lugdunensis infective endocarditis requires aggressive treatment, and the pathogenicity of this coagulase-negative Staphylococcus with high drug susceptibility should not be underestimated.

Objective Most randomized controlled trials of off-pump versus on-pump coronary artery bypass grafting (CABG) have included limited numbers of patients with preoperative renal failure. This study was performed to evaluate the association between the clinical benefit of the off-pump technique and chronic kidney disease (CKD) stage. Methods We analyzed 38,051 patients with CKD who underwent primary non-emergent isolated CABG from 2013 to 2015 as reported in the Japan Cardiovascular Surgery Database-Adult section. These patients were stratified into four categories according to their estimated glomerular filtration rate (eGFR), expressed in ml/min per 1.73 m 2 : eGFR of 60–90, 30–59, and Results In total, 23,634 (62.1%) patients were intended for off-pump CABG. In patients with mildly reduced renal function (eGFR of 60–89), there was no significant risk reduction effect of off-pump CABG for operative mortality. Conversely, in patients with moderate or severe renal disease (eGFR of Conclusion The off-pump technique significantly reduced operative mortality in patients with moderate or severe preoperative renal dysfunction.

Background The contemporary medications for secondary prevention like statins and antithrombotic agents are targeting to delay the progression of atherothrombosis. However, there is limited data on the relation between death and progressive coronary atherothrombosis. This study sought to evaluate what proportion of death after coronary revascularization is related to documented progressive coronary atherothrombosis. Methods We reviewed the detailed causes of death among 15,231 patients receiving their first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2, dividing into two groups; 13,839 patients with clinical success and without major complication (uncomplicated) and the other 1392 patients (complicated). Documented progressive coronary atherothrombosis as the cause of death was defined as preceding coronary revascularization within 30 days before death or irreversible brain damage and/or proof of coronary thrombus by autopsy. Results During the median follow-up of 5.4 years, 2837 patients died with cumulative 5-year incidence of 17.5%. The proportions of cardiac/non-cardiovascular death among all-cause death in uncomplicated patients and complicated patients were 36.6%/51.5% and 74.2%/17.4%, respectively. The numbers of patients died with documented progressive coronary atherothrombosis were 41 (1.9% of all-cause death) and 304 (47.3%). The number was only 51 (2.1%) among all post-discharge patients. Dominant causes of cardiac death in post-discharge patients included heart failure (10.0%) and sudden cardiac death (9.1%), both without apparent relation with progressive coronary atherothrombosis. Conclusions Only about one-third of deaths were cardiac in origin during 5-year follow-up in post-discharge patients after coronary revascularization. Cardiac death after discharge was very infrequently related to documented progressive coronary atherothrombosis.

OBJECTIVES Little data are available with regard to valve selections in redo valvular surgery. We investigated the impact of valve types on late outcomes after redo mitral valve replacement (MVR). METHODS We retrospectively reviewed 66 patients aged 50-69 (mean age 62.2 ± 5.1) years who underwent redo MVR over the past 25 years. In redo MVR, 46 (69.7%) redo procedures were the 1st redo valvular surgeries, 16 (24.2%) were 2nd redos, 3 (4.5%) were 3rd redos and 1 was a 4th (1.5%) redo. We classified 66 patients into 2 groups: mechanical MVR group (M-MVR, n = 44) and biological MVR group (B-MVR, n = 22). The mean follow-up period was 8.2 ± 6.3 years. RESULTS Hospital mortality rates were 3.3% in M-MVR and 9.7% in B-MVR (P = 0.3328). Survival rates in M-MVR and B-MVR at 5 and 10 years were 93.0 ± 4.8% vs 76.0 ± 10.5% and 77.6 ± 9.1% vs 51.3 ± 13.7%, respectively (log-rank test, P = 0.0072). Late death occurred in 7 patients in M-MVR and 9 in B-MVR. Freedom rates from valve-related events in M-MVR and B-MVR at 5 and 10 years were 100.0 ± 0.0% vs 76.5 ± 10.3% and 93.3 ± 6.4% vs 52.4 ± 13.6%, respectively (log-rank test, P

Aim We reviewed our experience in redo valvular surgery to evaluate trends in short- and long-term outcomes. Methods We reviewed 414 patients (mean age, 62.8 ± 13.6 years) who underwent redo valvular surgery in the past 25 years. A total of 301 patients (54.2%) underwent first-time redo valvular surgeries; 178 (32.1%) were second redos, 60 (10.8%) were third redos, and 16 were fourth redos (2.9%). The mean follow-up period was 6.8 ± 6.3 years. Results Hospital mortality was 5.8%. New York Heart Association (NYHA) class III/IV (P = 0.0007, odds ratio = 4.403) and hemodialysis (P = 0.0383, odds ratio = 7.196) were risk factors for hospital death. Long-term survival rates at 15 and 20 years were 64.7% ± 4.3% and 59.1% ± 5.0%, respectively. Predictors of late death were first time redo (P = 0.0076, hazard ratio = 0.422) and age younger than 61 years (P = 0.0005, hazard ratio = 0.229). There were significant differences in long-term survival between NYHA classes I/II and III/IV (log-rank test, P = 0.0419) and between the time from redo surgery (log-rank test, P = 0.0189) and age (log-rank test, P = 0.0001). Conclusions The hospital mortality rate for redo valve surgery has improved. Early referral for redo surgery can contribute to improving early and late outcomes.

Torsade de Pointes (TdP) is a lethal arrhythmia that is often drug-induced, thus there is an urgent need for development of models to test or predict the drug sensitivity of human cardiac tissue. Here, we present an in vitro TdP model using 3D cardiac tissue sheets (CTSs) that contain a mixture of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and non-myocytes. We simultaneously monitor the extracellular field potential (EFP) and the contractile movement of the CTSs. Upon treatment with IKr channel blockers, CTSs exhibit tachyarrhythmias with characteristics of TdP, including both a typical polymorphic EFP and meandering spiral wave re-entry. The TdP-like waveform is predominantly observed in CTSs with the cell mixture, indicating that cellular heterogeneity and the multi-layered 3D structure are both essential factors for reproducing TdP-like arrhythmias in vitro. This 3D model could provide the mechanistic detail underlying TdP generation and means for drug discovery and safety tests., ヒトiPS細胞から3次元的な心臓組織を作製し、致死性不整脈の複雑な特徴を培養下に再現することに成功. 京都大学プレスリリース. 2017-10-25.

Objectives Although conventional open repair is our preference for patients with aortic arch aneurysms, we have often chosen thoracic endovascular aneurysm repair (TEVAR) with a handmade branched stent graft (bTEVAR) in high-risk patients. The aim of this study was to compare the midterm clinical outcomes of our bTEVAR technique to those of the open repair. Methods Between January 2007 and December 2014, we treated 129 patients with aortic arch aneurysm by means of either conventional open repair (OPEN, n = 61) or bTEVAR (n = 68) at our institution. Results The mean ages were 70.5 ± 12.7 years in the OPEN group and 72.7 ± 12.5 years in the bTEVAR group (P = 0.32). The aetiologies included true aneurysm in 101 patients (78.3%) and chronic dissection in 26 (20.1%). There were 2 (3.3%) in-hospital deaths in the OPEN group and 3 (4.4%) in the bTEVAR group. The mean follow-up duration was 3.0 ± 2.1 years (2.4 ± 1.9 years in the OPEN group and 3.6 ± 2.3 years in the bTEVAR group). There was no difference in 5-year aneurysm-related mortality between groups (10.7% in OPEN vs 12.8% in bTEVAR, P = 0.50). In terms of late additional procedures, however, none were required in the OPEN group, whereas 10 (15.4%) additional endovascular repairs and 4 (6.2%) open repairs were required in the bTEVAR group. Conclusions Our bTEVAR could be performed with low early mortality, and it yielded similar midterm aneurysm-related mortality to that of conventional open repair. However, these patients undergoing this technique required more late additional procedures than those undergoing conventional open repair.

Background:There is discordance regarding the effect of symptom status before aortic valve replacement (AVR) on long-term outcome after AVR in severe aortic stenosis (AS). Methods and Results:The CURRENT AS registry is a multicenter retrospective registry enrolling 3, 815 consecutive patients with severe AS. Among 1, 196 patients managed with the initial AVR strategy, long-term clinical outcomes were compared between the symptomatic patients (n=905), and asymptomatic patients (n=291). Median follow-up interval was 1337 days with a 91% follow-up rate at 2 years. AVR was performed in 886 patients (98%) in the symptomatic group and in 287 patients (99%) in the asymptomatic group. Symptomatic patients were older and more often had comorbidities than asymptomatic patients with similar echocardiographic AS severity. The cumulative 5-year incidences of all-cause death and heart failure (HF) hospitalization were significantly higher in symptomatic patients than in asymptomatic patients (25.6% vs. 15.4%, P=0.001, and 14.2% vs. 3.8%, P

Background Systemic inflammation after prolonged cardiopulmonary bypass (CPB) can cause serious multiorgan system dysfunction. Mesenchymal stem cells (MSCs) are reported to reduce inflammation and attenuate immune response. We have focused on fetal membrane (FM) as a source to provide a large number of MSCs (FM-MSCs). Allogeneic administration of FM-MSCs has been reported to mitigate autoimmune myocarditis or glomerulonephritis. The aim of this study was to investigate whether allogeneic FM-MSCs attenuate systemic inflammatory responses and lung injury in a rat CPB model. Methods Male Lewis rats (major histocompatibility complex haplotype: RT-1l) were divided randomly into 3 groups (n = 7 each): cannulation alone (sham group), CPB alone (control group), and CPB + MSC (MSC group). An experimental rat CPB model was established, and CPB was maintained for 30 minutes. In the MSC group, MSCs (1 × 10 6 cells) derived from the FM of ACI rats with a different major histocompatibility complex haplotype (RT-1a) were administrated intravenously before CPB initiation. Results Serum concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1β in the MSC group were significantly lower compared with the control group after CPB. Similarly, mRNA expression of proinflammatory cytokines in the lung was lower in the MSC group. Allogeneic administration of FM-MSCs remarkably decreased the lung injury score, protected alveolar structure, inhibited neutrophil infiltration to the lung interstitium, and stimulated cytoprotective cytokine production in the lung. Conclusions Allogeneic transplantation of FM-MSCs may be a potent strategy to prevent CPB-induced systemic inflammation and acute lung injury by suppressing the expression of inflammatory cytokines and promoting protective factors in the lung.

Although transcatheter aortic valve replacement (TAVR) is an excellent alternative procedure for high-risk patients with severe symptomatic aortic stenosis, it is often associated with life-threatening complications. We report on the emergency or elective use of veno-arterial extracorporeal membrane oxygenation (ECMO) to manage these complications. Between December 2013 and February 2016, 46 patients underwent TAVR at our institution. Of these, 4 patients required emergency ECMO support and another 3 patients were electively placed on ECMO support at the start of the procedure. The mean age of the ECMO patients was 87.3 ± 3.6 years and all were female. The Society of Thoracic Surgeons-predicted risk of mortality score in these patients was 12.2 ± 6.2%. TAVR with ECMO was completed through the transapical approach in 6 patients, and the transfemoral approach in 1 patient. The arterial access route for ECMO was the femoral artery in 5, the external iliac artery in 1, and the subclavian artery in 1. Indications for the use of emergency ECMO were hemodynamic instability in 2, cardiogenic shock in 2, while indications for elective ECMO were severe pulmonary hypertension, impaired left ventricular function and a combination of these. There was no 30-day mortality, and the 1-year survival rate was 83.3% with no significant difference compared to patients without ECMO support. The use of ECMO in very high-risk patients undergoing TAVR may increase safety and contribute to excellent outcomes. Although ECMO support is rarely needed in TAVR, a well-prepared treatment strategy by the heart team is mandatory.

Background The ACC/AHA guidelines introduced a new classification of severe aortic stenosis (AS) mainly based on maximum jet velocity (Vmax) and mean pressure gradient (mPG), but not on aortic valve area (AVA). However, prognostic value of this new classification has not yet been fully evaluated. Methods and results We studied 1512 patients with asymptomatic severe AS enrolled in the CURRENT AS registry in whom surgery was not initially planned. Patients were divided into 2 groups: Group 1 (N=122) comprised patients who met the recommendation for surgery; high-gradient (HG)-AS (Vmax≥4.0m/s or mPG≥40mmHg) with ejection fraction (EF) 2 (N=892). The excess risk of Group 1 relative to Group 2 for the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significant (adjusted HR: 1.92, 95%CI: 1.37–2.68, P Conclusion Trans-aortic valve gradient in combination with EF was a good prognostic marker in patients with asymptomatic AS. However, patients with LGrEF-AS had extremely poor prognosis when managed conservatively.

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P, See Editorial by Tribouilloy et al

Background Tricuspid valve regurgitation due to pacemaker leads is a well-known complication. Although some reports have suggested that pacemaker leads should be surgically explanted, strongly adhered leads cannot always be removed. The aim of this study was to describe our tricuspid valve repair techniques with pacemaker leads left in situ. Methods Our retrospective study investigated 6 consecutive patients who required tricuspid valve surgery for severe regurgitation induced by pacemaker leads. Results From the operative findings, we identified 3 patterns of tricuspid valve and pacemaker lead involvement. In 3 patients, the leads were caught in the chordae, in 2 patients, tricuspid regurgitation was caused by lead impingement on the septal leaflet, and in 3 patients, tricuspid valve leaflets had been perforated by the pacemaker leads. During surgery, all leads were left in situ after being separated from the leaflet or valvular apparatus. In addition, suture annuloplasty was performed for annular dilatation in all cases. In one patient, the lead was reaffixed to the annulus after the posterior leaflet was cut back towards the annulus, and the leaflet was then closed. There was one hospital death due to sepsis. The degree of tricuspid regurgitation was trivial in all surviving patients at discharge. During a mean follow-up of 21 months, one patient died from pneumonia 20 months after tricuspid valve repair. Conclusion In patients undergoing tricuspid valve surgery due to severe tricuspid regurgitation caused by pacemaker leads, the leads can be left in situ after proper repair with annuloplasty.

Acute kidney injury (AKI) is a common complication accompanying cardiopulmonary bypass (CPB) and is independently associated with increased morbidity and death. Diabetes mellitus increases the risk for AKI after CPB. Epigallocatechin-3-gallate (EGCG) is a major component of the polyphenolic fraction of green tea, which possesses cardioprotective activities, as previously reported. We hypothesized that EGCG also possesses a renoprotective effect through its diverse biochemical properties and assessed the effect on renal function after CPB for diabetic rats.Goto-Kakizaki rats developing type 2 diabetes mellitus were randomly assigned to one of the following groups: sham (n = 10), CPB (CPB alone, n = 9), or EGCG (CPB + EGCG, n = 10). CPB was conducted for 30 minutes at a flow rate of 100 mL/kg/min in the CPB and EGCG groups. Rats assigned to the EGCG group were administrated EGCG solution orally for 2 weeks before CPB. We evaluated renal biochemical or histologic changes at 24 hours after CPB.Compared with the CPB group, the EGCG group exhibited milder tubular injury histologically (p0.0001) and reduced expression of kidney injury molecule-1, a biomarker for renal tubular injury (p0.0001) and 8-hydroxy-2'-deoxyguanosine (p0.01), indicating attenuated oxidant stress.Preoperative oral administration of EGCG ameliorates AKI in a CPB model of diabetic rats through antioxidative properties. This simple method could be applied in a clinical setting as a prophylactic renal protection against AKI after CPB, especially for high-risk patients with diabetes mellitus.

A 12-month-old microminipig, weighing 12.6 kg, showed 3 repeated episodes of transient ST-segment elevation in 24 hr Holter electrocardiogram after placing an ameroid constrictor around the left anterior descending coronary artery. Ventricular fibrillation was noticed just after the cessation of the 24 hr Holter-electrocardiogram recording. Direct current defibrillations and cardiopulmonary resuscitation were performed; however, they were unsuccessful, leading to the animal's death. Its heart was excised for macroscopic analysis, which indicated that lumen of the ameroid constrictor was not narrowed and that there was no dissection, embolus or thrombus in the coronary arteries, indirectly suggesting that coronary artery vasospasm may have caused the ischemic attacks. Thus, microminipig may possess some potential to have coronary vasospasm.

To realize human induced pluripotent stem cell (hiPSC)-based cardiac regenerative therapy, evidence of therapeutic advantages in human-sized diseased hearts are indispensable. In combination with an efficient and simultaneous differentiation of various cardiac lineages from hiPSCs and cell sheet technology, we aimed to generate clinical-sized large cardiac tissue sheets (L-CTSs) and to evaluate the therapeutic potential in porcine infarct heart. We simultaneously induced cardiomyocytes (CMs) and vascular cells [vascular endothelial cells (ECs) and vascular mural cells (MCs)] from hiPSCs. We generated L-CTSs using 10cm-sized temperature-responsive culture dishes. We induced myocardial infarction (MI) in micromini-pigs (15–25 kg) and transplanted the L-CTSs (Tx) 2 weeks after MI induction (4 sheets/recipient) under immunosuppression (Tx: n = 5, Sham: n = 5). Self-pulsating L-CTSs were approximately 3.5cm in diameter with 6.8×106±0.8 of cells containing cTnT+-CMs (45.6±13.2%), VE-cadherin+-ECs (5.3±4.4%) and PDGFRβ+-MCs (14.4±20.7%), respectively (n = 5). In Tx group, echocardiogram indicated a significantly higher systolic function of the left ventricle (LV) compared to that in sham control (Sham vs Tx: fractional shortening: 24.2±8.6 vs 40.5±9.7%; p

In Japan, transcatheter aortic valve implantation (TAVI) with Edwards-SAPIEN XT valve (Edwards Lifesciences Inc., Irvine, CA, USA) started in October 2013. All institutions should undergo a training period to perform TAVI independently. Balloon aortic valvuloplasty (BAV) as a bridge to TAVI during the training period should be performed with caution to avoid severe aortic regurgitation (AR) because bailout TAVI is not possible. We present a case in which BAV was successfully performed as a bridge to TAVI during the training period. The patient was an 85-year-old man with medically uncontrollable congestive heart failure due to severe aortic valve stenosis. The aortic valve area was 0.60cm2 with a left ventricular ejection fraction of 20%. TAVI was considered a safe but high-risk strategy owing to the unstable hemodynamic condition. We chose BAV as a bridge therapy to TAVI. The aortic annulus diameter was 25.3mm on computed tomography scans. We chose a 20-mm balloon catheter to avoid BAV-induced AR. Transfemoral TAVI was performed successfully 16 days after BAV using a 26-mm SAPIEN XT valve. The postoperative course was uneventful. The case demonstrated BAV as a bridge therapy to TAVI can be safely and effectively performed during the training period.

Hemodialysis patients have an increased risk of hemorrhage compared to other patients. This study reports the frequencies of hemorrhage and its impact on the survival of hemodialysis patients after valve replacement. A total of 77 consecutive dialysis patients who underwent prosthetic valve surgery from 1991 to 2011 were retrospectively reviewed. Their mean age was 65.8 ± 9.2 years. Forty-three patients (56 %) were male. Fifty-nine patients (77 %) had aortic valve replacement, and 23 patients (30 %) had mitral valve replacement. Bioprosthetic valves were used in 17 patients (22 %). There were seven in-hospital mortalities (9.1 %). The overall estimated Kaplan–Meier survival after 3, 5 and 7 years was 66.6 ± 5.6, 51.1 ± 6.3 and 34.4 ± 6.8 %, respectively. Seventeen (22 %) bleeding events were observed (5.9 % per patient-years) in the follow-up period. Six of the nine patients with cerebral hemorrhages and two of the six with gastrointestinal hemorrhages died. There were no differences in the frequencies of hemorrhage between the patients treated with bioprostheses and mechanical valves. This study found that 22 % of dialysis patients had hemorrhagic events after valve replacement, and approximately half of them died. Particularly, cerebral hemorrhage was fatal and two thirds of the patients died. So we should meditate the methods to reduce hemorrhage. Therefore, new methods to reduce the risk of hemorrhage are urgently needed.

We investigated the impact of diabetes mellitus on long-term outcomes of percutaneous coronary intervention (PCI) in the drug-eluting stent era versus coronary artery bypass grafting (CABG) in a real-world population with advanced coronary disease. We identified 3,982 patients with 3-vessel and/or left main disease of 15,939 patients with first coronary revascularization enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2 (patients without diabetes: n = 1,984 [PCI: n = 1,123 and CABG: n = 861], and patients with diabetes: n = 1,998 [PCI: n = 1,065 and CABG: n = 933]). Cumulative 5-year incidence of all-cause death after PCI was significantly higher than after CABG both in patients without and with diabetes (19.8% vs 16.2%, p = 0.01, and 22.9% vs 19.0%, p = 0.046, respectively). After adjusting confounders, the excess mortality risk of PCI relative to CABG was no longer significant (hazard ratio [HR] 1.16; 95% confidence interval [CI] 0.88 to 1.54; p = 0.29) in patients without diabetes, whereas it remained significant (HR 1.31; 95% CI 1.01 to 1.70; p = 0.04) in patients with diabetes. The excess adjusted risks of PCI relative to CABG for cardiac death, myocardial infarction (MI), and any coronary revascularization were significant in both patients without (HR 1.59, 95% CI 1.01 to 2.51, p = 0.047; HR 2.16, 95% CI 1.20 to 3.87, p = 0.01; and HR 3.30, 95% CI 2.55 to 4.25, p0.001, respectively) and with diabetes (HR 1.45, 95% CI 1.00 to 2.51, p = 0.047; HR 2.31, 95% CI 1.31 to 4.08, p = 0.004; and HR 3.70, 95% CI 2.91 to 4.69, p0.001, respectively). There was no interaction between diabetic status and the effect of PCI relative to CABG for all-cause death, cardiac death, MI, and any revascularization. In conclusion, in both patients without and with diabetes with 3-vessel and/or left main disease, CABG compared with PCI was associated with better 5-year outcomes in terms of cardiac death, MI, and any coronary revascularization. There was no difference in the direction and magnitude of treatment effect of CABG relative to PCI regardless of diabetic status.

Background We sought to assess the long-term durability of pericardial valves in patients at age

Background Bioprostheses have become increasingly popular for aortic valve replacement (AVR) in recent years, but mechanical valves are still the standard choice, especially for younger patients. The aim of this study was to assess the very long-term outcomes in Japanese patients who underwent AVR with St. Jude Medical (SJM) mechanical valves. Methods and results From 1991 to 2001, a total of 816 patients underwent AVR with SJM mechanical valves in 5 hospitals. Of these, 801 patients (mean age, 58.3±11.7 years) were analyzed in this study. There were 24 in-hospital deaths (3.0%). Mean follow-up duration was 11.6±6.7 years and the 10-year follow-up rate was 84.1%. Freedom from valve-related death at 5, 10, 15, and 20 years was 96.2%, 92.7%, 88.8%, and 86.6%, respectively. The linearized ratio of major bleeding events and thromboembolic events was 1.1% per patient-year and 1.0% per patient-year, respectively. Freedom from reoperation for the aortic prosthesis was 98.0% and 94.8% at 10 and 20 years, respectively. Conclusions The SJM mechanical valve provided excellent long-term freedom from valve-related death and reoperation in patients undergoing AVR. Therefore, this valve should be recommended to younger patients who wish to avoid reoperation.

This study investigated the safety and efficacy of a sustained release of basic fibroblast growth factor (bFGF) with biodegradable gelatin hydrogel sheets as therapeutic angiogenesis in canine chronic myocardial infarction (MI) models. Canine chronic MI model was induced by ligating the left anterior descending coronary artery and its diagonal branches. At 4 week post-induction, we applied either saline (Control group, n = 5) or 200 μg of bFGF (Treatment group, n = 6) soaked gelatin hydrogel sheets on the ischemic area of the left ventricular (LV) wall. At 6 weeks after the procedure, we evaluated the efficacy by echocardiography and immunohistochemical study. There were no procedure-related adverse events or deaths. The serum bFGF level was under detectable levels in all animals at any sampling points. In terms of efficacy, echocardiographic evaluation demonstrated that fractional shortening was significantly improved in the treatment group. In addition, immunohistochemical study showed that the capillary density in the border zone of the MI area, as well as the MI area, significantly increased in the treatment group. Therapeutic angiogenesis by bFGF using biodegradable gelatin hydrogel sheets was safe, increased the capillary density, and improved LV function in canine chronic MI models.

Whether patients with severe aortic stenosis (AS) die because of AS-related causes is an important issue for the management of these patients. We used data from CURRENT AS registry, a Japanese multicenter registry, to assess the causes of death in severe AS patients and to identify the factors associated with non-cardiac mortality. We enrolled 3815 consecutive patients with a median follow-up of 1176 days; the 1449 overall deaths comprised 802 (55.3%) from cardiac and 647 (44.7%) from non-cardiac causes. Heart failure (HF) (25.7%) and sudden death (13.0%) caused the most cardiac deaths, whereas infection (13.0%) and malignancy (11.1%) were the main non-cardiac causes. According to treatment strategies, infection was the most common cause of non-cardiac death, followed by malignancy, in both the initial aortic valve replacement (AVR) cohort (N = 1197), and the conservative management cohort (N = 2618). Both non-cardiac factors (age, male, body mass index

The aim of this study was to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) in patients with severe aortic stenosis (AS).The prognostic impact of LVEF in severe AS remains controversial.Among 3,815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study population consisted of 3,794 patients after excluding 21 patients without LVEF data. Patients were divided into 4 groups according to LVEF at index echocardiography (50%, 50% to 59%, 60% to 69%, and ≥70%; conservative strategy: n = 388, n = 390, n = 1,025, and n = 800; initial aortic valve replacement strategy: n = 206, n = 170, n = 375, and n = 440). Echocardiographic data were site reported, and there was no echocardiography core laboratory.In the conservative group, the cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significantly higher in patients with LVEFs 50% and 50% to 59% than in those with LVEFs 60% to 69% and ≥70% (72.3%, 58.4%, 38.7%, and 35.0%, respectively, p 0.001), whereas in the initial aortic valve replacement group, the negative effect of low LVEF was markedly attenuated (20.2%, 20.3%, 17.7%, and 12.4%, respectively, p = 0.03). After adjusting for confounders, LVEF 50% (hazard ratio: 1.82; 95% confidence interval: 1.44 to 2.28; p 0.001) and 50% to 59% (hazard ratio: 1.77; 95% confidence interval: 1.42 to 2.20; p 0.001) but not 60% to 69% (hazard ratio: 1.14; 95% confidence interval: 0.94 to 1.39; p = 0.17) were independently associated with poorer outcomes compared with LVEF ≥70% (reference) in the conservative group. In the initial aortic valve replacement group, the adjusted risk for the primary outcome measure was not significantly different across the 4 LVEF groups.This study demonstrates that survival in patients with severe AS is impaired when LVEF is 60%, and these findings have implications for decision making with regard to the timing of surgical intervention.

Background There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis ( AS ). Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax AS ‐related events (aortic valve–related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P P =0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P =0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS ‐related events remained significant (hazard ratio, 1.39; 95% CI , 1.07–1.81; P =0.02, and hazard ratio, 1.53; 95% CI , 1.17–2.00; P =0.002, respectively). The effect size of group 3 relative to group 1 for AS ‐related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI , 1.01–2.52; P =0.047, and hazard ratio, 1.67; 95% CI , 1.16–2.40, P =0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS ‐related events (interaction, P =0.88). Conclusions In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS ‐related events. However, the cumulative 5‐year incidence of the AS ‐related events remained very high even in asymptomatic patients with less greater Vmax.

Recent studies demonstrate that microRNAs show promising potential, including angiogenesis, in therapeutic intervention. MicroRNA-126 (miR-126) is reported to regulate angiogenesis by blocking Sprouty-related EVH1 domain-containing protein 1 (SPRED1), an endogenous inhibitor of vascular endothelial cell growth factor. In this study, we investigated the angiogenic effects of the sustained release of miR-126 loaded with poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) in a murine hindlimb ischemia model.We induced mice hindlimb ischemia through femoral artery excision. We randomly assigned the mice to two groups and performed an intramuscular injection of miR-126-loaded PLGA NPs (miR-126) or scrambled miR-loaded PLGA NPs (control) shortly after induction of ischemia.The miR-126 expression levels in the ischemic limb at 3 days after treatment were significantly higher in mice treated with miR-126-loaded PLGA NPs than in those with scrambled miR, indicating the fair efficiency of local miR transduction (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P .05; n = 6). Laser Doppler perfusion imaging revealed that limb blood flow in mice treated with miR-126-loaded PLGA NPs was significantly higher at 14 days after treatment (sham vs control vs miR-126: 0.62 ± 0.09 vs 0.58 ± 0.05 vs 0.72 ± 0.07; P .001; n = 12). Immunohistochemical analysis indicated that CD31-positive cell density and α-smooth muscle actin-positive vessel density were significantly higher in miR-126-treated mice (control vs miR-126: 0.33 ± 0.12 vs 0.74 ± 0.42; P .05; n = 6). SPRED1 messenger RNA expression levels were significantly lower in miR-126-treated mice (control vs miR-126: 1.00 ± 0.05 vs 0.81 ± 0.07; P .05; n = 6). Western blotting indicated that protein levels of pERK/ERK mediated by SPRED1 were significantly higher in miR-126-treated mice (control vs miR-126: 0.29 ± 0.10 vs 0.54 ± 0.21; P .05; n = 6).This study suggests that sustained release of miR-126-loaded PLGA NPs might be an effective method in therapeutic angiogenesis for hindlimb ischemia.

BACKGROUND The aim of this study was to assess the long-term outcomes of aortic valve replacement (AVR) with either mechanical or bioprosthetic valves according to age at operation.Methods and Results:A total of 1,002 patients (527 mechanical valves and 475 bioprosthetic valves) undergoing first-time AVR were categorized according to age at operation: group Y, age

The current study describes a scalable, porous large-format engineered cardiac tissue (LF-ECT) composed of human induced pluripotent stem cells (hiPSCs) derived multiple lineage cardiac cells with varied 3D geometries and cell densities developed towards the goal of scale-up for large animal pre-clinical studies. We explored multiple 15 × 15 mm ECT geometries using molds with rectangular internal staggered posts (mesh, ME), without posts (plain sheet, PS), or long parallel posts (multiple linear bundles, ML) and a gel matrix containing hiPSC-derived cardiomyocytes, endothelial, and vascular mural cells matured in vitro for 14 days. ME-ECTs displayed the lowest dead cell ratio (p

A 50-year-old man was admitted with fever and chill sensation 6 months ago. Transthoracic echocardiography (TTE) showed left and right coronary cusp prolapses and a thickened tissue of the aortic curtain. Congestive heart failure due to active infective aortic valve endocarditis was diagnosed, and he underwent aortic valve replacement. The aortic annulus was reconstructed using a glutaraldehydetreated autologous pericardium. Six months after surgery, TTE showed severe aortic regurgitation and saccular change in the aortic annulus. Transesophageal echocargiography showed some echo free space from left to noncoronary cusp and abnormal movement of the prosthetic valve annulus. Intraoperative examination showed dehiscence of the pericardial patch from the aortic wall, but no finding of infection. Aortic valve rereplacement was performed with reconstruction of the aortic annulus using a bovine pericardium. To prevent the dehiscence of the pericardial patch from the aortic wall, sutures fixing the prosthetic valve were passed from outside of the aortic wall.

SummaryWhat is known and objective Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. METHODS From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. RESULTS The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P

OBJECTIVES: The optimal strategy for coronary revascularization in patients with renal dysfunction remains undefined. As coronary artery bypass grafting (CABG) may be associated with higher mortality, less invasive percutaneous coronary intervention (PCI) may be preferred. To date, only limited information has been published regarding the effects of severe renal dysfunction on the outcome after CABG and PCI. To address this limitation, we analysed the clinical outcomes after CABG or PCI in patients with severe renal dysfunction not on chronic haemodialysis (HD). METHODS: Among patients enrolled in the CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) Registry (a multicentre PCI/CABG registry in Japan), we identified 374 patients with multivessel disease and an estimated glomerular filtration rate