[Reconstruction of Anterior Mitral Leaflet Using Fresh Autologous Pericardial Patch for Active Infective Endocarditis;Report of a Case].

Several reports have described that the prognosis of patients with mitral valve regurgitation due to active infective endocarditis (IE) is better after mitral valve plasty (MVP) than replacement (MVR). However, extensive destruction of valve tissue might cause difficulties with MVP. We repaired a widely-affected anterior mitral leaflet (AML) using an autologous pericardial patch. A 44-year-old woman with mitral regurgitation presented with prolonged fever and backache. We made a diagnosis of active IE accompanied by mitral valve regurgitation. We performed MVP, widely resected the infected areas of the AML, and reconstructed the defective area using the pericardial patch. She was discharged after four weeks of antibiotic therapy, when she was free of recurrence. The pericardial patch facilitated MVP and was effective for treating mitral valve regurgitation due to active IE.

[Extracardiac Aorto-right Atrial Fistula after Aortic Valve Replacement].

The development of a fistula between the aorta and the right atrium is a relatively rare but well-documented complication after cardiac surgery and proximal aortic dissection, and has a high mortality rate if it is not diagnosed adequately and surgically treated without delay. We report a rare case of extracardiac aorta-right atrial fistula. An 86-year-old woman underwent aortic valve replacement via median sternotomy. Two weeks after surgery, the upper median skin incision reopened, which exposed the sternum and revealed purulent discharge inside the wound. Wound and blood cultures were positive for methicillin-resistant Staphylococcus aureus. The wound was treated, and healed in approximately 2 weeks. Six weeks after surgery, the patient suddenly presented with dyspnea because of heart failure.Extracardiac aorto-right atrial fistula was confirmed by computed tomography. During surgery, we found an extracardiac fistula formed in the hematoma between the sites where the aortic vent suture was tied and the caval cannula was removed. The infection seemed to have contributed to the development of the fistula and may have persisted in the ascending aorta or artificial valve, which may have led to cerebral hemorrhage resulting in death 4 months later.

Preoperative chronic kidney disease as a strong predictor of postoperative infection and mortality after coronary artery bypass grafting.

BACKGROUND: The aim of this study was to determine the influence of preoperative kidney dysfunction (ie, chronic kidney disease (CKD)) on postoperative cardiovascular events, infection, acute kidney injury and hospital mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: A multi-institutional retrospective study was performed at 14 hospitals of adult patients undergoing isolated CABG from 2007 to 2008 (n=1,522). We classified CKD level according to preoperative estimated glomerular filtration rate (eGFR): normal, eGFR >90 ml·min(-1)·1.73 m(-2); mild, eGFR 60-90 ml·min(-1)·1.73 m(-2); moderate, eGFR 30-59 ml·min(-1)·1.73 m(-2); and severe, eGFR <30 ml·min(-1)·1.73 m(-2), and assessed postoperative outcome. Preoperative CKD distribution was as follows: normal, n=121 (8%); mild, n=713 (47%); moderate, n=515 (34%); and severe, n=169 (11%). Risk of infection was strongly correlated with CKD level (normal, 3.3%; mild, 7.0%; moderate, 8.3%; severe, 17.0%; P<0.01). The risk of in-hospital death was also strongly correlated with CKD level (normal, 1.7%; mild, 1.0%; moderate, 1.6%; severe, 5.9%; P<0.01). On multivariate logistic regression analysis, CKD level was identified as a significant risk factor for postoperative infection, acute kidney injury, and in-hospital death. CONCLUSIONS: Advanced preoperative CKD is a strong predictor of postoperative infection, acute kidney injury and in-hospital death after CABG.

Cardiac Tamponade Due to Intrapericardial Hernia Mimicking ST-Segment Elevation Myocardial Infarction.

Intrapericardial hernia is a diaphragmatic hernia that extremely rarely causes cardiac tamponade. We present a case of a cardiac tamponade caused by an intrapericardial hernia in a 78-year-old male patient with a history of coronary artery bypass grafting, mimicking ST-segment elevation myocardial infarction, which was successfully treated by emergent laparotomy.

Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue.

The use of animal organs could potentially alleviate the critical worldwide shortage of donor organs for clinical transplantation. Because of the strong immune response to xenografts, success will probably depend upon new strategies of immune suppression and induction of tolerance. Here we report our initial results using alpha-1,3-galactosyltransferase knockout (GalT-KO) donors and a tolerance induction approach. We have achieved life-supporting pig-to-baboon renal xenograft survivals of up to 83 d with normal creatinine levels.

Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience.

Hearts from alpha1,3-galactosyltransferase knockout pigs (GalT-KO, n = 8) were transplanted heterotopically into baboons using an anti-CD154 monoclonal antibody-based regimen. The elimination of the galactose-alpha1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2-6 months (median, 78 d); the predominant lesion associated with graft failure was a thrombotic microangiopathy, with resulting ischemic injury. There were no infectious complications directly related to the immunosuppressive regimen. The transplantation of hearts from GalT-KO pigs increased graft survival over previous studies.

Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons.

Heterotopic cardiac xenotransplantation from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) swine to baboons was performed to characterize immunological reaction to the xenograft in the absence of anti-Gal antibody-mediated rejection. Eight baboons received heterotopic cardiac xenografts from GalT-KO porcine donors. All baboons were treated with chronic immunosuppressive therapy. Both histological and immunohistochemical studies were performed on biopsy and graftectomy samples. No hyperacute rejection was observed. Three baboons were euthanized or died 16 to 56 days after transplantation. The other five grafts ceased beating between days 59 and 179 (median, 78 days). All failing grafts exhibited thrombotic microangiopathy (TM) with platelet-rich fibrin thrombi in the microvasculature, myocardial ischemia and necrosis, and focal interstitial hemorrhage. TM developed in parallel with increases in immunoglobulin (IgM and IgG) and complement (C3, C4d, and C5b-9) deposition, as well as with subsequent increases in both TUNEL(+) endothelial cell death and procoagulant activation (increased expression of both tissue factor and von Willebrand factor and decreased expression of CD39). CD3(+) T-cell infiltration occurred in all grafts and weakly correlated with the development of TM. In conclusion, although the use of GalT-KO swine donors prevented hyperacute rejection and prolonged graft survival, slowly progressive humoral rejection--probably associated with non-Gal antibodies to the xenograft--and disordered thromboregulation represent major immunological barriers to long-term xenograft survival.

Long-term acceptance of fully allogeneic cardiac grafts by cotransplantation of vascularized thymus in miniature swine.

BACKGROUND: We have previously reported the ability of both thymokidney and vascularized thymic lobe (VTL) allografts to induce transplantation tolerance to renal allografts across a full major histocompatibility complex (MHC) mismatch in thymectomized miniature swine. However, whether vascularized thymus is capable of inducing tolerance to less tolerogeneic organs when it is transplanted simultaneously is not yet known. The present study investigates cardiac allograft survival and the mechanism of long-term acceptance in recipient swine following cotransplantation of VTL and cardiac grafts from fully MHC-mismatched donors. METHODS: Animals received a heart graft, a heart graft and a VTL, or a heart graft and a donor thymocyte infusion. Immunosuppressive regimens consisted of 12 or 28 days of tacrolimus. RESULTS: All animals that received a VTL maintained their grafts significantly longer than their counterparts that received only a heart graft, and those receiving 28 days of tacrolimus maintained their heart grafts long-term. Recipients of a donor thymocyte infusion demonstrated slightly prolonged cardiac graft survival but all rejected their grafts, highlighting the importance of thymic stroma. Cytotoxic T-lymphocyte responses against third-party antigens by cells from tolerant animals showed restriction by both self and donor MHC, whereas responses of controls were restricted to self MHC only. The presence of donor dendritic cells in the VTL grafts and results of co-culture assays suggest that both central and regulatory mechanisms were involved in achieving long-term acceptance. CONCLUSION: This is the first demonstration of the long-term acceptance of fully MHC-mismatched cardiac allografts in large animals.

alpha1,3-Galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months.

BACKGROUND: The recent generation of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs has allowed investigation of the survival of GalT-KO pig organs in nonhuman primates. METHODS: Heterotopic heart transplantation from GalT-KO pigs was carried out in baboons (n=8) using a human antihuman CD154 monoclonal antibody-based immunosuppressive regimen. RESULTS: In six of the eight cases, graft survival extended to between approximately 2 and 6 months. All grafts developed thrombotic microangiopathy (TM). In particular, the clinical course of one baboon in which the graft functioned for 179 days is summarized. This baboon received aspirin (40 mg on alternate days) from day 4 in addition to heparin, which may have been a factor in the delay of onset and progression of TM and in prolonged graft survival. Maintenance therapy with anti-CD154 mAb, mycophenolate mofetil, and methylprednisolone was associated with persistently low numbers of CD3CD4 and CD3CD8 cells. Despite persisting depletion of these cells, no infectious complications occurred. CONCLUSIONS: It remains to be established whether TM is related to a very low level of natural preformed or T-cell-induced antibody deposition on the graft, inducing endothelial activation and injury, or to molecular incompatibilities in the coagulation mechanisms between pig and baboon, or to both. However, function of a pig organ in a baboon for a period approaching six months, which has not been reported previously, lends encouragement that the barriers to xenotransplantation will eventually be overcome.

Replacement of the heavily calcified ascending aorta in aortic valve replacement.

A totally calcified ascending aorta prevents aortic crossclamping and aortotomy during aortic valve replacement, and replacement of the ascending aorta is a valid option in these cases. We describe a simple technique for calcified ascending aorta replacement using the Cavitron Ultrasonic Surgical Aspirator. This can be used in aortic endarterectomy for removal of the calcified plaque in the anastomotic part.

A rare cardiac haemangioma in the right ventricle diagnosed accurately using ¹8F-fluorodeoxyglucose-positron emission tomography.

A right ventricular cardiac tumour was incidentally detected in a 61-year-old man during a preoperative examination for coronary artery bypass grafting (CABG). Findings on computed tomography and magnetic resonance imaging suggested the differential diagnoses of myxoma, haemangioma and haemangiosarcoma, and it was difficult to identify whether the tumour was benign or malignant. (18)F-fluorodeoxyglucose-positron emission tomography strongly suggested a benign tumour. We enucleated the tumour, because an intraoperative frozen section also strongly suggested a benign origin. After resection, CABG under cardiopulmonary bypass was performed. Histopathological and immunohistochemical analysis indicated a cavernous haemangioma without evidence of malignant tissue. The patient has survived 20 months after surgery with no evidence of tumour recurrence.

Bone marrow is a source of regenerated cardiomyocytes in doxorubicin-induced cardiomyopathy and granulocyte colony-stimulating factor enhances migration of bone marrow cells and attenuates cardiotoxicity of doxorubicin under electron microscopy.

BACKGROUND: It has been reported previously that granulocyte colony-stimulating factor (GCSF) injection improves infarcted heart function, but the mechanism remains unclear. In this study we sought to determine whether GCSF-mobilized bone marrow cells could regenerate neo-myocardium and repair doxorubicin-induced cardiomyopathy. METHODS: C57BL/6 mice were irradiated and bone marrow cells (BMC; 1 x 10(6)) from green fluorescent protein (GFP) mice (GFP-BMC) were transplanted intravenously, followed by splenectomy. Doxorubicin (2.5 mg/kg, 6 times for 2 weeks) was administered intraperitoneally 2 weeks later. GCSF (50 microg/kg/day for 8 days) was administered sub-cutaneously after doxorubicin injection (Group I, n = 11) and 3 weeks later (Group II, n = 8), and saline was injected in Group III animals (n = 8). Eight weeks after doxorubicin injection, the excised hearts were studied immunologically and electron microscopically. RESULTS: Survival rates were 81.8% in Group I, 50.0% in Group II and 62.5% in Group III. The number of GFP-BMC in Group I (15.4 +/- 7.4 per high-power field) was highest (p < 0.05). In all groups, cardiac troponin I-positive cells derived from GFP-BMC were observed in the hearts. GFP-BMC in hearts stained positively against cardiac troponin I (4.3 +/- 2.5%), myosin heavy chain (5.0 +/- 4.3%), atrial natriuretic peptide (ANP; 3.9 +/- 2.4%) and connexin 43 (11.9 +/- 7.3%) in Group I. Myofibrils, mitochondria and fundamental architecture were almost all preserved in Group I, whereas hearts were severely damaged in Groups II and III. CONCLUSIONS: Bone marrow was shown to be one of the sources of regenerated cardiomyocytes in the doxorubicin-induced cardiomyopathic heart. Early administration of GCSF enhanced the migration of bone marrow cells into the heart, and attenuated the cardiotoxicity of doxorubicin.

Granulocyte-colony stimulating factor enhanced the recruitment of bone marrow cells into the heart: time course evaluation of phenotypic differentiation in the doxorubicin-induced cardiomyopathic model.

OBJECTIVE: We traced and evaluated bone marrow-derived cells after granulocyte-colony stimulating factor (G-CSF) treatment in the doxorubicin-induced cardiomyopathic heart in the time course. METHODS: C57BL/6 male mice received doxorubicin (15 mg/kg, i.p.). At 1 week after administration of doxorubicin, the mice were irradiated (900 cGy) followed by transplantation of bone marrow cells (BMT) derived from transgenic mice expressing green fluorescent protein (GFP) (1 x 10(6)) via a tail vein (BMT). G-group (n = 22) received G-CSF (50 microg/kg/day x 8 days, s.c.) after BMT, while C-group (n = 17) received saline. At 4 and 7 weeks after BMT, heart sections were fixed to evaluate bone marrow-derived GFP cells (BMD-GFP) with immunostaining for Troponin I (TnI), atrial-natriuretic peptide (ANP), connexin 43, von Willebrand factor, and Ki67. RESULT: There were migrated BMD-GFP in the whole heart of all animals. In the time course, migrated BMD-GFP increased in G-group. At 7 weeks the number of migrated BMD-GFP in G-group (56.2 +/- 15.6/HPF) was larger than that in C-group (18.9 +/- 10.7/HPF) (p < 0.05). TnI- and connexin 43-positive BMD-GFP were spindle-shaped. Von Willebrand factor-positive BMD-GFP showed thinner-shape. ANP- and Ki67-positive BMD-GFP showed oval-shape. The numbers of these positive cells derived from BMD-GFP, not different between the 2 groups, did not change from 4 to 7 weeks. CONCLUSION: The migration of BMD-GFP into the heart increased from 4 to 7 weeks after BMT by G-CSF. However, cardiomyocytes and endothelial cells originating from BMD-GFP were very few and neither increased nor changed in their shapes and numbers in the short term.

Tricuspid regurgitation after mitral valve repair for degenerative mitral regurgitation.

PURPOSE: We examined changes of TR (tricuspid regurgitation) after mitral valve repair for degenerative mitral regurgitation (MR) and investigated their contributing parameters. METHODS: We divided 205 patients undergoing mitral valve repair for degenerative MR into 3 groups: up-grade (n = 65), down-grade (n = 29), and no-change (n = 111) of TR during postoperative follow-up. Preoperative, immediate postoperative, and mid-term postoperative parameters included MR grade, right ventricular (RV) pressure, RV Tei index, left ventricular Tei index, and presence of atrial fibrillation. RESULTS: Preoperative incidence of atrial fibrillation in the down-grade group was lower (7%) than those in the other groups (37% and 34%). In the immediate postoperative stage, the TR grade of the up-grade group was significantly lower (p <0.001) and RV Tei index of the downgrade group was significantly lower (p = 0.049). In mid-term postoperative stage, the TR grade (p <0.001) and RV Tei index (p = 0.034) of the down-grade group were significantly lower, and the MR up-grade in the TR up-grade group was significantly frequent (p = 0.008). CONCLUSIONS: TR became deteriorated even after the operation in about 30% and remained unchanged in about 50%. The RV Tei index can be a reliable parameter to predict postoperative improvement of TR. The postoperative MR up-grade was related to the TR up-grade.

Should mitral annuloplasty be performed for patients with mild ischemic mitral regurgitation?

PURPOSE: We investigated whether mitral annuloplasty (MAP) should be performed for mild ischemic mitral regurgitation (IMR). METHODS: We selected 57 patients with preoperatively mild IMR. Twenty-eight patients who previously had moderate MR or more, underwent MAP (group 1) while 29 patients with persistent mild MR, did not (group 2). We reviewed MR changes and outcomes of these patients. We also investigated other IMR patients with preoperatively moderate or more MR as reference data (group 3). RESULTS: In group 1, MR was none or trace in 25 patients immediately after operation, however, eleven out of these patients (44%) showed postoperative MR up-grade. The trends of MR changes in group 1 were similar to those of patients in group 3. In group 2, MR was graded mild in 79% of patients in mid-term postoperative stage although 28% of patients were up-graded or down-graded during postoperative follow-up. CONCLUSION: MAP is not necessary for patients with persistently mild IMR. Patients with preoperatively mild IMR with episodes of MR exacerbation had better be treated similarly as those with moderate or more IMR and undergo MAP.

Impact of diabetes mellitus on outcomes in Japanese patients undergoing coronary artery bypass grafting.

BACKGROUND AND PURPOSE: There have been no large-scale studies on the impact of diabetes mellitus (DM) on outcomes in Japanese patients undergoing coronary artery bypass grafting (CABG). METHODS AND SUBJECTS: A multi-institutional retrospective cohort study was conducted in 14 Japanese centers. All adult patients who underwent isolated CABG from 2007 to 2008 were included (n=1522, mean age: 68.5years). The definitions of DM were all patients admitted with diagnosis of DM and preoperative glycated hemoglobin (Hb) A1c≥6.5%. Univariate and multivariate analyses were performed to identify the risk of morbidity and mortality. RESULTS: There were 849 DM and 572 non-DM patients. Preoperative mean HbA1c were 7.1% in the DM group and 5.7% in the non-DM group (p<0.0001). Preoperative, intraoperative, and 3-day average postoperative blood glucose (BG) were 146mg/dl, 172mg/dl, and 168mg/dl in the DM group, and 103mg/dl, 140mg/dl, and 136mg/dl in the non-DM group (all p<0.0001). Although there were no significant differences in postoperative cardiovascular events, the incidence of infection was significantly higher in the DM group than in the non-DM group (9.2% vs 6.1%, p=0.036) on the univariate analysis. The all-cause death was also relatively higher in the DM group than in the non-DM group (2.1% vs 1.1%, p=0.12), and this was likely related to infection. CONCLUSION: DM patients had worse perioperative BG control, higher incidence of infection, and higher mortality than non-DM patients. These results indicate that perioperative BG control guidelines should be standardized to obtain better surgical outcomes in Japanese DM patients.

Left ventricular reconstruction with or without mitral annuloplasty.

OBJECTIVES: The aim of this study was to review characteristics of patients undergoing left ventricular reconstruction (LVR) with or without mitral annuloplasty (MAP) for postinfarction ventricular remodeling. PATIENTS AND METHODS: Forty-seven patients were divided into two groups: LVR (LVR group, n = 22) and LVR with MAP (LVRM group, n = 25). Echocardiographic parameters including left ventricular (LV) dimensions, LV end-diastolic and end-systolic volume indexes, and LV ejection fraction (LVEF) at immediate and midterm postoperative stages were evaluated. The perioperative contributing factors to all deaths and death from congestive heart failure (CHF) were analyzed in all 47 patients. RESULTS: Patients in the LVRM group had greater preoperative LV dimension and volume, and significantly lower LVEF, with notably frequent use of intra-aortic balloon pumping. All postoperative deaths occurred within 1 year from surgery. The LV end-diastolic volume > 110 ml/m2 and creatinine > 1.2 mg/dl were significant preoperative contributing factors to all deaths, and the latter was to CHF deaths. CONCLUSIONS: The coexistence of ischemic mitral regurgitation with LV dilatation required more aggressive surgical approaches for the patients with more impaired LV function. More intensive postoperative management is required for patients with enlarged hearts and renal dysfunctions.