岡村 誉

Right-sided aortic arch (RAA) is a rare congenital disorder. We describe herein two cases of thoracic aortic aneurysm with a right aortic arch and right-sided descending aorta treated with thoracic endovascular aortic repair (TEVAR). In one case, a 70-year-old man with Edwards type 1 RAA underwent TEVAR using a Relay stent-graft (Bolton Medical, Barcelona, Spain). In another case, a 72-year-old woman with Edwards type 3 RAA underwent TEVAR using a Kawasumi Najuta stent-graft (Kawasumi Laboratories, Inc., Tokyo, Japan) with the "buffalo horn chimney technique", our original method for left subclavian artery flow preservation. The postoperative courses were uneventful. Postoperative computed tomography showed complete exclusion of the aneurysm without endoleakage. Compared to conventional open surgical repair, TEVAR is challenging in patients with a RAA and right-sided descending aorta. However, our results showed that TEVAR might be feasible and a treatment option even in a patient with a RAA and right-sided descending aorta.

OBJECTIVES: Use of the left internal mammary artery in patients with diabetes mellitus and multivessel coronary artery disease is known to improve survival after coronary artery bypass grafting (CABG); however, the survival benefit of multiple arterial grafts (MAGs) in diabetic patients is debated. We investigated the efficacy of CABG performed with MAGs in diabetic patients. METHODS: The overall patient group comprised 2618 consecutive patients who underwent isolated CABG at our hospital between 1990 and 2014. Perioperative characteristics, in-hospital outcomes and long-term outcomes were compared between diabetic (n = 1110) and non-diabetic patients (n = 1508). The long-term outcomes of diabetic and non-diabetic patients were analysed between those who received a single arterial graft (SAG) and those who received MAGs. Both full unmatched patient population and propensity-matched patient population analyses (diabetic cohort = 431 pairs, non-diabetic cohort = 577 pairs) were performed. RESULTS: Preoperative comorbidities were much more common in the diabetic patients than in the non-diabetic patients; however, comorbidities were not associated with in-hospital outcomes (diabetes versus non-diabetes group, in-hospital mortality: 2.2 vs 1.5%; deep sternal wound infection: 2.2 vs 1.8%, P > 0.05). Although survival and freedom from major cardiac and cerebrovascular events (MACCEs) at 15 years were lower in the diabetes group than in the non-diabetes group (survival: 48.6 vs 55.0%, P = 0.019; MACCE-free survival: 40.8 vs 46.1%, P = 0.02), cardiac death-free survival at 15 years was similar (81.7 vs 83.9%, P = 0.24). Overall, 12-year survival was higher in both diabetic and non-diabetic patients treated with MAGs than in those treated with an SAG (64.9 vs 56.8%, P = 0.006, and 71.9 vs 60.5%, P < 0.001). Propensity-matched patient cohort analysis revealed improved 12-year survival with MAGs versus SAG in both the diabetes group (64.9 vs 58.8%, P = 0.041) and non-diabetes group (71.4 vs 63.8%, P = 0.014). Similarly, MACCE-free survival was improved in both groups. CONCLUSIONS: A long-term survival advantage, with no increase in perioperative morbidity, is conferred with the use of multiple arterial bypass grafts not only in non-diabetic patients but also in diabetic patients.

Standard full median sternotomy for total aortic arch replacement in patients with tracheostomy has higher risks for mediastinitis and graft infection. To avoid surgical site infection, it is necessary to keep a sufficient distance between the tracheostomy and the site of surgical skin incision. We herein report a case of a 74-year-old man with permanent tracheostomy after total laryngectomy, who underwent total aortic arch replacement for an aneurysm. Antero-lateral thoracotomy in the 2nd intercostal space with lower partial sternotomy( ALPS approach) provided an enough distance between the tracheostomy and the surgical field. It also provided a good view for surgical procedure and enabled the standard setup of cardiopulmonary bypass with ascending aortic cannulation, venous drainage from the right atrium and the left ventricular venting through the upper right pulmonary vein. The operation was completed in 345 minutes and the patient was discharged on the 11th postoperative day without any complications.

OBJECTIVE: Rupture and dissection of aortic root aneurysms remain the leading causes of death in patients with the Marfan syndrome, a hereditary connective tissue disorder that affects 1 in 5000 individuals worldwide. In the present study, we use a Marfan mouse model (Fbn1(C1039G/+)) to investigate the biological importance of apoptosis during aneurysm development in Marfan syndrome. APPROACH AND RESULTS: Using in vivo single-photon emission computed tomographic-imaging and ex vivo autoradiography for Tc99m-annexin, we discovered increased apoptosis in the Fbn1(C1039G/+) ascending aorta during early aneurysm development peaking at 4 weeks. Immunofluorescence colocalization studies identified smooth muscle cells (SMCs) as the apoptotic cell population. As biological proof of concept that early aortic wall apoptosis plays a role in aneurysm development in Marfan syndrome, Fbn1(C1039G/+) mice were treated daily from 2 to 6 weeks with either (1) a pan-caspase inhibitor, Q-VD-OPh (20 mg/kg), or (2) vehicle control intraperitoneally. Q-VD-OPh treatment led to a significant reduction in aneurysm size and decreased extracellular matrix degradation in the aortic wall compared with control mice. In vitro studies using Fbn1(C1039G/+) ascending SMCs showed that apoptotic SMCs have increased elastolytic potential compared with viable cells, mostly because of caspase activity. Moreover, in vitro (1) cell membrane isolation, (2) immunofluorescence staining, and (3) scanning electron microscopy studies illustrate that caspases are expressed on the exterior cell surface of apoptotic SMCs. CONCLUSIONS: Caspase inhibition attenuates aneurysm development in an Fbn1(C1039G/+) Marfan mouse model. Mechanistically, during apoptosis, caspases are expressed on the cell surface of SMCs and likely contribute to elastin degradation and aneurysm development in Marfan syndrome.

BACKGROUND: Ascending aortic dissection and rupture remain a life-threatening complication in patients with Marfan syndrome. The extracellular matrix provides strength and elastic recoil to the aortic wall, thereby preventing radial expansion. We have previously shown that ascending aortic aneurysm formation in Marfan mice (Fbn1(C1039G/+)) is associated with decreased aortic wall elastogenesis and increased elastin breakdown. In this study, we test the feasibility of quantifying aortic wall elastin content using MRI with a gadolinium-based elastin-specific magnetic resonance contrast agent in Fbn1(C1039G/+) mice. METHODS AND RESULTS: Ascending aorta elastin content was measured in 32-week-old Fbn1(C1039G/+) mice and wild-type (n=9 and n=10, respectively) using 7-T MRI with a T1 mapping sequence. Significantly lower enhancement (ie, lower R1 values, where R1=1/T1) was detected post-elastin-specific magnetic resonance contrast agent in Fbn1(C1039G/+) compared with wild-type ascending aortas (1.15±0.07 versus 1.36±0.05; P<0.05). Post-elastin-specific magnetic resonance contrast agent R1 values correlated with ascending aortic wall gadolinium content directly measured by inductively coupled mass spectroscopy (P=0.006). CONCLUSIONS: Herein, we demonstrate that MRI with elastin-specific magnetic resonance contrast agent accurately measures elastin bound gadolinium within the aortic wall and detects a decrease in aortic wall elastin in Marfan mice compared with wild-type controls. This approach has translational potential for noninvasively assessing aneurysm tissue changes and risk, as well as monitoring elastin content in response to therapeutic interventions.

OBJECTIVE: Since drug-eluting stents (DESs) appeared in Japan, coronary artery bypass grafting (CABG) has been indicated for more severe lesions. To understand the implications of this trend, we compared SYNTAX scores in two groups of patients treated with CABG before and after DESs approval. METHODS: Consecutive CABG patients during January 2001-July 2003 (pre-DES era patients, n = 160) and January 2008-July 2010 (DES era patients, n = 103) were included. The SYNTAX scores of both groups were compared and a cardiologist retrospectively re-evaluated coronary angiograms to determine whether CABG or percutaneous coronary intervention (PCI) would be recommended under current standards. RESULTS: SYNTAX scores were significantly higher in DES era group compared with pre-DES era group (33.3 ± 10.6 vs. 28.1 ± 10.6, p < 0.01). Percutaneous coronary intervention would be the preferred treatment option in 66 (41 %) of pre-DES patients, whose SYNTAX scores were significantly lower than those of patients who were considered good candidates for CABG (21.9 ± 9.3 vs. 32.5 ± 9.1, p < 0.01). CONCLUSIONS: Although CABG is now being performed in intermediate-to-highly complex cases, DES era outcomes, including operative mortality and early graft failure, have not worsened in comparison to the pre-DES era.

The shortage of donors has limited the number of heart transplantations. We report a successful ex vivo mitral valve repair of the allograft prior to heart transplantation.

PURPOSE: The effective orifice area index (EOAI) is used to define the prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR). However, few studies have so far evaluated whether the cutoff value for PPM varies across prostheses. This study assessed the hemodynamics in patients given a mechanical valve and then re-evaluated the validity of the commonly accepted threshold. METHODS: The subjects included 329 patients that underwent AVR with a St. Jude Medical Regent valve. The transvalvular pressure gradient and EOAI were determined echocardiographically, and the commonly accepted threshold was analyzed in relation to survival. RESULTS: The mechanical valves very often yielded a postoperative transvalvular pressure gradient >10 mmHg, and thus, clinically significant residual pressure, regardless of the EOAI. The slope of the curve describing the relationship between the transvalvular pressure gradient and EOAI was gentler than that reported for bioprosthetic valves, for which the pressure gradient rises sharply at EOAI <0.85 cm(2)/m(2). The commonly defined PPM did not affect the long-term survival or regression of the left ventricular mass index. CONCLUSIONS: The relationship between the transvalvular pressure gradient and the EOAI in patients given a mechanical prosthesis differed from the reference standard. These data suggest the need to reconsider the appropriate cutoff value for PPM in relation to different prostheses.

Despite advanced immunosuppression, redundancy in the molecular diversity of acute rejection (AR) often results in incomplete resolution of the injury response. We present a bioinformatics based approach for identification of these redundant molecular pathways in AR and a drug repositioning approach to suppress these using FDA approved drugs currently available for non-transplant indications. Two independent microarray data-sets from human renal allograft biopsies (n = 101) from patients on majorly Th1/IFN-y immune response targeted immunosuppression, with and without AR, were profiled. Using gene-set analysis across 3305 biological pathways, significant enrichment was found for the IL17 pathway in AR in both data-sets. Recent evidence suggests IL17 pathway as an important escape mechanism when Th1/IFN-y mediated responses are suppressed. As current immunosuppressions do not specifically target the IL17 axis, 7200 molecular compounds were interrogated for FDA approved drugs with specific inhibition of this axis. A combined IL17/IFN-y suppressive role was predicted for the antilipidemic drug Fenofibrate. To assess the immunregulatory action of Fenofibrate, we conducted in-vitro treatment of anti-CD3/CD28 stimulated human peripheral blood cells (PBMC), and, as predicted, Fenofibrate reduced IL17 and IFN-γ gene expression in stimulated PMBC. In-vivo Fenofibrate treatment of an experimental rodent model of cardiac AR reduced infiltration of total leukocytes, reduced expression of IL17/IFN-y and their pathway related genes in allografts and recipients' spleens, and extended graft survival by 21 days (p<0.007). In conclusion, this study provides important proof of concept that meta-analyses of genomic data and drug databases can provide new insights into the redundancy of the rejection response and presents an economic methodology to reposition FDA approved drugs in organ transplantation.

BACKGROUND: Although αβ T cells are known to participate in the development of acute cardiac allograft rejection, the role of γδ T cells remains poorly understood. We hypothesized that γδ T cells contribute to acute allograft rejection thru interleukin (IL)-17 production. METHODS: Donor hearts from FVB mice (H-2q) were heterotopically transplanted into C57BL/6-wild type (WT) and γδ T cell-deficient (TCRδ-/-) recipient mice (H-2b). Overall graft survival was monitored. Graft infiltrating cell profile, including γδ T cell subtype, cytokine expression, and myeloperoxidase activity were measured by flow cytometry, TaqMan (Applied Biosystems, Carlsbad, CA) polymerase chain reaction, and myeloperoxidase assay, respectively, on postoperative days 3 and 6. RESULTS: Graft survival was prolonged in TCRδ-/- recipients compared with WT controls. Graft infiltrating cells, including CD45+, CD4+, CD8+, and Gr1+ cells were significantly decreased in TCRδ-/- recipients compared with WT. Donor hearts transplanted into TCRδ-/- recipients had reduced IL-17 and IL-6 messenger RNA expression. Corroborating the gene expression, intracellular cytokine staining showed decreased IL-17 producing cells in TCRδ-/- recipients. Finally, Vγ1+ and Vγ4+ T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating γδ T cells. CONCLUSIONS: The γδ T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The γδ T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production.

BACKGROUND: When aortic valve replacement is performed in patients with a small aortic annulus, prosthesis-patient mismatch (PPM) is of concern because it can affect postoperative clinical outcomes. Although larger bioprosthetic valves have been well studied, the hemodynamics of 19-mm bioprostheses have been reported in only a small number of patients. The effectiveness as well as the impact of PPM on outcomes are thus still unclear. METHODS AND RESULTS: Postoperative clinical and hemodynamic variables were compared in 67 patients with a 19-mm Carpentier Edwards Perimount Magna bioprosthesis and in 10 patients with a 19-mm Medtronic Mosaic Ultra valve. Mean follow-up time was 13 months. There was no in-hospital mortality. Echocardiography 6.5±4.0 months after surgery showed significant decreases in the mean left ventricular (LV)-aortic pressure gradient, and decreases in the mean LV mass index. Reduction in LV mass index did not differ between the valve groups, despite a higher pressure gradient in the Mosaic group. Although PPM was detected in 21 patients in the Magna group, it did not affect regression of the LV mass index during the follow-up period. CONCLUSIONS: Use of the 19-mm Magna bioprosthesis appears to provide satisfactory clinical results. LV-aortic pressure gradient was lower in the Magna group. The present data suggest that PPM is not related to reduction in the LV mass index.

BACKGROUND: When aortic valve replacement (AVR) is performed in patients with a small aortic annulus, prosthesis-patient mismatch (PPM) is of concern. We investigated the mid-term outcomes of AVR with a 17-mm mechanical prosthesis. METHODS AND RESULTS: Seventy-eight patients with aortic stenosis underwent AVR with a 17-mm St. Jude Medical Regent prosthesis. Echocardiography was performed preoperatively, at discharge, and at follow-up (mean follow-up, 33 months). Patients were divided into 2 groups: with and without PPM at discharge. Between-group differences in postoperative variables, particularly survival, were analyzed. Overall hospital mortality was 2.6%. Actuarial 1- and 5-year survival rates were 95% and 79%, respectively. Diabetes and renal insufficiency were associated with long-term mortality. Freedom from major adverse valve-related cardiac events at 1 year and 5 years was 97.3% and 93.9%, respectively. Diabetes was shown to be an independent risk factor for major adverse valve-related cardiac events. Echocardiography 13 months after AVR showed a significant increase in mean effective orifice area index, decrease in mean left ventricular-aortic pressure gradient, and decrease in mean left ventricular mass index. PPM at discharge did not influence long-term survival or left ventricular mass regression. CONCLUSIONS: The 17-mm Regent prosthesis provided satisfactory clinical and hemodynamic results. It is a reliable choice for patients with a small aortic annulus.

BACKGROUND: IL-16 promotes the recruitment of various cells expressing CD4, a receptor for IL-16. The precise role of IL-16 in transplant rejection remains unknown; therefore, the present study investigated the contribution of IL-16 to the development of chronic rejection in heart transplants. METHODS: C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into (1) IL-16-deficient (IL-16(-/-)) C57BL/6J or (b) wild type (WT) control recipients (MHC class II mismatch). Grafts were harvested at 52 days, parenchymal rejection was assessed by the ISHLT grading system, and CAV was examined morphometrically. Graft infiltrating cells were detected 10 and 52 days after transplantation. Intragraft cytokine and chemokine profiles were assessed. To confirm the role of IL-16 in CAV development, C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into C57BL/6J WT recipients treated with (1) anti-IL-16-neutralization monoclonal antibody or (b) control immunoglobulin G. Grafts were harvested at 52 days, and CAV was quantified morphometrically. Graft-infiltrating cells were examined histologically. RESULTS: Parenchymal rejection and CAV was significantly attenuated in donor hearts transplanted into IL-16(-/-) recipient mice compared with WT controls. Donor hearts transplanted into IL-16(-/-) recipients had a significant reduction in coronary artery luminal occlusion, intima-to-media ratio, and percentage of diseased vessels. CAV was associated with decreased donor organ inflammation, as well as donor organ cytokine (IL-1β and IL-6) and chemokine (MCP-1 and KC) protein expression. Intimal proliferation and inflammatory cell infiltration were significantly reduced in hearts transplanted into recipients treated with an IL-16-neutralization antibody. CONCLUSIONS: IL-16-deficiency reduced graft inflammatory cell recruitment, and allograft inflammatory cytokine and chemokine production. Therefore, IL-16 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.

Intravenous leiomyomatosis with cardiac extension is rare and may result in a fatal outcome. A 58-year-old woman with a surgical history of myoma uteri was admitted to our hospital for treatment of intravenous leiomyomatosis extending into the right atrium through the inferior vena cava. We partially resected the tumor inside the right atrium and the inferior vena cava via the right atrium using cardiopulmonary bypass. There is no progression of the residual tumor after 25 months of follow-up.

BACKGROUND: Acute type A aortic dissection (AAAD) is rare in young people. The early- and long-term outcomes after surgery for AAAD in patients aged ≤ 45 years was investigated. METHODS AND RESULTS: Subjects were 355 patients who had undergone emergency surgery for AAAD. The patients were grouped as those aged ≤ 45 years (n=30; mean age, 38.3 years; younger group) and those aged > 45 years (n = 325; mean age, 65.3 years; older group). Clinical and prognostic variables were compared between the groups. Male sex, Marfan syndrome, and severe aortic regurgitation were more prevalent in the younger group. In-hospital mortality (16.7% vs. 8.6%, P = 0.15) and postoperative patency of the distal aorta (90.8% vs. 59.1%, P < 0.01) were more frequent in the younger group. The leading causes of late death were aortic rupture in the younger group (75.0%) and malignancy in the older group (27.5%). Although actuarial survival at 10 years was similar (64.5% vs. 62.5%), freedom from aortic reoperation at 10 years was decreased in the younger group (49.4% vs. 85.0%, P = 0.012). A distal aorta > 45 mm (P<0.001), Marfan syndrome (P < 0.01), and age ≤ 45 years (P = 0.045) were shown to be independent risk factors for reoperation. CONCLUSIONS: Early- and long-term surgical outcomes are not better for patients ≤ 45 years, and the risk for reoperation is high in this group. Careful follow up is important in young patients with AAAD.

Cardiac surgery in patients with a positional anomaly of the heart is technically challenging, and very few reports exist of such surgery in patients with dextrocardia. A 73-year-old woman in whom dextrocardia with situs solitus had been diagnosed at a young age, presented with palpitation and shortness of breath due to significant mitral valve insufficiency. Cardiopulmonary bypass (CPB) was initiated through aortic, superior vena cava, and inferior vena cava cannulae. The use of a heart positioner simplified and made safe the initiation of CPB. A left-sided left atriotomy provided excellent exposure of the mitral valve, and mitral valve replacement (MVR) was safely performed with a 25 mm St. Jude Medical mechanical prosthesis. The postoperative course was uneventful. In patients with dextrocardia requiring cardiac surgery, it is important to consider the appropriate surgical strategy. Approaching the mitral valve through a left-sided left atrial incision seems to provide excellent exposure for MVR.

When aortic valve replacement is performed in patients with a small aortic annulus, prosthesis-patient mismatch is of concern because it may affect postoperative clinical status. We conducted a retrospective study of outcomes in 65 patients with aortic stenosis requiring valve replacement. Fifty were given a 17-mm or 19-mm St. Jude Regent mechanical valve, and 15 were given a 19-mm Medtronic Mosaic bioprosthesis. Echocardiography was carried out preoperatively, at discharge, and at follow-up. There was 1 (2%) operative death in the Regent group and none in the Mosaic group. There was no valve-related event. Follow-up echocardiography in both groups revealed a significant increase in the mean effective orifice area index, a decrease in the mean left ventricular-aortic pressure gradient, and a decrease in the mean left ventricular mass index. Prosthesis-patient mismatch (effective orifice area index <0.85 cm(2) · m(-2)) existed in 13 (26%) patients in the Regent group and 11 (73%) in the Mosaic group at discharge. All patients improved to New York Heart Association functional class II or better. A small-sized prosthesis may provide satisfactory clinical and hemodynamic results in patients with a small aortic annulus.

PURPOSE: The aim of this study was to clarify the efficacy of intravenous milrinone in postoperative care for patients following left ventricular (LV) restoration (LVR). METHODS: Fourteen patients who had ischemic cardiomyopathy with an LV ejection fraction (LVEF) of less than 0.30 and an LV end-systolic volume index of more than 100 ml/m2 underwent coronary artery bypass grafting and concomitant LVR. The patients received perioperative management with continuous infusions of 0.5 microg/kg/min milrinone that were started at the induction of a cardiopulmonary bypass (CPB). The perioperative course and outcome of these patients were retrospectively compared with those of matched LVR patients (n = 14) without milrinone administration during perioperative management. RESULTS: The preoperative LV end-diastolic pressure (26.3 mmHg vs. 15.4 mmHg) and early diastolic filling velocity/atrial filling velocity ratio (4.1 vs. 2.1) in the milrinone patients were significantly worse than those in the control. Even though the preoperative LV function in each patient demonstrated to be extremely poor, the perioperative hemodynamic variables were stable. The administered doses of dobutamine (4.01 vs. 5.81 microg/kg/min) and epinephrine (0.017 vs. 0.038 microg/kg/min) at the end of CPB were significantly lower in the milrinone patients compared to control. CONCLUSION: In those patients who underwent LVR because of ischemic cardiomyopathy, the administration of milrinone achieved safe perioperative management for stable hemodynamics and reduced the postoperative doses of dobutamine and epinephrine.

BACKGROUND: When aortic valve replacement is performed in patients with a small aortic annulus, prosthesis-patient mismatch is of concern. Such prosthesis-patient mismatch may affect postoperative clinical status and survival. We investigated the outcomes of isolated aortic valve replacement performed with a 17-mm mechanical prosthesis in patients with aortic stenosis. METHODS: Twenty-three patients with aortic stenosis (mean age, 74.6 +/- 6.3 years) underwent isolated aortic valve replacement with a 17-mm St. Jude Medical Regent prosthesis. Mean body surface area was 1.41 +/- 0.13 m(2). Preoperative echocardiography yielded a mean aortic valve area of 0.36 +/- 0.10 cm(2)/m(2), a mean left ventricular-aortic pressure gradient of 68.4 +/- 25.3 mm Hg, and a mean left ventricular mass index of 200 +/- 69 g/m(2). RESULTS: There was no operative mortality, and there were no valve-related events. Echocardiography at 14.0 +/- 10.0 months after aortic valve replacement showed a significant increase in the mean effective orifice area index (0.95 +/- 0.24 cm(2)/m(2)), decrease in the mean left ventricular-aortic pressure gradient (17.4 +/- 8.2 mm Hg), and decrease in the mean left ventricular mass index (124 +/- 37 cm(2)/m(2)). Prosthesis-patient mismatch (effective orifice area index < 0.85 cm(2)/m(2)) was present in 8 patients at discharge. In these patients as well as in those without prosthesis-patient mismatch, the left ventricular mass index decreased remarkably during follow-up. CONCLUSIONS: Aortic valve replacement with a 17-mm Regent prosthesis appears to provide satisfactory clinical and hemodynamic results in patients with a small aortic annulus. Remarkable left ventricular mass regression during follow-up was achieved irrespective of the effective orifice area index at discharge.

A 46-year-old man underwent emergency surgery for heart rupture after acute infarction of the posterior wall. Echocardiography revealed limited myocardial thinning, so rather than sutureless repair, a covering patch was used in view of the risk of recurrent rupture. Postoperative echocardiography showed the myocardial thinning had progressed to a wide defect, and computed tomography demonstrated that the covering patch had prevented a repeat rupture.