Masaya Takahashi

Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells

Various cytokines produced by bone marrow cells can protect adult cardiomyocytes against apoptosis. Thus, we investigated the feasibility of implanting adult cardiomyocytes in combination with bone marrow cells for myocardial repair. Ventricular cardiomyocytes were isolated from adult rats and cocultured with bone marrow cells. Using a rat model of doxorubicin-induced cardiomyopathy, we injected 6 × 105 adult cardiomyocytes, 3 × 107 bone marrow cells, or both into damaged hearts, for myocardial repair. Coculture of the cardiomyocytes with the bone marrow cells enhanced the expression of integrin-β1D and focal adhesion kinase in cardiomyocytes, resulting in increased survival and decreased apoptosis of the cardiomyocytes after 7 days of culture. Compared with the baseline levels, cardiac function was preserved by the implantation of bone marrow cells alone and by the implantation of cardiomyocytes in combination with bone marrow cells, but it was decreased significantly 28 days after the implantation of cardiomyocytes alone. Furthermore, apoptosis of the host cardiomyocytes was decreased significantly after the implantation of bone marrow cells alone, or in combination with cardiomyocytes, compared with that after the implantation of cardiomyocytes alone (p < 0.01). Interestingly, the implantation of adult cardiomyocytes in combination with bone marrow cells resulted in a dramatic increase in the survival of donor cardiomyocytes, and induced the myogenic differentiation of donor bone marrow stem cells. Our findings indicate that cardiomyocytes and bone marrow cells can assist and compliment each other; thus, the implantation of adult cardiomyocytes in combination with bone marrow cells shows promise as a feasible new strategy for myocardial repair.

Comparison of cell therapy and cytokine therapy for functional repair in ischemic and nonischemic heart failure.

Although cell therapy shows great promise as a new therapeutic strategy for heart failure, its precise mechanisms remain unclear. Furthermore, the advantages of cell therapy over conventional cytokine therapy have yet to be clarified. This study was designed to compare the functional improvement achieved by cell therapy and cytokine therapy in both ischemic and nonischemic heart failure experimental models. Ischemic heart failure was induced by ligating the left anterior descending artery, and nonischemic heart failure was induced by an IP injection of doxorubicin, respectively, in mice. After establishing the heart failure models, mice were randomly given a single intramyocardial injection of 2 × 105 c-kit-positive bone marrow stem cells (cell therapy), hepatic growth factor (cytokine therapy), or PBS injection only (control). In the ischemic heart failure model, both cell therapy and cytokine therapy increased the vessel density significantly, inhibited apoptosis of myocytes, and decreased the fibrotic area in the ischemic myocardium, which resulted in a significant increase in the survival rate and enhancement of the cardiac function of these mice (p < 0.05 vs. control therapy). In the nonischemic heart failure model, significant increases in the survival rate and cardiac function were achieved by cell therapy (p < 0.05 vs. control therapy), but not by cytokine therapy, although cytokine therapy inhibited the fibrosis and apoptosis of the cardiomyocytes. Both cell therapy and cytokine therapy are alternative treatments for ischemic heart failure. However, cell therapy is more effective for the treatment of nonischemic heart failure than cytokine therapy achieved by the administration of a single growth factor.

Aortic arch surgery in octogenarians: is it justified?

OBJECTIVESnElderly patients are sometimes denied aortic arch surgery because of the perception of poor outcomes and an unacceptable quality of life (QOL). In this study, we evaluated the early clinical outcomes, long-term survival and QOL following surgical treatment for aortic arch disease in octogenarian patients.nnnMETHODSnA total of 47 consecutive patients over the age of 80 years were referred to our institutions. Of these patients, 20 underwent surgical intervention (surgical group) and 27 were treated medically (medical group). Kaplan-Meier survival analysis was performed between the two groups, and the results were compared with age-matched population data. The risk factors for mortality were determined using a Cox regression analysis. A QOL assessment was performed using the 36-item Short Form Health Survey.nnnRESULTSnThe patient characteristics at baseline were not significantly different between the two groups. In the surgical cases, conventional total aortic arch replacement was performed in 15 patients, debranched thoracic endovascular aortic repair (TEVAR) in 2 and chimney TEVAR in 3. Emergency procedures were performed in 3 patients. No hospital deaths occurred in the surgical groups. Reoperation for bleeding was required in 2 patients, and prolonged mechanical ventilation was required in 4 patients. The 5-year survival was 61.5% in the surgical group and 14.2% in the medical group (P = 0.02). Freedom from aorta-related death at 5 years was 92.3% in the surgical group and 32.3% in the medical group (P = 0.01). There were no differences in the 5-year survival between patients undergoing surgical intervention and the sex- and age-matched population (P = 0.80), whereas the 5-year survival was significantly lower in patients who received medical therapy relative to the sex- and age-matched population (P < 0.001). Medical therapy was the sole risk factor for mortality (hazard ratio: 3.16, P = 0.04). Among the survivors at mid-term, the quality-of-life measures were similar between those in the surgical group and those in the medical group.nnnCONCLUSIONSnSurgical intervention for aortic arch disease in octogenarians can yield satisfactory early clinical outcomes and acceptable mid-term survival with adequate daily activity. This study indicates that among octogenarians, age alone should not disqualify a patient from receiving an aortic arch intervention.

Transapical extirpation of a left ventricular thrombus in takotsubo cardiomyopathy

A 58-year-old Japanese female was referred to our hospital. Although the electrocardiogram showed ST elevation, coronary angiography showed intact coronary artery. We diagnosed Takotsubo cardiomyopathy and a left ventricular thrombus. Anticoagulation was administered; however, the left ventricular thrombus had become mobile and protrusive. We extirpated the left ventricular thrombus via trans-apical approach. Left ventricular thrombus is rare in Takotsubo cardiomyopathy, but these patients are at a higher risk of thromboembolism, especially if the thrombi are mobile and protruding.

Mortality and Morbidity After Total Aortic Arch Replacement

BACKGROUNDnTotal aortic arch replacement is associated with considerable mortality and morbidity. Although operative death is the most extreme adverse clinical end point, postoperative morbidity can also be devastating for survivors.nnnMETHODSnWe examined the short-term and long-term outcomes of 146 patients who underwent total aortic arch replacements between September 2003 and September 2011.nnnRESULTSnThe overall in-hospital mortality was 4.8%, and major postoperative morbidity during hospitalization occurred in 29 patients (19.9%). Multivariate analyses demonstrated that risk factors for hospital death were left thoracotomy (odds ratio [OR], 51.92; p=0.01), high preoperative serum creatinine values (OR, 3.88; p=0.02), and intraoperative blood loss (OR, 1.01; p=0.04). Ruptured aorta (OR, 7.13; p=0.02) and previous myocardial infarction (OR, 5.13; p=0.04) were identified as independent risk factors for major postoperative morbidity. The postoperative survival of all patients at 5 years was 76.7%±5%. After hospital discharge, the standardized mortality ratios showed no significant difference between hospital survivors and a comparable Japanese population and were 1.09 (p=0.41) among patients without major morbidity and 1.82 (p=0.12) among those with major morbidity. The development of renal failure requiring hemodialysis increased the risk of long-term death (hazard ratio, 5.59; p=0.03), even among hospital survivors.nnnCONCLUSIONSnOur approach for total arch replacement resulted in low in-hospital mortality and morbidity. Long-term outcomes are stable in hospital survivors, especially in the absence of a postoperative requirement for dialysis.

Valve replacement for papillary fibroelastoma involving the mitral valve chordae.

Primary cardiac tumors are relatively rare, and 75% are benign histologically. Of these benign tumors, papillary fibroelastoma is the second most common after myxoma [1]. Most cases can be treated with a single excision, and few cases warrant valve replacement. An 85-year-old man with a 4-year history of paroxysmal atrial fibrillation that was treated medically was referred for a left ventricle tumor detected using echocardiography. The 18 25-mm tumor at the mitral valve chordae was heterogeneous, with clear borders (Fig 1). Myxoma was diagnosed, and surgery was performed. The left atrium was approached with the right side dissected. The tumor could be observed through the mitral valve and was found to involve the chordate extending from the posterior papillary muscle to the anterior cusp (Fig 2). Resection of only the tumor was impossible. In addition to the tumor, the anterior mitral cusp and chordae were excised, and mitral valve replacement was performed. The sampled papillary tumor formed a sea anemone–like mass with multiple avascular collagenous fronds (Fig 3). The histopathologic diagnosis confirmed a papillary fibroelastoma. The postoperative course was uncomplicated.

Relief of vasospasm with fasudil after off-pump coronary artery bypass grafting: a case study

BackgroundCoronary vasospasm after coronary artery bypass grafting (CABG) is a rare but potentially lethal complication. It is often refractory to several vasodilators. We report a case of refractory coronary vasospasm relieved by fasudil injection.Case presentationA 74-year-old woman who had three instances of in-stent stenosis at the left anterior descending artery (LAD) was referred for CABG treatment. Preoperative coronary angiography showed 90% in-stent stenosis of the proximal LAD and 75% stenosis of the diagonal branch. We performed a left internal thoracic artery (LITA)-LAD bypass and a right internal thoracic artery (RITA) diagonal branch bypass. After anastomosis, transit time flow measurement revealed poor blood flow of LITA-LAD bypass even after re-anastomosis. We performed coronary angiography and detected a vasospasm in the native coronary arteries, which was not relieved using conventional vasodilators (calcium channel blockers, isosorbide dinitrate, and nicorandil) However, we were able to relieve the coronary vasospasm by administering fasudil (a Rho kinase inhibitor) injection without causing systemic hypotension.ConclusionsFasudil may be an important vasodilator, especially in cases of coronary vasospasm after CABG.

Localized Doxorubicin-Induced Cardiomyopathy Complicated With Shower Emboli Originating From Apical Intramural Thrombi

Received November 17, 2017; revised manuscript received December 26, 2017; accepted January 9, 2018; released online February 20, 2018 Time for primary review: 17 days Department of Medicine and Clinical Science (H.I., S.K., S.O., T.O., M.Y.), Department of Radiology (M.O.), Department of Surgery and Clinical Science (M.T., A.M., K.H.), Yamaguchi University Graduate School of Medicine, Ube; Department of Internal Medicine, Asahi University School of Dentistry, Mizuho (G.T.), Japan Mailing address: Shigeki Kobayashi, MD, PhD, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan. E-mail: skoba@yamaguchi-u.ac.jp ISSN-1346-9843 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp Localized Doxorubicin-Induced Cardiomyopathy Complicated With Shower Emboli Originating From Apical Intramural Thrombi

1-Year Follow-Up of Contained Aortic Root Rupture After Transcatheter Aortic Valve Replacement

The authors performed a transfemoral aortic valve replacement (TF-TAVR) in an 89-year-old woman with severe aortic stenosis. The pre-operative transthoracic echocardiography (TTE) revealed severe aortic stenosis (aortic valve area 0.6 cm2) with huge calcifications at each leaflet. At multislice

Coronary obstruction occurring 72 h after transcatheter aortic valve replacement with a self-expandable valve

Article history: Received 6 July 2016 Accepted 5 August 2016 Available online 07 August 2016 tive valve close to the LCA ostium. After dilation using a 20-mmballoon, paravalvular leakage was reduced from moderate to mild without any significant findings of myocardial ischemia. Her hemodynamic status was stable and final aortography showed no coronary flow impairment (Fig. 1). Three days after TAVR, she complained of sudden strong dyspnea.