Novel Scoring System to Risk Stratify Patients Receiving Durable Left Ventricular Assist Device From J-MACS Registry Data.

BACKGROUND: Recently, destination therapy (DT) was approved in Japan, and patients ineligible for heart transplantation may now receive durable left ventricular assist devices (LVADs). Several conventional risk scores are available, but a risk score that is best to select optimal candidates for DT in the Japanese population remains unestablished.Methods and Results: A total of 1,287 patients who underwent durable LVAD implantation and were listed for the Japanese registry for Mechanically Assisted Circulatory Support (J-MACS) were eligible for inclusion. Finally, 494 patients were assigned to the derivation cohort and 487 patients were assigned to the validation cohort. According to the time-to-event analyses, J-MACS risk scores were newly constructed to predict 3-year mortality rate, consisting of age, history of cardiac surgery, serum creatinine level, and central venous pressure to pulmonary artery wedge pressure ratio >0.71. The J-MACS risk score had the highest predictability of 3-year death compared with other conventional scores in the validation cohort, including HeartMate II risk score and HeartMate 3 risk score. CONCLUSIONS: We constructed the J-MACS risk score to estimate 3-year mortality rate after durable LVAD implantation using large-scale multicenter Japanese data. The clinical utility of this scoring to guide the indication of DT should be validated in the next study.

Robot-Assisted Aortic Valve Replacement　- First Clinical Report in Japan.

BACKGROUND: Robot-assisted valve surgery represents the latest development in the field of minimally invasive approaches. Robotic assistance may provide greater visualization, enhanced dexterity, and greater precision than traditional mini-thoracotomy aortic valve replacement.Methods and Results: Aortic valve replacement operations using the da Vinci Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) were performed on 2 patients, 1 with severe aortic insufficiency and the other with aortic stenosis. Both patients had an uneventful postoperative course and were discharged without any adverse events. CONCLUSIONS: Robot-assisted assisted aortic valve replacement appears feasible and safe in limited cases.

Safe launch of a robotically assisted mitral valve repair program in a single center: experience of initial 20 cases under the Center for Minimally Invasive Surgery.

Robotically assisted mitral valve repair was approved by the Japanese government in April 2018. However, understanding robotic surgery involves steep learning curves of surgeons and dedicated cardiac teams. The Center for Minimally Invasive Surgery (CMIS) of Tottori University Hospital is a multidisciplinary organization established in 2011 with seven surgical departments. In this study, we report strategies for improving the safety of robotic surgery in the CMIS and early results of robotic mitral valve repair at our hospital. We reviewed the first 20 patients who underwent robotic primary mitral valve repair, including concomitant procedures, from October 2019 to September 2021 under the supervision of the CMIS. Before starting the program, the CMIS requires setting console time limit to 180 min and implementing risk management strategies through simulation training for various mechanical failures. Mitral valve repair was completed in all patients. There was no in-hospital or 30-day mortality. No conversion to median sternotomy was necessary. The analysis of mitral pathology revealed 1 case of functional mitral regurgitation, 12 cases of posterior lesions, 3 cases of anterior lesions, 3 cases of bileaflet lesions, and 1 case of commissural lesion. The average cross-clamp time was 133 ± 27 min. Sixteen cases had trace mitral regurgitation postoperatively, and 4 cases had mild mitral regurgitation. The median (interquartile range) postoperative hospital stay was 10 (8.5-12.5) days. Robotically assisted mitral valve repair was performed safely with assistance from the multidisciplinary CMIS, and the early results were satisfactory without compromising clinical outcomes.

Impact of frailty on early and mid-term outcomes of hybrid aortic arch repair.

PURPOSE: The purpose of this study was to investigate the impact of frailty on the clinical outcomes of hybrid aortic arch repair with debranching of the supra-aortic arteries. METHODS: Consecutive patients ≥ 75 years old who underwent hybrid aortic arch repair from January 2010 to December 2019 were retrospectively analyzed. Using the Canadian Study of Health and Aging (CSHA) scale, all patients with a CSHA scale score > 4 were defined as frail. The frail patients (FP) group and the non-frail patients (NFP) group were compared regarding the early and mid-term outcomes of hybrid aortic arch repair. RESULTS: A total of 84 patients were included. The early postoperative results were not markedly different between the groups, except that the rate of transfer to a rehabilitation hospital was higher in the FP group than in the NFP group. The survival at 5 years was significantly lower in the FP group at 43.0% than in the NFP group at 67.7% (P = 0.015). However, the freedom from aorta-related death was not significantly different between the two groups. CONCLUSION: Frailty did not affect the short-term outcomes of hybrid aortic arch repair; however, the mid-term outcomes, including the survival, of the frail patients were significantly worse than those of the non-frail patients, mostly because of non-aorta-related causes.

α1-Adrenergic receptor mediates adipose-derived stem cell sheet-induced protection against chronic heart failure after myocardial infarction in rats.

Cell-based therapy using adipose-derived stem cells (ADSCs) has emerged as a novel therapeutic approach to treat heart failure after myocardial infarction (MI). The purpose of this study was to determine whether inhibition of α1-adrenergic receptors (α1-ARs) in ADSCs attenuates ADSC sheet-induced improvements in cardiac functions and inhibition of remodeling after MI. ADSCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ADSCs, we determined the mRNA levels of vascular endothelial growth factor (VEGF)-A and α1-AR under normoxia or hypoxia and the effects of norepinephrine and an α1-blocker, doxazosin, on the mRNA levels of angiogenic factors. Hypoxia increased α1-AR and VEGF mRNA levels in ADSCs. Norepinephrine further increased VEGF mRNA expression under hypoxia; this effect was abolished by doxazosin. Tube formation of human umbilical vein endothelial cells was promoted by conditioned media of ADSCs treated with the α1 stimulant phenylephrine under hypoxia but not by those of ADSCs pretreated with phenylephrine plus doxazosin. In in vivo studies using rats with MI, transplanted ADSC sheets improved cardiac functions, facilitated neovascularization, and suppressed fibrosis after MI. These effects were abolished by doxazosin treatment. Pathway analysis from RNA sequencing data predicted significant upregulation of α1-AR mRNA expression in transplanted ADSC sheets and the involvement of α1-ARs in angiogenesis through VEGF. In conclusion, doxazosin abolished the beneficial effects of ADSC sheets on rat MI hearts as well as the enhancing effect of norepinephrine on VEGF expression in ADSCs, indicating that ADSC sheets promote angiogenesis and prevent cardiac dysfunction and remodeling after MI via their α1-ARs.

Esm1 and Stc1 as Angiogenic Factors Responsible for Protective Actions of Adipose-Derived Stem Cell Sheets on Chronic Heart Failure After Rat Myocardial Infarction.

BACKGROUND: Although adipose-derived stem cell (ADSC) sheets improve the cardiac function after myocardial infarction (MI), underlying mechanisms remain to be elucidated. The aim of this study was to determine the fate of transplanted ADSC sheets and candidate angiogenic factors released from ADSCs for their cardiac protective actions.Methods and Results:MI was induced by ligation of the left anterior descending coronary artery. Sheets of transgenic (Tg)-ADSCs expressing green fluorescence protein (GFP) and luciferase or wild-type (WT)-ADSCs were transplanted 1 week after MI. Both WT- and Tg-ADSC sheets improved cardiac functions evaluated by echocardiography at 3 and 5 weeks after MI. Histological examination at 5 weeks after MI demonstrated that either sheet suppressed fibrosis and increased vasculogenesis. Luciferase signals from Tg-ADSC sheets were detected at 1 and 2 weeks, but not at 4 weeks, after transplantation. RNA sequencing of PKH (yellow-orange fluorescent dye with long aliphatic tails)-labeled Tg-ADSCs identified mRNAs of 4 molecules related to angiogenesis, including those of Esm1 and Stc1 that increased under hypoxia. Administration of Esm1 or Stc1 promoted tube formation by human umbilical vein endothelial cells. CONCLUSIONS: ADSC sheets improved cardiac contractile functions after MI by suppressing cardiac fibrosis and enhancing neovascularization. Transplanted ADSCs existed for >2 weeks on MI hearts and produced the angiogenic factors Esm1 and Stc1, which may improve cardiac functions after MI.

Prevention of Progression of Aortic Aneurysm by Peptide Vaccine Against Ang II (Angiotensin II) in a Rat Model.

There is no proven medical therapy to inhibit the progression of abdominal aortic aneurysm (AAA) in the clinical setting. To develop a novel therapeutic approach for the treatment of AAA, we focused on vaccination targeting Ang II (angiotensin II) and assessed the effect of an Ang II peptide vaccine on the progression of AAA using a rat model. Ang II peptide was conjugated with KLH (keyhole limpet hemocyanin) carrier protein to induce a sufficient immune response. Male rats were subcutaneously immunized with Ang II-KLH with an adjuvant on days 0, 14, and 28. Aortic dilatation was induced by intraluminal incubation with elastase on day 35. Treatment with Ang II vaccine successfully induced the production of a high titer of anti-Ang II antibodies. Immunization with Ang II vaccine resulted in a significant reduction in expansion of the aortic diameter compared with control rats, without a blood pressure-lowering effect. Four weeks after operation, the increase in Ang II in the aneurysm wall was significantly inhibited by treatment with Ang II vaccine. Inhibition of Ang II action led to suppression of the inflammatory response in the AAA wall through attenuation of the NFκB (nuclear factor kappa B) and c-jun N-terminal kinase signaling cascades. Treatment with Ang II vaccine inhibited accumulation of macrophages in the AAA wall. In addition, expression of TNF-α (tumor necrosis factor alpha) and activation of MMP (matrix metalloproteinase)-2 and MMP-9 were also inhibited by treatment with Ang II vaccine, resulting in protection against the destruction of elastic fibers. This vaccine therapy could become a potent therapeutic option to treat patients with AAA.

Debranching thoracic endovascular aortic repair for distal aortic arch aneurysm in elderly patients aged over 75 years old.

BACKGROUND: We examined the outcome of debranching thoracic endovascular aortic repair (d-TEVAR) without sternotomy for distal aortic arch aneurysm in patients aged ≥75 years. METHODS: Patients who underwent d-TEVAR or TAR for aortic arch aneurysm between 2008 and 2015 at our hospital and aged ≥75 years were included. Age, sex, left ventricular ejection fraction, preoperative creatinine level, diabetes, cerebrovascular disease, and chronic obstructive pulmonary disease were matched using PS. RESULTS: Among 74 patients (d-TEVAR: 51, TAR: 23), 17 patients in each group were matched. No difference in surgical outcome was detected between the d-TEVAR and TAR groups, including 30-day death (0% vs. 0%), hospital death (5.8% vs. 0%: p = 0.31) and incidence of cerebral infarction (5.8% vs. 7.6%: p = 0.27) as well as the long-term outcomes of 5-year survival (92.8% vs. 74.8%: p = 0.30) and 5-year aorta-related event-free rate (88.2% vs. 100%: p = 0.15). Average duration of ICU stay (1.3 ± 1.1 days vs. 5.6 ± 1.3 days: p = 0.025) and hospital stay (16.5 ± 5.2 days vs. 37.7 ± 19.6 days: p = 0.017) were significantly shorter in the d-TEVAR group. CONCLUSION: Our results indicated that d-TEVAR is less invasive without affecting long-term outcome up to 5 years. Although the number of the patients included in the study was small, debranching TEVAR could be one of the treatments of the choice in the elderly, especially with comorbidities.

Tolvaptan can limit postoperative paroxysmal atrial fibrillation occurrence after open-heart surgery.

PURPOSE: Tolvaptan administration in the early postoperative period after cardiac surgery rapidly treats fluid retention without affecting the renal function. Tolvaptan also has the benefit of not stimulating the renin-angiotensin and sympathetic nervous systems, which are risk factors for postoperative paroxysmal atrial fibrillation. In this study, we examined the hypothesis that tolvaptan administration reduces postoperative paroxysmal atrial fibrillation and worsening of the renal function incidence in patients who have undergone open-heart surgery. METHODS: From our previous randomized study, we selected 166 open-heart surgery patients, divided them into 2 groups [tolvaptan group, 83 patients; control (non-tolvaptan) group, 83 patients], and compared the incidence of postoperative paroxysmal atrial fibrillation and worsening of the renal function in the postoperative period between the groups. RESULTS: The incidence of worsening of the renal function was significantly lower in the tolvaptan group than in the control group (4.8% vs. 15.7%; P = 0.04). The incidence of postoperative paroxysmal atrial fibrillation within 14 days was also significantly lower in the tolvaptan group than in the control group (26.5% vs. 42.2%; P = 0.011). CONCLUSION: Tolvaptan administration in the early postoperative period after open-heart surgery may reduce the incidence of postoperative paroxysmal atrial fibrillation and worsening of the renal function.

The second official report from Japanese registry for mechanical assisted circulatory support (J-MACS): first results of bridge to bridge strategy.

BACKGROUND: The Japanese registry for mechanical assisted circulatory support (J-MACS) is a prospective registry to collect all data of implantable left ventricular assist device (LVAD) (and part of paracorporeal VAD) established in 2010. The first analytical report was published in 2017. The organization running J-MACS was used to be the pharmaceuticals and medical devices agency (PMDA), but has been changed to the council for clinical use of ventricular assist device related academic societies in 2017. METHODS: Since 2018, we changed the analytical methods as follows: first, we eliminated paracorporeal VAD from the analysis. Second, we included not only primary implantation but bridge to bridge (BTB) implantation of LVAD. Third, we added the analyses of adverse events that were not included in the previous analysis. RESULTS: As of Oct 2018, 711 primary LVAD implants and 168 BTB implants were enrolled. Survival rate of primary LVAD was 93% at 360 days and 91% at 720 days, and that of BTB was 86% at 360 days and 82% at 720 days. CONCLUSION: We first reported the results of BTB in the second official report of J-MACS. The prognosis after LVAD implantation has been kept good in Japanese circumstances.

ß-Adrenergic Blocker, Carvedilol, Abolishes Ameliorating Actions of Adipose-Derived Stem Cell Sheets on Cardiac Dysfunction and Remodeling After Myocardial Infarction.

BACKGROUND: Treatment of myocardial infarction (MI) includes inhibition of the sympathetic nervous system (SNS). Cell-based therapy using adipose-derived stem cells (ASCs) has emerged as a novel therapeutic approach to treat heart failure in MI. The purpose of this study was to determine whether a combination of ASC transplantation and SNS inhibition synergistically improves cardiac functions after MI.Methods and Results:ASCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ASC cells, mRNA levels of angiogenic factors under normoxia or hypoxia, and the effects of norepinephrine and a ß-blocker, carvedilol, on the mRNA levels were determined. Hypoxia increased vascular endothelial growth factor (VEGF) mRNA in ASCs. Norepinephrine further increased VEGF mRNA; this effect was unaffected by carvedilol. VEGF promoted VEGF receptor phosphorylation and tube formation of human umbilical vein endothelial cells, which were inhibited by carvedilol. In in vivo studies using a rat MI model, transplanted ASC sheets improved contractile functions of MI hearts; they also facilitated neovascularization and suppressed fibrosis after MI. These beneficial effects of ASC sheets were abolished by carvedilol. The effects of ASC sheets and carvedilol on MI heart functions were confirmed by Langendorff perfusion experiments using isolated hearts. CONCLUSIONS: ASC sheets prevented cardiac dysfunctions and remodeling after MI in a rat model via VEGF secretion. Inhibition of VEGF effects by carvedilol abolished their beneficial effects.

Glomerular basement membrane duplication is a predictor of the prognosis of diabetic nephropathy in patients with type 2 diabetes.

BACKGROUND: Several clinical parameters and pathological findings are known to be predictors of the deterioration of diabetic nephropathy (DN). Glomerular basement membrane duplication (GBM-DP) is a pathological feature representing endothelial injury, which is commonly observed in DN. In the present study, we investigated the association between GBM-DP and the renal prognosis in DN. METHODS: The study enrolled 80 patients with renal biopsy-proven DN who were managed at Chiba-East Hospital from 2005 to 2012. We confirmed the pathological findings according to the Renal Pathology Society classifications, and we further evaluated the GBM-DP, which was defined as double contours of the GBM that expanded more than 10% of capillary loops in the most affected nonsclerotic glomerulus. We used Cox regression models to estimate hazard ratios (HRs) for end-stage renal disease (ESRD), with adjustment for age, sex, systolic blood pressure, HbA1c, estimated glomerular filtration rate (eGFR), and urinary protein excretion (UP) at baseline. RESULTS: Of the 80 patients, 56 were male (70.0%) and the mean age was 59.1 years. The median eGFR and UP were 42 ml/min/1.73 m2 (IQR 30, 59) and 3.1 g/gCr (IQR 1.2, 5.2). Twenty-seven patients progressed to ESRD and one patient died during the median observational period of 2.9 years (IQR 1.5, 4.3). The multivariable analyses showed that GBM-DP was significantly associated with ESRD (HR 3.18 [95% confidence interval (CI): 1.02-9.87], p = 0.045). CONCLUSION: We newly identified GBM-DP as a strong prognostic predictor in DN patients. Further study is needed to clarify the pathogenic mechanism of GBM-DP in DN.

Pretreatment with an angiotensin II receptor blocker abolished ameliorating actions of adipose-derived stem cell sheets on cardiac dysfunction and remodeling after myocardial infarction.

INTRODUCTION: Cell sheets using myoblasts have been developed for the treatment of heart failure after myocardial infarction (MI) bridging to heart transplantation. Stem cells are supposed to be better than myoblasts as a source of cells, since they possess a potential to proliferate and differentiate into cardiomyocytes, and also have capacity to secrete angiogenic factors. Adipose-derived stem cells (ASCs) obtained from fat tissues are expected to be a new cell source for ASC sheet therapies. Administration of angiotensin II receptor blockers (ARBs) is a standard therapy for heart failure after MI. However, it is not known whether ARBs affect the cell sheet therapy. This study aimed to examine ameliorating effects of ASC sheets on heart failure and remodeling after MI, and how pretreatment with ARBs prior to the creation of MI and ASC sheet transplantation modifies the effects of ASC sheets. METHODS: ASCs were isolated from fat tissues of wild-type rats, and ASC sheets were engineered on temperature-responsive dishes. In in vitro studies using cultured cells, mRNA levels of vascular endothelial growth factor (VEGF) in ASCs were determined by RT-PCR in the presence of angiotensin II and/or an ARB, irbesartan, under normoxia and hypoxia; mRNA and protein levels of angiotensin II receptor type 1a (AT1aR), type 1b (AT1bR) and type 2 (AT2R) were also determined by RT-PCR and western blotting. In in vivo studies using a rat MI model, effects of transplanted ASC sheets and/or irbesartan on cardiac functions and remodeling after MI were evaluated by echocardiography, histological analysis and molecular biological techniques. RESULTS: In the in vitro studies, ASCs expressed higher levels of VEGF mRNA under hypoxia. They also expressed mRNA and protein of AT1aR but not AT1bR or AT2R. Under normoxia, angiotensin II increased the level of VEGF mRNA in ASCs, which was abolished by irbesartan. Under hypoxia, irbesartan reduced the level of VEGF mRNA in ASCs regardless of whether angiotensin II was present or not. In the in vivo studies, ASC sheets improved cardiac functions after MI, leading to decreased interstitial fibrosis and increased capillary density in border zones. These effects of ASC sheets were abolished by oral administration of irbesartan before MI and their transplantation. CONCLUSIONS: ASC sheets ameliorated cardiac dysfunctions and remodeling after MI via increasing VEGF expression, which was abolished by pretreatment with irbesartan before the creation of MI and transplantation.

Can Tolvaptan Protect Renal Function in the Early Postoperative Period of Cardiac Surgery?　- Results of a Single-Center Randomized Controlled Study.

BACKGROUND: Oral administration of tolvaptan, a vasopressin V2receptor antagonist, significantly reduces deterioration of renal function, which has recently been highlighted as an exacerbating factor for adverse events in patients with acute heart failure. In the present study we tested the hypothesis that concomitant administration of tolvaptan with a conventional diuretic is beneficial for perioperative body fluid management in patients who have undergone cardiac surgery.Methods and Results:In all, 280 patients who underwent cardiac surgery were prospectively randomized to concomitant treatment with tolvaptan and a conventional diuretic (tolvaptan group; 147 patients) or treatment with a conventional diuretic alone (control group; 133 patients). Groups were compared in terms of the time required to restore preoperative body weight and the incidence of worsening renal function (WRF), defined as an increase in the serum creatinine level ≥0.3 mg/dL. The time required to restore preoperative body weight was significantly shorter in the tolvaptan than control group (mean [±SD] 3.97±1.95 vs. 5.02±2.83 days, respectively; P<0.001). The incidence of WRF was significantly lower in the tolvaptan than control group (n=11 [7.5%] vs. n=25 [18.8%], respectively; P=0.011). CONCLUSIONS: Administration of tolvaptan with conventional diuretics in the early postoperative period after cardiac surgery could be beneficial in maintaining urine output without affecting renal function and may thus help avoid WRF.

Novel temporary left ventricular assist system with hydrodynamically levitated bearing pump for bridge to decision: initial preclinical assessment in a goat model.

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. We developed a new temporary left ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing. We used three adult goats (body weight, 58-68 kg) to investigate the 30-day performance and hemocompatibility of the newly developed left ventricular assist system, which included the pump, inflow and outflow cannulas, the extracorporeal circuit, and connectors. Hemodynamic, hematologic, and blood chemistry measurements were investigated as well as end-organ effect on necropsy. All goats survived for 30 days in good general condition. The blood pump was operated at a rotational speed of 3000-4500 rpm and a mean pump flow of 3.2 ± 0.6 L min. Excess hemolysis, observed in one goat, was due to the inadequate increase in pump rotational speed in response to drainage insufficiency caused by continuous contact of the inflow cannula tip with the left ventricular septal wall in the early days after surgery. At necropsy, no thrombus was noted in the pump, and no damage caused by mechanical contact was found on the bearing. The newly developed temporary left ventricular assist system using a disposable centrifugal pump with hydrodynamic bearing demonstrated consistent and satisfactory hemodynamic performance and hemocompatibility in the goat model.

Sewing needles in the abdominal cavity assumed to have been ingested and to have penetrated the GI tract 40 years ago: A case report.

A 60-year old woman had been hospitalized in a psychiatric hospital for 40 years for schizophrenia. An X-ray was performed when she fell, which showed needles in the abdominal field. After additional examinations and questioning, the patient was diagnosed with needles in the abdominal cavity, which were assumed to have been ingested and to have perforated the GI tract 40 years ago. They were removed by laparoscopic surgery. The needles were found in the omentum and near the left ovary. There were no inflammatory reactions around them. There have been previous reports about the removal of intra-abdominal foreign bodies, but foreign body reaction occurred in most of the reports. Our case had the longest period from ingestion of the foreign bodies to their removal. Laparoscopy and intraoperative fluoroscopy are useful for removing intra-abdominal foreign bodies because of their ability to help discriminate between structures and to navigate in real time.

Successful multimodality treatment for locally advanced primary thymic adenocarcinoma: report of a case.

Although the optimal treatment strategy for locally advanced thymic carcinomas has yet to be determined, complete resection of the tumor after induction chemoradiotherapy (CRT) can sometimes provide a good chance of being cured. A 61-year-old woman was diagnosed with locally advanced primary thymic carcinoma, which invaded bilateral brachiocephalic veins and superior vena cava with intraluminal tumor thrombus. Induction CRT was performed, and a partial response to the treatment was achieved. Subsequent radical surgery was successfully performed by the median full sternotomy with a right transmanubrial osteomuscular sparing approach (TMA). The patient is currently alive and has remained disease-free for a year. The TMA is useful for extensive surgery of locally advanced thymic carcinoma because it can provide good exposure of the operative field without post-operative functional limitation of upper limbs.

Smooth muscle cell sheet transplantation preserve cardiac function and minimize cardiac remodeling in a rat myocardial infarction model.

BACKGROUND: We examined whether a vascular smooth muscle cell (SMC) sheet is effective in the treatment of a rat myocardial infarction (MI) model. METHODS: We examined the effect of SMC sheet on the cardiac function and cardiac remodeling in a rat MI model in comparison with their effect of dermal fibroblast (DFB) sheet in vivo. Furthermore, we estimated the apoptosis and secretion of angiogenic factor of SMC under hypoxic condition in comparison with DFB. Seven days after MI, monolayer cell sheets were transplanted on the infarcted area (SMC transplantation group, SMC-Tx; DFB transplantation group, DFB-Tx; no cell sheet transplantation group, Untreated; neither MI nor cell sheet transplantation group, Sham). We evaluated cardiac function by echocardiogram, degree of cardiac remodeling by histological examination, and secretion of angiogenic growth factor by enzyme immunoassay. RESULTS: Twenty-eight days after transplantation, SMC-Tx showed the following characteristics compared with the other groups: 1) significantly greater fractional area shortening (SMC-Tx, 32.3 ± 2.1 %; DFB-Tx, 23.3 ± 2.1 %; untreated, 25.1 ± 2.6 %), 2) suppressed left ventricular dilation, smaller scar expansion, and preserved wall thickness of the area at risk and the posterior wall, 3) decreased fibrosis, preserved myocardium in the scar area, and greater number of arterioles in border-zone, 4) tight attachment of SMC sheets on the scarred myocardium, and less apoptotic cell death. In in vitro experiments, SMCs secreted higher amounts of basic fibroblast growth factor (SMC, 157.7 ± 6.4 pg/ml; DFB, 3.1 ± 1.0 pg/ml), and showed less apoptotic cell death under hypoxia. CONCLUSIONS: Our results illustrate that transplantation of SMC sheets inhibited the progression of cardiac remodeling and improve cardiac function. These beneficial effects may be due to superior SMC survival.