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1.
Artigo em Inglês | MEDLINE | ID: mdl-34580812

RESUMO

An 86-year-old woman with severe aortic stenosis was thought to be at a high risk for surgical aortic valve replacement and inoperability due to old age and porcelain aorta. Furthermore, transcatheter aortic valve replacement (TAVR) was considered difficult due to high risk of coronary obstruction secondary to the aortic root anatomy and poor vascular access associated with marked atherosclerotic lesions on the distal aortic arch with peripheral artery disease. We successfully treated her with TAVR via the brachiocephalic artery in combination with prophylactic off-pump coronary artery bypass grafting.

2.
Ann Thorac Surg ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34534528

RESUMO

BACKGROUND: This study aimed to clarify the incidence and determinants of postoperative adverse events in patients with ischemic cardiomyopathy who achieved long-term durable mitral valve repair. METHODS: Between 1999 and 2015, 166 patients with chronic ischemic mitral regurgitation (MR) and left ventricular (LV) ejection fraction ≤40% underwent restrictive mitral annuloplasty. During follow-up (65±34 months), echocardiographic assessments were performed 809 times (mean, 4.9±2.4 times) and 20 patients who had developed postoperative recurrent MR (≥moderate) were excluded. Finally, 146 patients (68±9 years) whose MR was well controlled over time were included. RESULTS: A total of 61 mortalities and/or 27 readmissions for heart failure were observed in 76 patients (52%). Among hospital survivors, age (adjusted hazard ratio: 1.05; P=0.001), and estimated glomerular filtration rate (adjusted hazard ratio: 0.61; P=0.001) were identified as independent predictors of long-term mortality and/or readmission for heart failure. The degree of LV function recovery after surgery was comparable between patients with and without adverse events. However, the former group showed greater values for systolic pulmonary artery pressure, tricuspid regurgitation severity, inferior vena cava dimension, and plasma brain natriuretic peptide level throughout the follow-up period (group effect p<0.05 for all). CONCLUSIONS: Approximately 50% of patients died or were hospitalized for heart failure even in the absence of recurrent mitral regurgitation during the 5-year follow-up, indicating that durable mitral repair does not always lead to favorable clinical outcomes. The adverse events might be related to volume overload secondary to impaired renal function and less favorable pulmonary hemodynamics.

3.
Mol Ther Methods Clin Dev ; 22: 338-349, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34514026

RESUMO

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used for cardiac safety assessment but have limitations for the evaluation of drug-induced contractility. Three-dimensional (3D) cardiac tissues are similar to native tissue and valuable for the assessment of contractility. However, a longer time and specialized equipment are required to generate 3D tissues. We previously developed a simple method to generate 3D tissue in a short period by coating the cell surfaces with extracellular matrix proteins. We hypothesized that this 3D cardiac tissue could be used for simultaneous evaluation of drug-induced repolarization and contractility. In the present work, we examined the effects of several compounds with different mechanisms of action by cell motion imaging. Consequently, human ether-a-go-go-related gene (HERG) channel blockers with high arrhythmogenic risk caused prolongation of contraction-relaxation duration and arrhythmia-like waveforms. Positive inotropic drugs, which increase intracellular Ca2+ levels or myocardial Ca2+ sensitivity, caused an increase in maximum contraction speed (MCS) or average deformation distance (ADD) (ouabain, 138% for MCS at 300 nM; pimobendane, 132% for ADD at 3 µM). For negative inotropic drugs, verapamil reduced both MCS and ADD (61% at 100 nM). Thus, this 3D cardiac tissue detected the expected effects of various cardiovascular drugs, suggesting its usefulness for cardiotoxicity evaluation.

4.
Circ J ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526438

RESUMO

BACKGROUND: This study retrospectively evaluated the long-term patient outcomes and durability of the Mosaic mitral porcine bioprosthesis in the Japan Mosaic valve long-term multicenter study.Methods and Results:The medical records of 390 patients who underwent mitral valve replacement with the Mosaic bioprosthesis at 10 centers in Japan (1999-2014) were reviewed. Patient data were collected using the Research Electronic Data Capture software. Patient survival was determined using the Kaplan-Meier method. Freedom from structural valve deterioration (SVD) and valve-related reoperation and death were determined using actuarial methods. The median (interquartile range [IQR]) age of the cohort was 73 (69-77) years. The median (IQR) follow-up period was 4.83 (1.84-8.26) years. The longest follow-up period was 15.8 years. The 30-day mortality rate was 5.4%. The 12-year actuarial survival rate was 54.1±4.5%, and the freedom from valve-related death was 85.3±3.4%. The freedom from reoperation at 12 years was 74.3±5.7%. The freedom from SVD at 12 years was 81.4±6.6% for patients aged ≥65 years and 71.6±11.1% for those aged <65 years. The median (IQR) mean pressure gradient was 4.1 (3.0-6.0) and 5.6 (4.0-6.7) mmHg at 1 and 10 years, respectively. The median (IQR) effective orifice area was 1.7 (1.4-2.0) and 1.4 (1.2-1.6) cm2at 1 and 10 years, respectively. CONCLUSIONS: The Mosaic porcine bioprosthesis offered satisfactory long-term outcomes for up to 12 years.

5.
Circ J ; 85(10): 1906-1917, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34433758

RESUMO

Destination therapy (DT) is the indication to implant a left ventricular assist device (LVAD) in a patient with stage D heart failure who is not a candidate for heart transplantation. The implantable LVAD has been utilized in Japan since 2011 under the indication of bridge to transplant (BTT). After almost 10 year lag, DT has finally been approved and reimbursed in May 2021 in Japan. To initiate the DT program in Japan, revision of the LVAD indication from BTT is necessary. Also, in-depth discussion of caregiver issues as well as end-of-life care is indispensable. For that purpose, we assembled a DT committee of multidisciplinary members in August 2020, and started monthly discussions via web-based communication during the COVID-19 pandemic. This is a summary of the consensus reached after 6 months' discussion, and we have included as many relevant topics as possible. Clinical application of DT has just started, and we are willing to revise this consensus to meet the forthcoming issues raised during real-world clinical experience.


Assuntos
COVID-19/epidemiologia , Consenso , Insuficiência Cardíaca/terapia , Transplante de Coração , Coração Auxiliar , Pandemias , SARS-CoV-2 , Insuficiência Cardíaca/epidemiologia , Humanos , Japão/epidemiologia
6.
Ann Vasc Surg ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34461238

RESUMO

BACKGROUND: Although the preoperative risk factors associated with the occurrence of type II endoleak (ETII) after endovascular aortic repair (EVAR) have gradually become more evident, the preoperative risk factors associated with aneurysm sac enlargement caused by ETII remain unclear. This study aimed to determine the preoperative risk factors associated with aneurysm sac enlargement caused by ETII after EVAR. METHODS: This retrospective cohort study reviewed 519 EVARs performed for true abdominal aortic aneurysm between January 2006 and December 2018 at our institution. EVARs using commercially available bifurcated devices with no type I or III endoleaks during follow-up and with ≥12 months follow-up were included. A total of 320 patients were enrolled in the study. To identify the preoperative risk factors of sac enlargement after EVAR, Cox regression analysis was used to assess preoperative data. RESULTS: The median follow-up period was 60.8 months. Overall, 135 of 320 patients (42%) had ETII during follow-up, and 47 of 135 patients (35%) developed aneurysm sac enlargement. Multivariate analysis revealed that chronic kidney disease (CKD) stage ≥4 (hazard ratio [HR], 4.65; 95% confidence interval [CI], 2.13-10.15; P = 0.001), patent inferior mesenteric artery (IMA) (HR, 17.85; 95% CI, 2.46-129.73; P< 0.001), and number of patent lumbar arteries (LAs) (HR, 1.37; 95% CI, 1.13-1.68; P= 0.002) were risk factors of aneurysm sac enlargement caused by ETII. CONCLUSIONS: CKD stage ≥4, patent IMA, and number of patent LAs were independent risk factors for aneurysm sac enlargement after EVAR. In particular, patent IMA had the highest HR and seemed to have the greatest impact on long-term aneurysm sac enlargement. Hence, taking preoperative measures to address a patent IMA appears to be important in reducing the incidence of sac enlargement.

7.
Biochem Biophys Res Commun ; 574: 91-96, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34450429

RESUMO

A major concern in the clinical application of induced pluripotent stem cells (iPSCs) is the prevention of tumorigenesis after implantation. Stem cells with high proliferative and differentiation potential are sensitive to radiation. Therefore, we hypothesized that irradiation may selectively eliminate residual undifferentiated human iPSCs (hiPSCs) in a cell population containing differentiated cardiomyocytes derived from hiPSCs (hiPSCs-CMs) and thus reduce tumorigenicity in vivo. hiPSC-CMs were irradiated with X-rays, after which the cell proliferation, apoptosis, morphology, and gene expression were analyzed. The gene expression of Lin28A, Nanog, Oct3/4, and SRY-box 2 was significantly lower in the irradiation group than in the control group. Irradiated hiPSC-CMs showed no change in proliferation potency and morphology compared to untreated hiPSC-CMs. Furthermore, irradiation did not induce apoptosis of differentiated cardiomyocytes. No significant difference in the gene expression of cardiac-specific markers, including α-myosin heavy chain, cardiac troponin T, and NK2 Homeobox 5, was observed between the groups. Tumorigenicity tests using NOG mice showed less frequent tumor formation in the irradiation group than in the control group. Irradiation of hiPSC-CMs significantly reduced the number of undifferentiated hiPSC and the tumor formation, while minimizing any adverse effects on hiPSC-CMs, thereby enabling safe hiPSC-based treatment.

8.
J Cardiol ; 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34348863

RESUMO

BACKGROUND: Dialysis patients with aortic stenosis are generally considered as being at extreme or high surgical risk. Herein, the first clinical trial was conducted to investigate clinical safety and effectiveness of transcatheter aortic valve replacement (TAVR) using the balloon-expandable transcatheter aortic valve (SAPIEN 3, Edwards Lifesciences, Irvine, CA, USA) in Japanese dialysis patients. METHODS: The clinical trial is a single arm, prospective, open, non-randomized, Japanese multicenter study. The primary purpose of this trial is to evaluate the efficacy and safety of TAVR using SAPIEN 3 in 28 Japanese dialysis patients. RESULTS: Mean age was 79.2 years and 67.9% were male (Mean STS score was 14.3%). Transfemoral and transapical approaches were performed in 25 (89.3%) and 3 patients (10.7%), respectively. All bioprostheses were successfully implanted. Median intensive care unit stay and hospital stay after TAVR were 1.4 days and 6.3 days, respectively. In-hospital mortality was 3.6% and freedom from all-cause mortality at 1 year was 89.3%. Disabling stroke and life-threatening bleeding at 1 year was 7.7% and 8.5%, respectively. There was no structural valve deterioration during follow-up. New York Heart Association functional status, six-minute walk test, and EuroQOL visual analogue scale score significantly improved through 1 year compared with baseline. CONCLUSIONS: TAVR using SAPIEN 3 is safe and effective for the treatment of Japanese dialysis patients with symptomatic severe aortic valve stenosis.

9.
Methods Mol Biol ; 2320: 23-27, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34302644

RESUMO

Regenerative medicine using human-induced pluripotent stem cells (hiPSCs) is a promising approach to treat heart failure. However, a large number of cells are required to achieve the desired therapeutic effect. The stirring-type suspension culture method allows a large-scale production of hiPSC-derived cardiomyocytes (more than 1 × 108 cells/100 mL), leading to a stable cell supply. Here, we describe a method to scale-up hiPSC-derived cardiomyocyte production with a high differentiation efficiency.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Animais , Técnicas de Cultura de Células/métodos , Células Cultivadas , Humanos , Camundongos
10.
Methods Mol Biol ; 2320: 29-33, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34302645

RESUMO

The human adult heart consists of approximately four billion cardiomyocytes, which do not possess self-renewal abilities. Severe myocardial infarction and dilated cardiomyopathy result in the loss of more than a billion cardiomyocytes. Induced pluripotent stem cells (iPSCs) can differentiate into various types of cells. Due to this ability, these cells could potentially serve as a new resource for cell therapy. Many studies have utilized cardiomyocytes derived from iPSCs for myocardial regeneration therapy. To obtain large number of cardiomyocytes for transplantation, we need to develop effective methods that would allow us to dissociate multiple cardiomyocyte aggregates simultaneously. Here, we describe a method to efficiently dissociate large number of iPSC-derived cardiomyocyte aggregates.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Diferenciação Celular/fisiologia , Células Cultivadas , Humanos , Infarto do Miocárdio/terapia
11.
Methods Mol Biol ; 2320: 65-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34302648

RESUMO

In this chapter, we introduce the method for fabricating thick and anisotropic cardiac tissue for heart regeneration. Aligned and biodegradable nanofiber can be prepared by electrospinning Food and Drug Administration-approved poly (lactic-co-glycolic acid) on a rotating drum. After the nanofibers are transferred on to a polydimethylsiloxane frame, the cardiomyocytes could be plated on the nanofiber to form thick and anisotropic cardiac tissue rapidly. Cardiac tissue-like construct could be easily created by one-step method, and transplanted onto the hearts of myocardium infarction models and lead to their functional recovery.


Assuntos
Infarto do Miocárdio/terapia , Miócitos Cardíacos/citologia , Nanofibras/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Anisotropia , Células Cultivadas , Masculino , Miocárdio/citologia , Ratos , Ratos Nus , Engenharia Tecidual/métodos , Tecidos Suporte/química
12.
Methods Mol Biol ; 2320: 75-79, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34302649

RESUMO

Myocardial tissues in vivo are complex three-dimensional structures. Significant efforts are currently focused on developing functionally and structurally similar tissues in vitro to transplant them for regenerative therapy and to evaluate pharmacological agents. We describe a method for constructing three-dimensional multilayered cardiac tissues by coating cells with extracellular matrix components (ECM).


Assuntos
Miócitos Cardíacos/citologia , Células Cultivadas , Matriz Extracelular/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Miocárdio/citologia , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos
13.
J Am Heart Assoc ; 10(13): e008649, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34212772

RESUMO

Background Clinical effectiveness of autologous skeletal cell-patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy. Methods and Results Twenty-four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% on optimal medical therapy were enrolled. Autologous cell patches were implanted over the surface of the left ventricle through left minithoracotomy without procedure-related complications and lethal arrhythmia. We identified 13 responders and 11 nonresponders using the combined indicator of a major cardiac adverse event and incidence of heart failure event. In the responders, symptoms, exercise capacity, and cardiac performance were improved postoperatively (New York Heart Association class II 7 [54%] and III 6 [46%] to New York Heart Association class II 12 [92%] and I 1 [8%], P<0.05, 6-minute walk test; 471 m [370-541 m] to 525 m [425-555 m], P<0.05, left ventricular stroke work index; 31.1 g·m2·beat [22.7-35.5 g·m2·beat] to 32.8 g·m2·beat [28-38.5 g·m2·beat], P=0.21). However, such improvement was not observed in the nonresponders. In responders, the actuarial survival rate was 90.9±8.7% at 5 years, which was superior to the estimated survival rate of 70.9±5.4% using the Seattle Heart Failure Model. However, they were similar in nonresponders (47.7±21.6% and 56.3±8.1%, respectively). Multivariate regression model with B-type natriuretic peptide, pulmonary capillary wedge pressure, and expression of histone H3K4me3 (H3 lysine 4 trimethylation) strongly predicted the responder of this treatment (B-type natriuretic peptide: odds ratio [OR], 0.96; pulmonary capillary wedge pressure: ​OR, 0.58; H3K4me3: OR, 1.35, receiver operating characteristic-area under the curve, 0.96, P<0.001). Conclusions This clinical trial demonstrated that autologous skeletal stem cell-patch implantation might promise functional recovery and good clinical outcome in selected patients with nonischemic dilated cardiomyopathy, in addition to safety and feasibility. Registration URL: http://www.umin.ac.jp/english/. Unique identifiers: UMIN000003273, UMIN0000012906 and UMIN000015892.

14.
Sci Rep ; 11(1): 14698, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282197

RESUMO

In contrast to hypertrophic cardiomyopathy, there has been reported no specific pattern of cardiomyocyte array in dilated cardiomyopathy (DCM), partially because lack of alignment assessment in a three-dimensional (3D) manner. Here we have established a novel method to evaluate cardiomyocyte alignment in 3D using intravital heart imaging and demonstrated homogeneous alignment in DCM mice. Whilst cardiomyocytes of control mice changed their alignment by every layer in 3D and position twistedly even in a single layer, termed myocyte twist, cardiomyocytes of DCM mice aligned homogeneously both in two-dimensional (2D) and in 3D and lost myocyte twist. Manipulation of cultured cardiomyocyte toward homogeneously aligned increased their contractility, suggesting that homogeneous alignment in DCM mice is due to a sort of alignment remodelling as a way to compensate cardiac dysfunction. Our findings provide the first intravital evidence of cardiomyocyte alignment and will bring new insights into understanding the mechanism of heart failure.

16.
JACC Case Rep ; 3(5): 806-810, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34317630

RESUMO

Coronary artery aneurysm and pseudoaneurysm are rare and mainly result from atherosclerosis. We present a successfully treated case of a giant right coronary artery aneurysm and pseudoaneurysm with a coronary artery fistula, which might have developed after cardiac surgery for a right ventricular tumor 35 years earlier. (Level of Difficulty: Advanced.).

17.
JACC Case Rep ; 3(5): 816-817, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34317632

RESUMO

We report the case of a patient with severely calcified constrictive pericarditis and liver cirrhosis who underwent successful off-pump radical pericardiectomy. The cardiac parameters significantly improved without severe complications. We demonstrate the usefulness of off-pump surgical treatment for constrictive pericarditis with liver cirrhosis. (Level of Difficulty: Intermediate.).

18.
Regen Ther ; 18: 182-190, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34307796

RESUMO

Introduction: Idiopathic dilated cardiomyopathy (DCM) is associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. Mesenchymal stem cells (MSCs) can ameliorate distressed mitochondrial and structural proteins, as well as fibrosis, via the paracrine effect of cytokines. This study aimed to investigate whether the transplantation of adipose tissue-derived MSCs (ADSCs) reverses histological and functional abnormalities in the distressed myocardium of DCM-like hamsters by modulating the expression of adenine nucleotide translocase 1 (ANT-1). Methods: Eighteen weeks after birth, ADSCs were implanted onto the cardiac surface of δ-sarcoglycan (SG)-deficient hamsters or sham surgery was performed. Results: Left ventricular ejection fraction and end-systolic diameter were maintained in ADSC-treated animals for four weeks, ATP concentration was considerably elevated in the cardiomyocytes of these animals, and ANT-1 expression was significantly upregulated as well. The expression of extracellular matrix and myocardial cytoskeletal proteins, such as collagen, SG, and α-dystroglycan, did not differ between groups. However, significant improvements in myosin and Smad4 expression, cardiomyocyte hypertrophy, and capillary density occurred in the ADSC-treated group. Conclusions: We demonstrated that ADSCs might maintain cardiac function in the DCM hamster model by enhancing ATP concentration, as well as mitochondrial transporter and myosin expression, indicating their potential for DCM treatment.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34246489

RESUMO

BACKGROUND: In patients with ischemic mitral regurgitation (MR) undergoing restrictive mitral annuloplasty (RMA), the ratio of left ventricular (LV) end-systolic dimension (LVESD) to mitral valve (MV) ring size (ie, LV-MV ring mismatch) is associated with postoperative recurrent MR. However, the impact of LV-MV ring mismatch on postoperative recurrent MR, LV function recovery, and long-term survival in patients with nonischemic dilated cardiomyopathy (DCM) remains unknown. METHODS: Sixty-six patients with nonischemic DCM (mean LVESD, 62 mm) underwent RMA (mean ring size, 26 mm) between 2003 and 2014. Recurrent MR was defined as MR grade ≥2+ at a 6-month echocardiographic evaluation. RESULTS: At the 6-month follow-up, 23 patients (35%) had developed recurrent MR. In univariable logistic regression analysis, larger LVESD (P = .012) and LVESD/ring size ratio (P = .008) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe MR, only LVESD/ring size ratio (odds ratio, 4.65; 95% confidence interval, 1.04-25.0; P = .048) remained significantly associated with MR recurrence. Receiver operating characteristic curve analysis demonstrated an optimal cutoff value for the LVESD/ring size ratio of 2.42. Patients with an LVESD/ring size ratio >2.42 (n = 30; mismatch) had a lower 5-year cumulative survival rate compared with those with an LVESD/ring size ratio ≤2.42 (n = 36; nonmismatch) (52% vs 71%; P = .045). Postoperatively, LV dimensions were significantly reduced in both groups; however, improvements in LVEF were only modest in the mismatched group (P = .091). CONCLUSIONS: LV-MV ring size mismatch was associated with an increased risk of recurrent MR in our series. This finding may aid the formulation of surgical strategies for patients with nonischemic DCM.

20.
J Heart Lung Transplant ; 40(8): 767-777, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34108109

RESUMO

BACKGROUND: Although induced pluripotent stem (iPS) cell-derived cardiac constructs may have a potential in cardiomyogenesis of a distressed myocardium, obtaining polarity in cardiac constructs, such as via myocyte alignment, may be crucial to achieve a maximum contractile force for better clinical outcomes. We herein hypothesized that transplantation of an aligned cardiac tissue derived from iPS cells has therapeutic effects in a porcine ischemic cardiomyopathy model as a preclinical trial. METHODS: Aligned cardiac tissues were developed by culturing high-purity iPS cell-derived cardiomyocytes in xeno-free conditions and transplanting them into infarct porcine hearts (iPS-CM group, n = 7; control, n = 6). Three months after treatment, therapeutic efficacy was evaluated functionally and histologically. RESULTS: In vitro assessment revealed that the aligned cardiac tissue containing high purity cardiomyocytes contracted homogeneously and had excellent mechanical properties. In the in vivo study, the left ventricular ejection fraction of the iPS-CM group was significantly greater than that of the control group, 3 months after transplantation (37.8% ± 2.3% vs 28.3% ± 2.5%, p < 0.05). Pathologically, attenuated interstitial fibrosis, attenuation of hypertrophied cardiomyocytes, and an increased capillary density were also prominent in the iPS-CM group. A limited amount of engraftment of the transplanted tissue maintaining tissue alignment was observed at 2 weeks after transplantation. CONCLUSIONS: The creation of large-scale functional aligned cardiac tissue was feasible, and the transplantation of the aligned tissue improved cardiac function with angiogenesis and antifibrotic effects in a porcine cardiomyopathy model.

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