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The aim of this study was to review long-term clinical outcomes and valve performance after Epic Supra valve implantation in aortic position. From 2011 to 2022, 44 patients (mean age 75 ± 8 years) underwent surgical aortic valve replacement (SAVR) with an Epic Supra valve at our hospital. Survival, incidence of late complications, and echocardiographic date were retrospectively analyzed. During a mean follow-up period of 6.2 ± 3.5 years, the overall survival rate was 91 ± 4% at 2 and 88 ± 5% at 5 years, while rates of freedom from major adverse cardiovascular and cerebrovascular events (MACCE) were 86 ± 5% and 83 ± 6%, respectively. There was one case of reoperation for prosthetic valve endocarditis at 6 years after the initial surgery. Echocardiographic examinations showed 5-year rates of freedom from severe structural valve deterioration (SVD) and moderate SVD of 100 and 92%, respectively. There was no significant increase in mean pressure gradient or decrease in left ventricular ejection fraction from 1 week after surgery to the late follow-up period. Long-term clinical results and durability of the Epic Supra valve in aortic position were satisfactory., (© 2023. The Japanese Society for Artificial Organs.)

We describe a case in which an axillary Impella 5.0, stuck in an area of calcification in the right subclavian artery, could not be retrieved in the usual manner. However, it was successfully removed using a long 22-Fr sheath and snaring catheter by means of the trans-femoral artery. Device retrieval using the trans-femoral artery snare technique is considered a valid option for removing the Impella device in patients who exhibit this complication., (© 2022. The Japanese Society for Artificial Organs.)

Background: The use of donor hearts with valvular disease has been considered debatable in heart transplantation for many years. However, few reports indicate successful heart transplantation using donor hearts with mitral regurgitation that underwent mitral valve repair on the back bench., Case Presentation: We report two cases of a 38-year-old and a 48-year-old woman with implantable left ventricular assist devices who underwent heart transplantation at our institution. Transthoracic echocardiography of donor hearts just before the explant revealed that each donor heart had preserved cardiac function and significant mitral regurgitation due to mitral posterior leaflet prolapse and annular dilatation, respectively. Bench mitral valve repair was accomplished using triangular resection for one patient and annuloplasty for the other. This was followed by confirmation of excellent mitral leaflet coaptation without residual mitral regurgitation. Transthoracic echocardiography and right heart catheterization performed 6 months after transplantation clarified the favorable cardiac function of each transplanted heart without mitral regurgitation recurrence., Conclusions: Efficient utilization of donor hearts with mitral regurgitation may be acceptable when the cardiac function of donor hearts with mitral regurgitation is preserved and heart transplantation, including bench mitral valve repair, is feasible within an acceptable ischemic time., (© 2023. The Author(s).)

Objective: In patients with ischemic cardiomyopathy, coronary artery bypass grafting ensures better survival than medical therapy. However, the long-term clinical impact of complete revascularization remains unclear. This observational study aimed to evaluate the effects of complete revascularization on long-term survival and left ventricular functional recovery in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting., Methods: We retrospectively reviewed outcomes of 498 patients with ischemic cardiomyopathy who underwent complete (n = 386) or incomplete (n = 112) myocardial revascularization between 1993 and 2015. The baseline characteristics were adjusted using inverse probability of treatment weighting to reduce the impact of treatment bias and potential confounding. The mean follow-up duration was 77.2 ± 42.8 months in survivors., Results: The overall 5-year survival rate (complete revascularization, 72.5% vs incomplete revascularization, 57.9%, P  = .03) and freedom from all-cause death and/or readmission due to heart failure (54.5% vs 40.1%, P  = .007) were significantly greater in patients with complete revascularization than those with incomplete revascularization. After adjustments using inverse probability of treatment weighting, the complete revascularization group demonstrated a lower risk of all-cause death (hazard ratio, 0.61; 95% confidence interval, 0.43-0.86; P  = .005) and composite adverse events (hazard ratio, 0.59; 95% confidence interval, 0.44-0.79; P  < .001) and a greater improvement in the left ventricular ejection fraction 1-year postoperatively (absolute change: 11.0 ± 11.9% vs 8.3 ± 11.4%, interaction effect P  = .05) than the incomplete revascularization group., Conclusions: In patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting, complete revascularization was associated with better long-term outcomes and greater left ventricular functional recovery and should be encouraged whenever possible., (© 2023 The Author(s).)

Thrombus formation is a troublesome and sometimes lethal complication occurring in patients with severe heart failure and supported by a left ventricular assist device (LVAD). Appropriate treatment for pump thrombosis especially in emergency cases with severe pump failure is difficult to choose. Herein, we present important findings of a case of unexpected LVAD pump thrombosis that rapidly developed into serious pump failure and circulatory arrest due to total obstruction of the LVAD inflow tract by a huge thrombus., (© 2022. The Japanese Society for Artificial Organs.)

Objectives: The study objectives were to determine the incidence, predictors, and clinical impact of ventricular arrhythmias after coronary artery bypass grafting and to evaluate the impact of implantable cardioverter defibrillators on the survival of patients with ventricular arrhythmias., Methods: We enrolled 498 patients with a left ventricular ejection fraction of 40% or less who underwent coronary artery bypass grafting between 1993 and 2015. Clinical follow-up was completed in 94.0% of patients, with a median follow-up of 58.4 months., Results: Overall, 212 patients (43%) died, mainly of heart failure (n = 54, 10.8%) or sudden cardiac death (n = 40, 8.0%). The sudden cardiac death rate was highest during the first 6 months, with a monthly rate of 0.37%. Overall, 99 patients (20%) developed postoperative ventricular arrhythmias, and implantable cardioverter defibrillator was implanted in 55 patients. Previous ventricular arrhythmias (hazard ratio, 3.22; 95% confidence interval, 1.98-5.24; P  < .001), left ventricular end-systolic dimension (hazard ratio, 1.07; 95% confidence interval, 1.04-1.10; P  < .001), and myocardial infarction in the left anterior descending artery territory (hazard ratio, 1.73; 95% confidence interval, 1.10-2.73; P  = .02) were independent predictors of postoperative ventricular arrhythmias. Notably, the 5-year survival of patients with ventricular arrhythmias who received an implantable cardioverter defibrillator was significantly higher than that of patients with ventricular arrhythmias who did not receive it (76.1% vs 22.7%, P  < .001) and was comparable to that of patients without ventricular arrhythmias (76.1% vs 73.6%, P  = .98)., Conclusions: Sudden cardiac death affects a significant proportion of patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting, most frequently within 6 months postoperatively. To prevent sudden cardiac death, earlier implantable cardioverter defibrillator implantation should be indicated for high-risk patients with scars in the left anterior descending artery territory and excessive left ventricular remodeling., (Copyright © 2023 Published by Elsevier Inc.)

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 a left ventricular 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 postoperative recurrent MR (moderate or severe) were excluded. Finally, 146 patients (aged 68 [63-75] years) whose MR was well controlled over time were included., Results: A total of 61 deaths or 27 readmissions for heart failure were observed in 76 patients (52%). Among hospital survivors, age (adjusted hazard ratio, 1.05; P = .001) and estimated glomerular filtration rate (adjusted hazard ratio, 0.61; P = .001) were identified as independent predictors of long-term mortality or readmission for heart failure. The degree of postoperative left ventricular function recovery 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 < .05 for all)., Conclusions: Approximately 50% of patients died or were hospitalized for heart failure even in the absence of recurrent MR during the 5-year follow-up, a finding indicating that durable mitral repair does not always lead to favorable clinical outcomes. The adverse events may have been related to volume overload secondary to impaired renal function and less favorable pulmonary hemodynamics., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Women with implantable left-ventricular assist devices (LVADs) experience gynecological bleeding (GYN-bleeding). However, a few studies have investigated female-specific problems. Therefore, this study aimed to identify the risk factors for adverse GYN-bleeding after LVAD implantation. We retrospectively analyzed 59 women (mean age: 41 ± 15 years) with long-term implantable LVAD support (≥ 6 months) at our institution between 2005 and 2018. The history of GYN-bleeding before implantation was defined as abnormal utero-ovarian bleeding, excessive menstruation, uterine fibroids, and endometrial lesions. GYN-bleeding after implantation was defined as a requirement of emergency outpatient visits and/or hospitalization, blood transfusions, hormonal therapy, and/or surgery. Additionally, risk factors for GYN-bleeding were identified using the Cox regression model. Twenty-four GYN-bleeding cases were seen in 15 patients (two times: five patients, three times: two patients, 0.18 events per patient-year). The 1- and 2-year GYN-bleeding-free rates were 84% and 73%, respectively. Twelve patients (17 events) required RBC ≥ 4 units, and five patients (7 events) required FFP ≥ 4 units. Seven patients required pseudomenopausal treatment after blood transfusion, and four patients required surgical treatment. Fifteen patients with GYN-bleeding after implantation were significantly younger than the remaining 44 patients without GYN-bleeding (34 ± 12 years vs. 43 ± 16 years, P = 0.02). Multivariable risk analysis showed a history of GYN-bleeding before implantation was a significant risk factor (hazard ratio 3.7 [1.2-10.6], P = 0.004). Patients with a history of GYN-bleeding before LVAD implantation have a high risk of developing GYN-bleeding after implantation. We should identify the high-risk population and prepare for the management of GYN-bleeding., (© 2021. The Japanese Society for Artificial Organs.)

Objectives: Although adipose-derived stem cells (ADSCs) have shown promise in cardiac regeneration, stable engraftment is still challenging. Acellular bioengineered cardiac patches have shown promise in positively altering ventricular remodeling in ischemic cardiomyopathy. We hypothesized that combining an ADSC sheet approach with a bioengineered patch would enhance ADSC engraftment and positively promote cardiac function compared with either therapy alone in a rat ischemic cardiomyopathy model., Methods: Cardiac patches were generated from poly(ester carbonate urethane) urea and porcine decellularized cardiac extracellular matrix. ADSCs constitutively expressing green fluorescent protein were established from F344 rats and transplanted as a cell sheet over the left ventricle 3 days after left anterior descending artery ligation with or without an overlying cardiac patch. Cardiac function was serially evaluated using echocardiography for 8 weeks, comparing groups with combined cells and patch (group C, n = 9), ADSCs alone (group A, n = 7), patch alone (group P, n = 6) or sham groups (n = 7)., Results: Much greater numbers of ADSCs survived in the C versus A groups (P < .01). At 8 weeks posttransplant, the percentage fibrotic area was lower (P < .01) in groups C and P compared with the other groups and vasculature in the peri-infarct zone was greater in group C versus other groups (P < .01), and hepatocyte growth factor expression was higher in group C than in other groups (P < .05). Left ventricular ejection fraction was higher in group C versus other groups., Conclusions: A biodegradable cardiac patch enhanced ADSC engraftment, which was associated with greater cardiac function and neovascularization in the peri-infarct zone following subacute myocardial infarction., (Published by Elsevier Inc.)

In this article, we analyzed 114 adult heart transplantation( HTx) cases from 1999 to 2021. Of these cases, 94% of patients underwent left ventricular assist device ( LVAD) implantation before HTx. The mean period of LVAD support was 3.0 ±1.2 years. Thirty-day mortality was 0.8% and the 10-year survival rate was 89% after HTx. Preoperative and postoperative renal function was the prognostic factors. Long LVAD support was not associated with the long-term survival after HTx.

Ventricular septal rupture after acute myocardial infarction is a fatal complication with a very high in-hospital mortality. Herein, we describe a new repair technique using a first patch for exclusion of the infarcted myocardium and a second sutureless patch for rupture site closure with a novel tissue adhesive (Hydrofit, Terumo, Tokyo, Japan). Follow-up of over 2 years revealed a good clinical course and no residual interventricular shunt on echocardiography. This modified infarct exclusion technique with a second sutureless patch has a benefit of avoiding stitches to the fragile infarcted myocardium and might be effective in preventing interventricular shunt recurrence after ventricular septal rupture., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Consensus regarding an optimal atrial fibrillation (AF) ablation lesion set concomitant with aortic valve replacement (AVR) and/or coronary artery bypass grafting (CABG) has not been established., Methods: We enrolled 125 consecutive patients (89 men; 70 ± 8 years old) with persistent AF who underwent radiofrequency-based pulmonary vein isolation (PVI) (PVI group, n = 53) or a Cox-Maze procedure (Maze group, n = 72) with AVR and/or CABG. To reduce the impact of treatment bias and potential confounding in the direct comparisons between patients who underwent Cox-Maze with and those who underwent PVI, we established weighted Cox proportional-hazards regression models with inverse probability of treatment weighting. Mean follow-up was 63 ± 34 months (maximum, 154 months)., Results: There was 1 in-hospital death in each group. Patients who underwent Cox-Maze showed a higher freedom from AF at all follow-up examinations. After the operation, there were 32 deaths, 13 thromboembolisms, 8 hemorrhagic events, and 22 heart failure readmissions. The Maze group had higher rates for 5-year survival (88% vs 64%, P = .013) and freedom from composite events (74% vs 42%, P < .001). After adjustment with inverse probability of treatment weighting, the Cox-Maze procedure still showed a lower risk of overall mortality (adjusted hazard ratio, 0.38; 95% confidence interval, 0.21-0.66; P = .001) and composite adverse events (adjusted hazard ratio, 0.52; 95% confidence interval, 0.35-0.76; P = .001)., Conclusions: In patients with persistent AF indicated for nonmitral valve surgery, a concomitant Cox-Maze procedure resulted in superior AF- and event-free survival compared with PVI, without increased risk of early mortality. These findings may assist decision making for surgical management of persistent AF concomitant with AVR and/or CABG., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: In patients with severe left ventricular (LV) dysfunction requiring coronary artery bypass grafting (CABG), the association between diabetic status and outcomes after surgery, as well as with survival benefit following bilateral internal thoracic artery (ITA) grafting, remain largely unknown., Methods and results: Patients (n=188; mean [±SD] age 67±9 years) with LV ejection fraction ≤40% who underwent isolated initial CABG were classified into non-diabetic (n=64), non-insulin-dependent diabetic (NIDM; n=74), and insulin-dependent diabetic (IDM; n=50) groups. During follow-up (mean [±SD] 68±47 months), the 5-year survival rate was 84% and 65% among non-diabetic and diabetic patients, respectively (P=0.034). After adjusting for all covariates, both NIDM and IDM were associated with increased mortality, with hazard ratios (HRs) of 1.9 (95% confidence interval [CI] 1.0-3.7; P=0.049) and 2.4 (95% CI 1.2-4.8; P=0.016), respectively. Among non-diabetic patients, there was no difference in the 5-year survival rate between single and bilateral ITA grafting (86% vs. 80%, respectively; P=0.95), whereas bilateral ITA grafting increased survival among diabetic patients (57% vs. 81%; P=0.004). Multivariate analysis revealed that bilateral ITA was significantly associated with a decreased risk of mortality (HR 0.3; 95% CI 0.1-0.8; P=0.024)., Conclusions: NIDM and IDM were significantly associated with worse long-term clinical outcome after CABG for severe LV dysfunction. Bilateral ITA grafting has the potential to improve survival in diabetic patients with severe LV dysfunction.

Objectives: This retrospective study aimed to clarify the incidence, determinants and clinical impact of left ventricular (LV) function non-recovery after coronary artery bypass grafting (CABG) in patients with ischaemic cardiomyopathy., Methods: A total of 490 patients with ischaemic cardiomyopathy (LV ejection fraction ≤ 40%) undergoing CABG were analysed. Follow-up echocardiography was performed at 1 month, 1 year, and annually thereafter. LV function recovery was defined as ejection fraction (EF) ≥40% at least once during follow-up. LV function non-recovery was defined as EF <40% at any follow-up. The primary and secondary end points were changes in LV function and all-cause mortality, respectively. Clinical follow-up was completed in 461 patients (94.1%; mean follow-up: 64.5 ± 45.5 months)., Results: During follow-up, echocardiographic assessments were performed 1863 times (mean, 3.8 ± 2.4), and 193 patients (39.4%) exhibiting LV function non-recovery were identified. Overall survival was significantly higher in the recovery group (53.9%) than in the non-recovery group (31.4%) at 10 years (P < 0.001). Independent predictors of LV function non-recovery were preoperative LV end-systolic diameter [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04-1.10; P < 0.001] and bilateral internal thoracic artery grafting (OR 0.61, 95% CI 0.39-0.95; P = 0.028). In a multivariable Cox proportional hazards model, LV function non-recovery was significantly associated with all-cause mortality (hazard ratio 2.14, 95% CI 1.60-2.86; P < 0.001)., Conclusions: Almost 40% of patients with ischaemic cardiomyopathy undergoing CABG did not achieve LV function recovery and were associated with poor prognosis. To achieve LV function recovery, CABG with bilateral internal thoracic artery may be recommended before excessive LV remodelling occurs., Clinical Trial Registration Number: Institutional review board of Osaka University Hospital, number 16105., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: We investigated whether or not a history of multiple percutaneous coronary interventions (PCIs) is associated with clinical outcomes after surgery for ischemic mitral regurgitation., Methods: A total of 309 patients with chronic ischemic mitral regurgitation and left ventricular ejection fraction ≤40% who underwent restrictive mitral annuloplasty were classified as follows: patients with no or 1 previous PCI (nonmultiple PCI group [n = 211]) and patients with 2 or more previous PCIs (multiple PCIs group [n = 98]). Mean follow-up duration was 53 ± 40 months., Results: Before surgery, there were no intergroup differences in patient demographic characteristics except for lower estimated glomerular filtration rate in patients with multiple PCIs. These patients underwent concomitant coronary artery bypass grafting less frequently with a lower number of distal anastomoses ( P  < .05 for both). The 30-day mortality was 3.3% and 2.0% in the nonmultiple and multiple PCIs group, respectively ( P  = .72). During follow-up, there were 157 deaths. Patients with multiple PCIs showed lower 5-year survival rate (44% vs 64%; P  = .002). After adjustments with inverse-probability-of-treatment weighting, multiple PCIs history was an independent risk factor for mortality (adjusted hazard ratio, 1.4; 95% confidential interval, 1.1-1.7; P  = .002). Patients with multiple PCIs showed less improvement in left ventricular ejection fraction (interaction effect P  < .001)., Conclusions: In patients with ischemic mitral regurgitation, a history of previous multiple PCIs was associated with increased risk of long-term postoperative mortality, with less improvement in left ventricular ejection fraction., (© 2021 The Authors.)

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·m 2 ·beat [22.7-35.5 g·m 2 ·beat] to 32.8 g·m 2 ·beat [28-38.5 g·m 2 ·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.

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. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background: This study retrospectively examined the association between elevated trans-pulmonary gradient (TPG), which reflects pre-capillary contribution to pulmonary hypertension (PH), and postoperative pulmonary hemodynamics and outcomes following restrictive mitral annuloplasty (RMA) in patients with pre-existing PH., Methods: Pre- and postoperative (1 month) cardiac catheterization was performed in 64 patients with severely impaired left ventricular function (i.e., ejection fraction ≤40%) and pre-existing PH (mean pulmonary artery pressure (PAP) ≥25 mmHg) who underwent RMA. Patients were segregated into two groups: low TPG (≤12 mmHg) and elevated TPG (>12 mmHg). The mean follow-up period was 54±27 months. The primary outcome seen was a change in pulmonary hemodynamics after RMA; secondary outcomes were composite adverse events, including all-cause mortality and readmission for heart failure., Results: Compared to the low TPG group, patients in the elevated TPG group were more likely to show a postoperative mean PAP of ≥25 mmHg (84% vs. 38%), TPG of >12 mmHg (79% vs. 11%), and pulmonary vascular resistance of ≥240 dynes/sec/cm -5 (84% vs. 6.7%) (all P<0.001), although both groups showed comparable degrees of mitral regurgitation improvement. Serial echocardiography demonstrated that Doppler-derived systolic PAP, which once decreased in both groups, remained stable in the low group while steadily increasing in the elevated group (group effect P<0.001). Patients with elevated TPG had lower freedom from composite adverse events (5-year, 20% vs. 70%, P=0.003). After adjusting for baseline covariates, the elevated TPG was independently associated with increased risk of adverse events (adjusted hazard ratio 2.9, 95% CI: 1.2-6.9, P=0.017)., Conclusions: Elevated TPG negatively affects postoperative pulmonary hemodynamics and late outcomes in patients with advanced cardiomyopathy and pre-existing PH who have undergone RMA. These findings suggest that the assessment of TPG should be included in post-RMA risk stratification., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2898). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Background: In this study, we evaluated the prevalence of tricuspid regurgitation (TR) worsening in patients with left ventricular assist devices (LVADs) and its impact on late right ventricular (RV) failure., Methods: We enrolled 147 patients of the 184 patients who underwent continuous-flow LVAD implantations from 2005 to March 2018. The prevalence of postoperative TR worsening and late RV failure were retrospectively evaluated., Results: Concomitant tricuspid annuloplasty (TAP) was performed in 28 of 41 patients (68%) with preoperative TR greater than or equal to moderate (TR group) and in 23 of 106 patients (22%) with preoperative TR less than or equal to mild (non-TR group). Regarding the TR-free rates, despite receiving or not receiving concomitant TAP, there was no significant difference between the 2 groups (TR group: p = 0.37; non-TR group: p = 0.42). Of the 9 patients with postoperative TR greater than or equal to moderate, late RV failure developed in 3 patients, with TR worsening after RV failure in each case. During follow-up, 16 patients (11%) had late RV failure. As for the late RV failure-free rates, despite receiving or not receiving concomitant TAP, there was no significant difference between the 2 groups (TR group: p = 0.37; non-TR group: p = 0.96)., Conclusions: TR prognosis was preferable regardless of a patient receiving concomitant TAP; however, the presence of postoperative TR seemed to unrelated to late RV failure. Prophylactic TAP might not be necessary to prevent late RV failure.

We evaluated the cardiac function recovery following skeletal myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.6%) patients were defined as responders, and the average increase in left ventricular ejection fraction was 4.9%. The responders achieved greater improvement degrees in left ventricular and hemodynamic function parameters, and they presented improved exercise capacity. During the follow-up period (56 ± 28 months), there were four deaths and the overall 5-year survival rate was 95%. Although the responders showed higher freedom from mortality and/or heart failure admission (5-year, 81% versus 0%; p = 0.0002), both groups presented an excellent 5-year survival rate (5-year, 93% versus 100%; p = 0.297) that was higher than that predicted using the Seattle Heart Failure Model. The stepwise logistic regression analysis showed that the preoperative estimated glomerular filtration rate and the left ventricular end-systolic volume index were independently associated with the recovery progress. Approximately 70% of patients with "no-option" ischemic cardiomyopathy responded well to the cell-sheet transplantation. Preoperative renal and left ventricular function might predict the patients' response to this treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cardiogenic shock due to acute severe mitral regurgitation is characterized by multiple organ failure and acute pulmonary edema, leading to a high risk of mortality. Methods and Results: We report on a patient with acute, severe mitral regurgitation complicated by cardiogenic shock, refractory to both inotrope treatment and intra-aortic balloon pump support. The patient was successfully bridged to surgery with an Impella CP, a percutaneous left ventricular assist device. Conclusions: Mechanical support using an Impella CP can stabilize hemodynamics and may be used as a bridge to elective surgery for patients with mitral regurgitation with cardiogenic shock., Competing Interests: Y. Sawa is a member of Circulation Reports’ Editorial Board., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Avoiding immune rejection after allogeneic induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) transplantation is a concern. However, mesenchymal stem cells (MSCs) can suppress immune rejection. To determine whether MSC co-transplantation can reduce immune rejection after allogeneic iPSC-CM transplantation, the latter cell type, harbouring a luciferase transgene, was subcutaneously transplanted alone or together with syngeneic MSCs into BALB/c mice. Bioluminescence imaging revealed that MSC co-transplantation significantly improved graft survival (day 7: iPSC-CMs alone 34 ± 5%; iPSC-CMs with MSCs, 61 ± 7%; P = 0.008). MSC co-transplantation increased CD4 + CD25 + FOXP3 + regulatory T cell numbers, apoptotic CD8-positive T cells, and IL-10 and TGF-beta expression at the implantation site. Analysis using a regulatory T cell depletion model indicated that enhanced regulatory T cell populations in the iPSC-CM with MSC group partially contributed to the extended iPSC-CM survival. Further, MSCs affected activated lymphocytes directly through cell-cell contact, which reduced the CD8/CD4 ratio, the proportion of Th1-positive cells among CD4-positive cells, and the secretion of several inflammation-related cytokines. Syngeneic MSC co-transplantation might thus control allogeneic iPSC-CM rejection by mediating immune tolerance via regulatory T cells and cell-cell contact with activated lymphocytes; this approach has promise for cardiomyogenesis-based therapy using allogeneic iPSC-CMs for severe heart failure.

The indications for mitral valve surgery in patients with advanced nonischemic dilated cardiomyopathy and functional mitral regurgitation are still unclear. We reviewed our experience of mitral valve surgery in such patients and explored factors that were predictive of outcomes. Fifty-three consecutive patients with nonischemic dilated cardiomyopathy and an ejection fraction <35% who underwent mitral valve surgery were reviewed. Thirty five patients (66%) suffered all-cause death or underwent admission for heart failure or left ventricular assist device implantation after mitral valve surgery during follow-up (37 ± 27 months); freedom from these events at 3 years was 45%. Mitral valve surgery significantly reduced left ventricular volume (P < 0.01) and pulmonary vascular resistance (P < 0.01) in survivors. New York Heart Association functional class also improved significantly (P < 0.01) at 1 year after surgery. By multivariate analysis, preoperative left ventricular stroke work index (P < 0.04) was the sole significant predictor of composite outcomes including all-cause mortality, admission for heart failure or left ventricular assist device implantation after mitral valve surgery, with a cut-off value of 25.9 g-m/m 2 /beat. A higher tethering height (≥11 mm, P < 0.01) was a significant predictive factor for mitral regurgitation recurrence (P = 0.02). Mitral valve surgery for significant functional mitral regurgitation associated with nonischemic cardiomyopathy is still challenging. However, thorough hemodynamic investigations prior to surgery could provide useful indications regarding mitral valve surgery in these patients, contributing to an improvement in their clinical outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although allogeneic-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) exhibit potential in cardiomyogenesis for heart failure, whether major histocompatibility complex (MHC)-matched allogenic iPSC implantation (MMAI) minimizes immune rejection for cell survival or functional recovery remains unknown. We herein explored whether MMAI with an iPSC-CM sheet is stable for a longer period and therapeutically more effective than MHC-mismatched AI in a primate ischemic cardiomyopathy model., Methods: Green fluorescent protein-transfected iPSC-CM sheets, derived from cynomolgus macaques with homozygous MHC haplotypes ''HT1,'' were transplanted on the left ventricle, generated by ligating the left anterior descending artery for 2 weeks in an ischemic model with or without heterozygous HT1 as MMAI and MHC-mismatched AI. Sham models were made by opening the chest at 14 days after left anterior descending ligation without any treatment., Results: Stereomicroscopy revealed that at 4 months after transplantation, green fluorescent protein intensity was higher in the MMAI group than in the MHC-mismatched AI group and the sham group. Immunohistochemistry staining revealed that host immune reaction with CD3-positive cells was stronger in MHC-mismatched AI than in MMAI at 3 months. Cardiac function improved both in MMAI and MHC-mismatched AI at 1 month after transplantation and was preserved until 6 months, whereas in the sham group, functional deterioration progressed over time., Conclusions: Although MHC-homo-iPSCs are preferred to avoid immune rejection, MHC-mismatched iPSC-CMs can also induce comparable cardiac functional recovery at late follow-up, suggesting that MHC-mismatched iPSC-based cardiac regenerative therapy with immunosuppressants is a feasible option for treating heart failure in clinical settings.

Allogeneic transplantation of induced pluripotent stem cell (iPSC)-derived cardiomyocytes is apromising treatment for cardiac diseases, although immune rejection by the recipient poses a concern. In this study, we aimed to investigate whether concomitant transplantation of vasculogenically conditioned peripheral blood mononuclear cells, which are otherwise immunosuppressive, may enhance graft survival. Luciferase-transduced, iPSC-derived cardiomyocytes from C57BL/6 mice were transplanted to the dorsal subcutaneous space of syngeneic C57BL/6 mice (n = 19), allogeneic Balb/c mice treated with (n = 20) or without (n = 20) immunosuppressants, and those injected with vasculogenically conditioned peripheral blood mononuclear cells (n = 20). Although graft survival, assessed by bioluminescence, was comparable among the groups initially, it improved significantly at days 7 and 10 in allogeneic transplanted mice treated with vasculogenically conditioned peripheral blood mononuclear cells than in others (P < 0.01). Our results proved that cell-based immunosuppression may boost clinical outcomes from allogeneic cell therapy., Competing Interests: The authors have declared that no competing interests exist.

In this study, we proposed that the functionality or phenotype of differentiated cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) might be modified by co-culture with mesenchymal stem cells (MSCs), resulting in an improved therapeutic potential for failing myocardial tissues. Structural, motility, electrophysiological, and metabolic analyses revealed that iPSC-CMs co-cultured with MSCs displayed aligned myofibrils with A-, H-, and I-bands that could contract and relax quickly, indicating the promotion of differentiation and the establishment of the iPSC-CM structural framework, and showed clear gap junctions and an electric pacing of >2 Hz, indicating enhanced cell-cell interactions. In addition, soluble factors excreted by MSCs, including several cytokines and exosomes, enhanced cardiomyocyte-specific marker production, produced more energy under normal and stressed conditions, and reduced reactive oxygen species production by iPSC-CMs under stressed condition. Notably, gene ontology and pathway analysis revealed that microRNAs and proteins in the exosomes impacted the functionality and maturation of iPSC-CMs. Furthermore, cell sheets consisting of a mixture of iPSC-CMs and MSCs showed longer survival and enhanced therapeutic effects compared with those consisting of iPSC-CMs alone. This may lead to a new type of iPSC-based cardiomyogenesis therapy for patients with heart failure., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The degree or nature of functional mitral regurgitation (MR) is not necessarily correlated with the size or function of the left ventricle (LV). We hypothesized that the anatomical structure of the mitral valve (MV) complex might play a role in functional MR in ischemic or nonischemic dilated cardiomyopathy (DCM).The structure of the LV and MV complex in DCM patients (n = 29) was assessed using electrocardiogram-gated 320-slice computed tomography and was compared with that in healthy patients (n = 12). Twenty-five DCM patients with mild or low MR (DCM-lowMR) had markedly greater length, diameter, and sphericity index of the LV and a larger tenting area than the controls. The distance between the papillary muscle (PM) tip and the mitral annular plane was not different between DCM-lowMR and normal hearts despite the greater LV length observed in DCM-lowMR. Furthermore, DCM-lowMR had markedly longer chordae tendineae (DCM-lowMR: 24 [20-26] mm; controls: 14 [13-16] mm; P < 0.01) and larger anterior leaflets (DCM-lowMR: 30 [27-31] mm; controls: 22 [20-24] mm; P < 0.01), thus suggesting the adaptive remodeling of the MV complex. Four DCM patients with moderate-severe MR had unbalanced remodeling, such as excessive LV dilatation, short anterior mitral leaflets, and short chordae tendineae.The development of functional MR might be associated with the remodeling of LV and MV components, such as the PMs, chordae tendineae, or anterior MV leaflets. Detailed anatomical assessments of the LV and MV complex would contribute to the adequate staging of ischemic or nonischemic DCM.

Background: Blood stream infection is thought to increase the risk of hemorrhagic stroke, a major adverse event with devastating outcome, in patients with continuous-flow left ventricular assist devices (LVADs). We analyzed the risk factors of hemorrhagic stroke in LVAD patients, as well as the time relationship between systemic bacteremia and hemorrhagic stroke.Methods and Results:We evaluated the incidence of systemic bacteremia and stroke in 164 patients who underwent continuous-flow LVAD implantation between 2005 and 2016. At 1 and 2 years after implantation, the incidence of bacteremia was 29% and 36%, and the incidence of hemorrhagic stroke was 22% and 22% in patients without bacteremia, and 32% and 44% in those with bacteremia, respectively (P=0.035). This higher prevalence of hemorrhagic stroke in patients with bacteremia was notable particularly in the chronic phase (>90 days after implantation). Multivariate analysis revealed that bacteremia was an independent risk factor of hemorrhagic stroke in the chronic phase [hazard ratio, 2.36 (1.02-5.62); P=0.044]. The hazard rate was the highest immediately after the onset of bacteremia, and the risk steadily declined by 90 days after the last episode of bacteremia and flattened thereafter., Conclusions: Bacteremia was an independent risk factor of hemorrhagic stroke in patients in the chronic phase, with the highest risk seen in the early phase following an episode of bacteremia.

Background: Although implantation of a left ventricular assist device (LVAD) induces reverse remodeling of the left ventricle in end-stage nonischemic dilated cardiomyopathy (DCM), the underlying mechanism is not fully understood. It has been shown that epigenetic modification, such as methylation or acetylation of the histone, is one of the most important upstream signals in cardiac failure. This study hypothesized that histone profiles may be modified by LVAD implantation for end-stage nonischemic DCM, in association with reverse left ventricular remodeling., Methods: Hemodynamic changes associated with histone modification profiles in the left ventricle were comprehensively assessed in 14 patients with a diagnosis of end-stage nonischemic DCM. These patients underwent LVAD implantation and subsequent cardiac transplantation in our institution (Osaka University Hospital, Osaka, Japan). Samples of normal left ventricle from 3 different people were used as a control., Results: After LVAD support for 2.5 ± 1.2 years, the study cohort showed a significant reverse remodeling of left ventricular function associated with histopathologic changes in the left ventricle, such as reduction of myocyte size. Although the left ventricle of the cohort histologically expressed less 3 histone methylation-related molecules (eg, H3 lysine 4 trimethylation [H3K4me3], H3 lysine 9 dimethylation [H3K9me2], and H3 lysine 9 trimethylation [H3K9me3]) compared with normal left ventricle, LVAD support reversed expression of these molecules, associated with up-regulation of H3 lysine 9 [H3K9] methyltransferase and suppressor of variegation 3-9 homologue 1 [SUV39H1] and with down-regulation of H3K9 demethylase and jumonji domains [JMJDs] in the LVAD-supported left ventricle. Moreover, expression of atrial natriuretic peptide and brain natriuretic peptide (ANP and BNP) was negatively correlated with that of H3K9me2 and H3K9me3., Conclusions: The epigenetic state of cardiac myocytes (eg, as histone methylation) was substantially modulated in end-stage nonischemic DCM. LVAD support partially reversed the epigenetic state and its upstream signals, in association with pathologic and functional reverse remodeling., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery bypass grafting (CABG) reduces functional mitral regurgitation (MR) associated with ischemic heart disease, although the predictive factors or mechanisms of reversibility of functional MR after CABG are not fully understood.We investigated whether mitral valve structure is associated with the outcome of functional MR after CABG.Methods and Results:From a consecutive series of 98 patients with mild-moderate functional MR preoperatively who underwent isolated CABG, we enrolled 66 patients who were followed up for >1 year postoperatively using echocardiography. The degree of MR was reduced in 34 patients (52%) postoperatively, in association with a lower rate of in-hospital treatment for cardiac failure in the long term, compared with the 32 patients (48%) with residual MR postoperatively. The patients with reduced MR postoperatively had longer estimated coaptation length and more anteriorly or centrally directed MR jets than those without reduced MR. On statistical analysis, the addition of estimated coaptation length and jet direction to the reported predictors (ejection fraction, left ventricular end-diastolic dimension, and tenting height) more accurately predicted changes in post-CABG MR than the reported 3 factors alone., Conclusions: Residual MR was associated with the emergence of congestive heart failure in the long term after CABG. A specific mitral valve structure, such as large mitral leaflet size or predominant tethering of the posterior leaflet, was a predictive factor for the reversibility of post-CABG functional MR.

Objectives: Although right ventricular failure (RVF) is a major concern after left ventricular assist device (LVAD) implantation, methodologies to evaluate RV function remain limited. Liver stiffness (LS), which is closely related to right-sided filling pressure and may indicate RVF severity, could be non-invasively and repeatedly assessed using transient elastography. Here we investigated the suitability of LS as a parameter of RV function in pre- and post-LVAD periods., Methods: The study included 55 patients with LVAD implantation as a bridge to transplantation between 2011 and 2015 whose LS was assessed using transient elastography., Results: Seventeen patients presented with RVF, defined as requiring inotropic support for ≥30 days, nitric oxygen inhalation for ≥5 days, and/or mechanical RV support following LVAD implantation. Survival of patients with RVF was significantly worse compared with that of patients without RVF. Multivariate logistic regression analysis identified preoperative LS, LV diastolic dimension, RV stroke work index, and dilated phase of hypertrophic cardiomyopathy aetiology as significant risk factors; the combination of these parameters could improve predictive power of post-LVAD RVF with areas under the curve of 0.89. Furthermore, LS was significantly decreased by LV unloading and significantly correlated with right-sided filling pressure., Conclusions: In addition to dilated hypertrophic cardiomyopathy aetiology, reduced RV stroke work index and small LV dimension, we demonstrated that non-invasively measured LS was a predictor of post-LVAD RVF and can be used as a parameter for the evaluation and optimization of RV function in the perioperative period., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Allogeneic transplantation (Tx) of induced pluripotent stem cells (iPSCs) is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET) imaging targets translocator protein (TSPO), which is highly expressed on mitochondrial membrane, especially in activated macrophage. N,N-diethyl-2-[4-(2-fluoroethoxy) phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (DPA-714) is known as a TSPO ligand used in clinical settings. We herein hypothesized that immune rejection of the transplanted iPSC-derived cardiomyocytes (iPSC-CMs) of allogeneic origin may be quantitated using 18F-DPA-714-PET imaging study. iPSC-CM cell-sheets of C57BL/6 mice origin were transplanted on the surface of the left ventricle (LV) of C57BL/6 mice as a syngeneic cell-transplant model (syngeneic Tx group), or Balb/c mice as an allogeneic model (allogeneic Tx group). 18F-DPA-714-PET was used to determine the uptake ratio, calculated as the maximum standardized uptake value in the anterior and septal wall of the LV. The uptake ratio was significantly higher in the allogeneic Tx group than in the syngeneic group or the sham group at days 7 and day 10 after the cell transplantation. In addition, the immunochemistry showed significant presence of CD68 and CD3-positive cells at day 7 and 10 in the transplanted graft of the allogeneic Tx group. The expression of TSPO, CD68, IL-1 beta, and MCP-1 was significantly higher in the allogeneic Tx group than in the syngeneic Tx and the sham groups at day 7. The 18F-DPA-714-PET imaging study enabled quantitative visualization of the macrophages-mediated immune rejection of the allogeneic iPSC-cardiac. This imaging tool may enable the understanding and monitoring host-immune response of the host, allogeneic cell transplantation therapy., Competing Interests: The authors have declared that no competing interests exist.

Induced pluripotent stem cells (iPSCs) can serve as a source of cardiomyocytes (CMs) to treat end-stage heart failure; however, transplantation of genetically dissimilar iPSCs even within species (allogeneic) can induce immune rejection. We hypothesized that this might be limited by matching the major histocompatibility complex (MHC) antigens between the donor and the recipient. We therefore transplanted fluorescence-labeled (GFP) iPSC-CMs donated from a macaque with homozygous MHC haplotypes into the subcutaneous tissue and hearts of macaques having heterozygous MHC haplotypes (MHC-matched; group I) or without identical MHC alleles (group II) in conjunction with immune suppression. Group I displayed a higher GFP intensity and less immune-cell infiltration in the graft than group II. However, MHC-matched transplantation with single or no immune-suppressive drugs still induced a substantial host immune response to the graft. Thus, the immunogenicity of allogeneic iPSC-CMs was reduced by MHC-matched transplantation although a requirement for appropriate immune suppression was retained for successful engraftment., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic, and time courses, as assessed by imaging tools including (18)F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells, and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.

Background: It is well-documented that persistent myocardial hypertrophy in patients with aortic stenosis is related to suboptimal postoperative outcomes after aortic valve replacement. Although diabetes is known to potentially exacerbate myocardial hypertrophy, it has yet to be examined if it affects postoperative left ventricular mass regression (LVMR)., Methods: A single-centre, retrospective analysis was performed on 183 consecutive patients who underwent either surgical or transcatheter aortic valve replacement between 2010 and May 2013. Patient demographics, postoperative outcomes and echocardiographic data were obtained preoperatively and a year after surgery., Results: There were 42 diabetic and 141 non-diabetic patients. Preoperative characteristics of diabetic patients were statistically similar to those of non-diabetic patients, except for higher prevalence of hyperlipidaemia (p <0.001) and history of cerebrovascular disorder (p=0.046) in diabetic patients. Median value of postoperative LVMR of all patients was -36.5 g/m(2), and was significantly greater in the non-diabetics compared to the diabetics (-39.1 vs. -22.2 g/m(2), p=0.008). Univariate and multivariate analyses were performed on preoperative variables, and stepwise multiple regression analysis demonstrated that diabetes (standardised partial regression coefficient (SPRC)=-0.187, p=0.018), female gender (SPRC=0.245, p=0.026) and age (SPRC=0.203, p=0.018) were associated with poor postoperative LVMR., Conclusions: Patients with diabetes showed suboptimal postoperative LVMR, and the disease was a prognostic factor that was associated with poor LVMR. These findings suggest that diabetes may predispose the particular group of patients to worse postoperative outcomes., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Unlabelled: Cell-surface glycans vary widely, depending on cell properties. Previously, we reported that the pattern of N-glycan expression on murine induced pluripotent stem cells (iPSCs) changed toward that of the cardiac tissue during cardiomyogenic differentiation. In this study, N-glycans were isolated from human iPSCs, iPSC-derived cardiomyocytes (iPSC-CMs), and human cardiomyocytes (hCMCs). Their structures were analyzed by a mapping technique based on high-performance liquid chromatography elution positions and matrix-assisted laser desorption/ionization time-of-flight mass-spectrometric data. Of 52 isolated N-glycans, the structures of 38 were clearly identified. In addition, 11 structures were partially identified because the binding style and fucose binding site at the nonreduced terminal could not be identified. Quantitation of each type of N-glycan, based on the terminal glycosylation process, revealed that the exposed N-acetylglucosamine (GlcNAc) and the nonreduced terminal fucose types decreased, whereas the exposed galactose or the α2-3 NeuAc types increased in the iPSCs during cardiomyogenic differentiation. However, the bisecting GlcNAc and the triantennary structures were found in relative abundance in the iPSC-CMs in comparison with hCMCs or iPSCs. Expression of MGAT3, a glycosyltransferase-encoding gene that produces the bisecting GlcNAc structures, was higher in iPSCs and iPSC-CMs than in hCMCs. These findings will prove useful in understanding the directional precision of cardiomyogenic differentiation in vitro., Significance: This study focused on N-glycans produced in human induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes to investigate their change on cardiomyogenic differentiation in vitro. This shows that the expression pattern of N-glycans in human iPSCs changed toward the pattern observed in human cardiomyocytes upon cardiomyogenic differentiation. Structural differences were also observed in the bisecting N-acetylglucosamine and the triantennary structures upon cardiomyogenic differentiation. The findings of this study will help in understanding the directional precision of cardiomyogenic differentiation in vitro., (©AlphaMed Press.)

We performed successful off-pump coronary artery bypass grafting (OPCAB) in a patient with unstable angina caused by triple-vessel disease, who had undergone esophagectomy with substernal gastric tube reconstruction for esophageal cancer 40 years earlier. Preoperative multidetector-row computed tomography was done to evaluate the course of the gastric tube and also that of the gastroepiploic artery, which feeds the gastric tube. Following careful sternal re-entry and adequate dissection, OPCAB was performed safely via a median sternotomy without injuring the gastric tube or causing hemodynamic instability. The patient had an uneventful early postoperative course.

Recent evidence suggests that transcatheter aortic valve replacement (TAVR) is feasible for treating severe aortic valve stenosis (AS) in patients who are considered high risk for elective surgery. However, it is still unclear whether TAVR is a better option than surgical aortic valve replacement for severe AS with acute decompensated heart failure. We report a case of severe AS with acute heart failure, which was treated successfully by urgent TAVR, with cardiopulmonary support.

In contrast to a pulsatile-flow left ventricular assist device (LVAD), an LVAD off test for evaluation of cardiac recovery with a continuous-flow device is difficult because of intra-circuit backflow from the outflow graft when a device is stopped. We report a case of reliable evaluation of cardiac recovery using balloon occlusion of the outflow graft, followed by successful removal of a continuous-flow EVAHEART LVAD using a minimally invasive approach.

Cell surface glycans vary widely, depending on cell properties. We hypothesized that glycan expression on induced pluripotent stem cells (iPSCs) might change during cardiomyogenic differentiation toward the myocardial phenotype. N-glycans were isolated from iPSCs, iPSC-derived cardiomyocytes (iPSC-CM), and original C57BL/6 mouse myocardium (Heart). Their structures were analyzed by a mapping technique based on HPLC elution times and MALDI-TOF/MS spectra. Sixty-eight different N-glycans were isolated; the structures of 60 of these N-glycans were identified. The quantity of high-mannose type (immature) N-glycans on the iPSCs decreased with cardiomyogenic differentiation, but did not reach the low levels observed in the heart. We observed a similar reduction in neutral N-glycans and an increase in fucosylated or sialyl N-glycans. Some structural differences were detected between iPSC-CM and Heart. No N-glycolyl neuraminic acid (NeuGc) structures were detected in iPSC-CM, whereas the heart contained numerous NeuGc structures, corresponding to the expression of cytidine monophosphate-N-acetylneuraminic acid hydroxylase. Furthermore, several glycans containing Galα1-6 Gal, rarely identified in the other cells, were detected in the iPSC-CM. The expression of N-glycan on murine iPSCs changed toward the myocardial phenotype during cardiomyogenic differentiation, leaving the structural differences of NeuGc content or Galα1-6 Gal structures. Further studies will be warranted to reveal the meaning of the difference of N-glycans between the iPSC-CM and the myocardium.

Background: N-glycans isolated from neonatal porcine islet-like cell clusters (NPCCs) were analyzed by a mapping technique, to examine the differences in glycosylation and antigenicity between adult pig islets (APIs) and NPCCs., Methods: NPCCs were isolated from 1-to-3 day-old neonatal wild-type pigs and cultured for 9 days, using the technique described by Korbutt et al. The extract was proteolyzed by treatment with a chymotrypsin and trypsin mixture and further digested with glycoamidase A to release the N-glycans. After the removal of the peptide materials, the reducing ends of the N-glycans were derivatized with 2-aminopyridine. This mixture was applied to DEAE, amide and ODS columns. PA-oligosaccharides were also subjected to MALDI TOF-MS analysis., Results: The NPCC glycans were comprised of 14 neutral, 5 mono-sialyl and 5 di-sialyl glycans. As a feature of the N-glycans of NPCC, NPCC contained large amounts of high mannose structures. On the other hand, all of the hybrid and complex types contained a Fucα1-6GlcNAc structure, but were not modified with sulfate residues. Among them, the NPCC preparation contained five neutral and two mono-sialyl glycans and two di-sialyl glycans that were not typically found in adult islets, and seven of these nine were not detected in human islets. Moreover, most of the structures could be clearly identified in this study., Conclusions: The data herein will be helpful for future studies of the glycoantigen associated with NPCC., (Copyright © 2014 Elsevier B.V. All rights reserved.)