Effect of morphological change on the maturation of human induced pluripotent stem cell-derived cardiac tissue in rotating flow culture.

Introduction: Understanding the critical factors for the maturation of human induced pluripotent stem cell (hiPSC)-derived cardiac tissue is important for further development of culture techniques. Rotating flow culture, where the tissues float in the culture medium by balancing its gravitational settling and the medium flow generated in rotating disk-shaped culture vessels, is one of culture systems used for tissue engineering. It has previously been demonstrated that rotating flow culture leads to the formation of matured cardiac tissue with higher levels of function and structure than the other culture systems. However, the detailed mechanisms underlying the maturation of cardiac tissue remain unclear. This study investigated the maturation process of hiPSC-derived cardiac tissue in rotating flow culture with a focus on morphological changes in the tissue, which is a trigger for maturation. Methods: The cardiac tissue, which consisted of cardiomyocytes derived from hiPSCs, was cultured on the 3D scaffold of poly (lactic-co-glycolic) acid (PLGA)-aligned nanofibers, in rotating flow culture for 5 days. During the culture, the time profile of projected area of tissue and formation of maturation marker proteins (ß-myosin heavy chain and Connexin-43), tissue structure, and formation of nuclear lamina proteins (Lamin A/C) were compared with that in static suspension culture. Results: The ratio of the projected area of tissue significantly decreased from Day 0 to Day 3 due to tissue shrinkage. In contrast, Western blot analysis revealed that maturation protein markers of cardiomyocytes significantly increased after Day 3. In addition, in rotating flow culture, flat-shaped nuclei and fiber-like cytoskeletal structures were distributed in the surface region of tissue where medium flow was continuously applied. Moreover, Lamin A/C, which are generally formed in differentiated cells owing to mechanical force across the cytoskeleton and critically affect the maturation of cardiomyocytes, were significantly formed in the tissue of rotating flow culture. Conclusions: In this study, we found that spatial heterogeneity of tissue structure and tissue shrinkage occurred in rotating flow culture, which was not observed in static suspension culture. Moreover, from the quantitative analysis, it was also suggested that tissue shrinkage in rotating flow culture contributed its following tissue maturation. These findings showed one of the important characteristics of rotating flow culture which was not revealed in previous studies.

Successful "PETTICOAT" procedure assisted by aortic angioscopy for complicated type B aortic dissection: Case report.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) is a useful treatment for acute type B aortic dissection (TBAD). A PETTICOAT (Provisional ExTension to Induce COmplete ATtachment) procedure can be an alternative surgical option for a patent false lumen. Non-obstructive aortic angioscopy is an attractive modality that can visualize the aortic intima for things such as entry or re-entry tears that are difficult to detect with computed tomography (CT). Herein, we describe a successful PETTICOAT procedure assisted by aortic angioscopy for subacute TBAD complicated by lower limb ischemia. PRESENTATION OF CASE: A 63-year-old man who had been treated with conservative therapy for subacute TBAD had intermittent claudication. Enhanced CT revealed a primary entry tear at the distal arch, and the true lumen at the thoracoabdominal level was narrowed by the patent false lumen. Therefore, the PETTICOAT procedure was performed. The postoperative course was uneventful, with normalized lower limb pressure. DISCUSSION: Although PETTICOAT procedure is effective for treating complicated TBAD, there is no consensus on where and how far the proximal stent graft or distal bare stent should be implanted. Non-obstructive aortic angioscopy during PETTICOAT is useful to detect and cover the entry and re-entry tears. The PETTICOAT procedure assisted by aortic angioscopy could contribute to determining the appropriate coverage range of the stent graft. CONCLUSION: Aortic angioscopy could contribute to the surgical success of PETTICOAT procedure for complicated subacute TBAD.

Engineered three-dimensional cardiac tissues maturing in a rotating wall vessel bioreactor remodel diseased hearts in rats with myocardial infarction.

A rotating wall vessel (RWV) bioreactor was constructed for growing massive functional cardiac constructs to recover the function of a distressed rat heart. Three-dimensional cardiac tissues were engineered by seeding human-induced pluripotent stem cell-derived cardiomyocytes on poly(lactic-co-glycolic acid) fiber sheets (3D-hiPSC-CTs) and cultured in the RWV bioreactor (RWV group) or under static conditions (control group). The tissues were transplanted into a myocardial infarction nude rat model, and cardiac performance was evaluated. In the RWV group, cell viability and contractile and electrical properties significantly improved, mature cardiomyocytes were observed, and mechanical stress-related mediators of mammalian target of rapamycin signaling were upregulated compared with those of the control. Four weeks post-transplantation, tissue survival and left ventricular ejection fraction significantly improved in the RWV group. Hence, dynamic culture in an RWV bioreactor could provide a superior culture environment for improved performance of 3D-hiPSC-CTs, providing a means for functional cardiomyogenesis in myocyte-loss heart failure.

Impact of tricuspid regurgitation on late right ventricular failure in left ventricular assist device patients ~can prophylactic tricuspid annuloplasty prevent late right ventricular failure? ~.

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.

Midterm Clinical Outcomes of the St Jude Medical Epic Porcine Bioprosthesis in the Mitral Position.

BACKGROUND: The aim of this single-center study was to report the midterm clinical outcomes and hemodynamic performance of the St Jude Medical Epic porcine bioprosthesis, a tricomposite glutaraldehyde-preserved porcine bioprosthesis, in mitral position. Methods and Results: Between January 2011 and March 2017, 117 patients (62 men, 55 women; mean age, 66.7±12.8 years) who underwent mitral valve replacement (MVR) with the Epic valve were retrospectively analyzed for early and mid-term morbidity and mortality. The mean follow-up period was 2.6±1.7 years. Three operative deaths occurred, and the operative mortality rate was 2.6%. Sixteen patients died during the follow-up period. On Kaplan-Meier analysis, freedom from all-cause death and major adverse cardiovascular and cerebrovascular events at 5-year follow-up were 80.9% and 54.8%, respectively. There were 6 reoperations: 2 for structural valve deterioration (SVD), 2 for prosthetic valve endocarditis, and 2 for thrombosis. Freedom from valve-related reoperation and SVD at 5 years were 89.0% and 93.1%, respectively. On multivariate analysis, age ≥71 years (HR, 6.78; 95% CI: 2.12-25.2, P<0.01), and NYHA functional class ≥III (HR, 3.20; 95% CI: 1.03-10.4, P=0.04) were independent predictors for all-cause death. Mean mitral pressure gradient at 1 year and 2 years were 5.1±1.9 mmHg and 4.5±1.4 mmHg, respectively. CONCLUSIONS: Mid-term clinical results and durability of the Epic valve in the mitral position are satisfactory.

Systolic anterior motion of the mitral valve masked by general anesthesia.

Systolic anterior motion of the mitral valve is usually associated with hypertrophic obstructive cardiomyopathy that results in left ventricular outflow tract obstruction. This is sometimes treated by volume loading or negative inotropics such as beta blockers. We report a rare case of dynamic systolic anterior motion of the mitral valve, in which a beta blocker did not diminish but anesthetic agents masked intraoperatively. The patient underwent mitral valve replacement, and left ventricular outflow tract obstruction was successfully treated.

Preoperative estimated glomerular filtration rate is an independent predictor of late cardiovascular morbidity after mitral valve surgery.

PURPOSE: Renal dysfunction affects outcomes of cardiac surgery, although its role in mitral valve operation has been limitedly documented. METHODS: Two hundred and ten patients who underwent mitral valve operation between 2004 and 2011 were divided into 3 groups according to preoperative estimated glomerular filtration ratio (eGFR): group A (eGFR ≥60 ml/min/1.73 m(2), n = 102), group B (eGFR, 59-30 ml/min/1.73 m(2), n = 92) and group C (eGFR <30 ml/min/1.73 m(2), n = 16). RESULTS: Freedom from all-cause and cardiovascular death at 5 years was 77.2% and 93.0%, respectively. No significant differences existed between the 3 groups. In contrast, there was a significant difference in freedom from major adverse cardiovascular events (MACE) between groups (70.4%, 57.1%, and 42.8% in group A, B, and C, respectively; p = 0.008). By univariate and multivariate analysis, eGFR <60 ml/min/1.73 m(2) (HR: 1.92, 95% CI: 1.02-3.68, p = 0.044) and left ventricular ejection fraction <40% (HR: 2.69, 95% CI: 1.17-6.23, p = 0.02) were independent risk factors of MACE, although serum creatinine failed to represent an independent risk factor. CONCLUSION: Patients who underwent mitral valve surgery had acceptable perioperative and long-term survival, irrespective of preoperative renal function. However, eGFR <60 ml/min/1.73 m(2) was an independent predictor of late MACE.

Beating heart mitral valve repair for a patient with previous coronary bypass: a case report and review of the literature.

Mitral valve reoperation, through a median sternotomy, for a patient with patent coronary bypass grafts is technically challenging and carries higher postoperative morbidity and mortality than a primary operation. We present a case of mitral valve repair using a beating heart technique under normothermic cardiopulmonary bypass that was performed 3 years after a coronary artery bypass operation. A limited (10 cm) right thoracotomy was made and cardiopulmonary bypass was conducted using the ascending aortic and femoral venous cannulation. The left atrium was opened while beating was maintained. Triangular resection of the prolapsed portion of the posterior leaflet and ring annuloplasty were performed. Completeness of the repair was verified by direct visualization under beating condition and transesophageal echocardiogram. This technique is a safe and feasible option for a mitral valve reoperation that excludes re-sternotomy, extensive pericardial dissection and aortic clamping, thereby minimizes risks of bleeding, graft injury and myocardial damage.