Byung Chul Chang

Small-diameter blood vessels engineered with bone marrow-derived cells

Objective:The objective of this study is to investigate if bone marrow–derived cells (BMCs) regenerate vascular tissues and improve patency in tissue-engineered small-diameter (internal diameter = 3 mm) vascular grafts. Summary Background Data:BMCs have demonstrated the ability to differentiate into endothelial-like cells and vascular smooth muscle–like cells and may offer an alternative cell source for vascular tissue engineering. Thus, we tissue-engineered small-diameter vascular grafts with BMCs and decellularized arteries. Methods:Canine BMCs were differentiated in vitro into smooth muscle α-actin/smooth muscle myosin heavy-chain-positive cells and von Willebrand factor/CD31-positive cells and seeded onto decellularized canine carotid arteries (internal diameter = 3 mm). The seeded grafts were implanted in cell donor dogs. The vascular-tissue regeneration and graft patency were investigated with immunohistochemistry and angiography, respectively. Results:The vascular grafts seeded with BMCs remained patent for up to 8 weeks in the canine carotid artery interposition model, whereas nonseeded grafts occluded within 2 weeks. Within 8 weeks after implantation, the vascular grafts showed regeneration of the 3 elements of artery (endothelium, media, and adventitia). BMCs labeled with a fluorescent dye prior to implantation were detected in the retrieved vascular grafts, indicating that the BMCs participated in the vascular tissue regeneration. Conclusions:Here we show that BMCs have the potential to regenerate vascular tissues and improve patency in tissue-engineered small-diameter vascular grafts. This is the first report of a small-diameter neovessel engineered with BMCs as a cell source.

Prediction of cognitive dysfunction and patients' outcome following valvular heart surgery and the role of cerebral oximetry.

OBJECTIVEnPostoperative cognitive dysfunction (POCD) commonly develops after cardiac surgery affecting patients outcome. Cerebral oximetry noninvasively measures regional cerebral oxygen saturation (rSO(2)) and significant correlation has been reported between intraoperative cerebral desaturation and POCD, as well as patients outcome following coronary artery bypass grafting. However, evidence is limited in valvular heart surgery (VHS). We investigated the relationship of intraoperative rSO(2) values with POCD and length of postoperative hospitalization in patients undergoing VHS.nnnMETHODSnOne hundred patients undergoing elective VHS were enrolled. Neurocognitive evaluation was performed with Mini-Mental State Examination, Trail-Making Test (Part A), and Grooved Pegboard Test at 1 day before and 7th day after surgery. During surgery, rSO(2) was continuously monitored and the incidence and duration of decrease in rSO(2) values for five consecutive minutes were recorded as follows; (1) decrease in absolute rSO(2) values to less than 50%, (2) 40%, and (3) a 20% decrease compared to baseline value.nnnRESULTSnTwenty-three patients (23%) demonstrated POCD. We could not observe any significant differences in either the incidence or duration of decrease in rSO(2) values between patients with and without POCD. Low education level and higher baseline temperature had significant correlation with POCD. Patients with cerebral desaturation required significantly longer postoperative hospitalization.nnnCONCLUSIONnIn patients undergoing VHS, POCD could not be predicted with cerebral oximetry. However, patients with intraoperative cerebral desaturation required significantly longer postoperative hospitalization and cerebral oximetry appears to be promising in terms of monitoring the brain as the index organ for systemic perfusion and improving patients outcome.

Stent-graft treatment of infected aortic and arterial aneurysms.

Purpose: To evaluate the feasibility and effectiveness of endovascular stent-graft repair of infected aortic and arterial aneurysms. Methods: Eight patients (5 men; mean age 56.6 years, range 30–85) with infected saccular aneurysms in the brachiocephalic artery (n=1), proximal descending thoracic aorta (n=1), infrarenal abdominal aorta (n=3), common iliac artery (n=1), and common femoral artery (n=2) were treated with stent-graft placement and intravenous antibiotic treatment for at least 6 weeks followed by case-specific administration of oral suppressive antibiotics. All patients were considered to be in the high-surgical-risk group. Results: Exclusion of the infected aneurysm was successful in all patients. However, 2 patients died within 30 days of uncontrolled sepsis, and 1 patient died at 6 months after rupture of a persistently infected aneurysm (37% mortality rate). Over a follow-up that ranged to 8 years, the 5 survivors showed complete resolution of the infected aneurysms; no stent-graft infection was observed during follow-up. Conclusion: The acceptable technical and clinical success of endovascular aneurysm repair makes this a promising treatment for infected aortic and arterial aneurysms. However, it is crucial that the infection is treated adequately prior to stent-graft placement.

Prediction of Left Atrial Fibrosis With Speckle Tracking Echocardiography in Mitral Valve Disease: A Comparative Study With Histopathology

Background and Objectives Left atrial (LA) fibrosis is a main determinant of LA remodeling and development of atrial fibrillation. However, non-invasive prediction of LA fibrosis is challenging. We investigated whether preoperative LA strain as measured by speckle tracking echocardiography could predict the degree of LA fibrosis and LA reverse remodeling after mitral valve (MV) surgery. Subjects and Methods Speckle tracking echocardiography and LA volume measurements were performed in 50 patients one day before MV surgery. LA tissues were obtained during the surgery, and the degrees of their interstitial fibroses were measured. LA volume measurements were repeated within 30 days after surgery (n=50) and 1-year later (n=39). Results Left atrial global strain was significantly correlated with the degree of LA fibrosis (r=-0.55, p<0.001), and its correlation was independent of age, underlying rhythm, presence of rheumatic heart disease and type of predominant MV disease (B=-1.37, 95% confidence interval -2.32 - -0.41, p=0.006). The degree of LA fibrosis was significantly correlated with early (r=-0.337, p=0.017) and 1-year (r=-0.477, p=0.002) percent LA volume reduction after MV surgery, but LA global strain was not significant. Conclusion Left atrial strain as measured by speckle tracking echocardiography might be helpful for predicting the degree of LA fibrosis in patients with MV disease.

Overexpression of Transforming Growth Factor-β1 in the Valvular Fibrosis of Chronic Rheumatic Heart Disease

For the purpose of determining the pathogenic role of transforming growth factor-β1 (TGF-β1) in the mechanism of chronic rheumatic heart disease, we evaluated the expression of TGF-β1, proliferation of myofibroblasts, and changes in extracellular matrix components including collagen and proteoglycan in 30 rheumatic mitral valves and in 15 control valves. High TGF-β1 expression was identified in 21 cases (70%) of rheumatic mitral valves, whereas only 3 cases (20%) of the control group showed high TGF-β1 expression (p<0.001). Additionally, increased proliferation of myofibroblasts was observed in the rheumatic valves. High TGF-β1 expression positively correlated with the proliferation of myofibroblasts (p=0.004), valvular fibrosis (p<0.001), inflammatory cell infiltration (p=0.004), neovascularization (p=0.007), and calcification (p<0.001) in the valvular leaflets. The ratio of proteoglycan to collagen deposition inversely correlated with TGF-β1 expression in mitral valves (p=0.040). In conclusion, an ongoing inflammatory process, the expression of TGF-β1, and proliferation of myofibroblasts within the valves have a potential role in the valvular fibrosis, calcification, and changes in the extracellular matrix that lead to the scarring sequelae of rheumatic heart disease.

Elective stent-graft treatment of aortic dissections.

Purpose: To retrospectively review 8 years experience with stent-graft treatment of aortic dissections at a single institution. Methods: Forty-six patients (31 men; mean age 59 years, range 38–88) underwent stent-graft treatment for 9 Stanford type A and 37 type B aortic dissections (9 acute phase, 13 subacute, 24 chronic). Custom-designed self-expanding stainless steel Z stents covered with polytetrafluoroethylene were used (n=20) until low-profile modular stent-grafts became available for percutaneous delivery (n=26). Results: Endovascular stent-graft deployment was technically successful in 44 (96%) patients; the 2 failed cases owing to intraprocedural migration and graft torsion were converted to surgery. There were 5 type I endoleaks for a clinical success (entry tear exclusion) of 85% (39/46). Complications included 3 cases of transient renal failure, 2 puncture site pseudoaneurysms, 1 guidewire-induced new intimal tear (converted), and 2 cases of stent-induced saccular aneurysms (1 converted). Follow-up at a mean 34 months (range 12–96) showed complete resolution of the thoracic false lumen in 14 (74%) of 19 acute/subacute patients treated successfully; 3 (16%) showed a reduced thoracic false lumen diameter. In the 23 chronic-phase patients treated successfully, 8 (35%) had complete resolution of the thoracic false lumen, and 11 (48%) showed size reduction. Enlargement of the abdominal aortic false lumen due to persistent flow into re-entry tear(s) occurred in 3 (13%). Conclusions: Stent-graft treatment is a feasible and effective treatment modality in aortic dissection. However, close follow-up is mandatory to monitor new intimal tear, saccular aneurysms, or enlargement of the abdominal aortic false lumen.

Tissue engineering of heart valves by recellularization of glutaraldehyde-fixed porcine valves using bone marrow-derived cells

To increase the biocompatibility and durability of glutaraldehyde (GA)-fixed valves, a biological coating with viable endothelial cells (ECs) has been proposed. However, stable EC layers have not been formed successfully on GA-fixed valves due to their inability to repopulate. In this study, to improve cellular adhesion and proliferation, the GA-fixed prostheses were detoxified by treatment with citric acid to remove free aldehyde groups. Canine bone marrow mononuclear cells (MNCs) were differentiated into EC-like cells and myofibroblast-like cells in vitro. Detoxified prostheses were seeded and recellularized with differentiated bone marrow-derived cells (BMCs) for seven days. Untreated GA-fixed prostheses were used as controls. Cell attachment, proliferation, metabolic activity, and viability were investigated and cell-seeded leaflets were histologically analyzed. On detoxified GA-fixed prostheses, BMC seeding resulted in uninhibited cell proliferation after seven days. In contrast, on untreated GA-fixed prostheses, cell attachment was poor and no viable cells were observed. Positive staining for smooth muscle a-actin, CD31, and proliferating cell nuclear antigen was observed on the luminal side of the detoxified valve leaflets, indicating differentiation and proliferation of the seeded BMCs. These results demonstrate that the treatment of GA-fixed valves with citric acid established a surface more suitable for cellular attachment and proliferation. Engineering heart valves by seeding detoxified GA-fixed biological valve prostheses with BMCs may increase biocompatibility and durability of the prostheses. This method could be utilized as a new approach for the restoration of heart valve structure and function in the treatment of end-stage heart valve disease.

Is prophylactic aortic valve replacement indicated during mitral valve surgery for mild to moderate aortic valve disease

BACKGROUNDnDetermining the need for surgical treatment of coexisting mild to moderate aortic valve disease in patients referred for mitral valve surgery is often difficult. The purpose of this study was to assess long-term clinical outcome and the need for subsequent aortic valve replacement in patients with mild to moderate rheumatic aortic valve disease at the time of mitral valve surgery.nnnMETHODSnA total of 275 patients (90 men and 185 women, mean age 43 years) with rheumatic disease who underwent mitral valve surgery were followed up for an average of 9 years. Patients were classified into two groups: those with coexisting mild to moderate aortic valve disease at the time of mitral valve surgery (141 patients, group A) and those without (134 patients, group B). Primary outcomes (death and subsequent aortic valve surgery) were compared between the two groups.nnnRESULTSnAt the time of mitral valve surgery, 104 patients (74%) in group A had mild aortic regurgitation, 37 (26%) had moderate aortic regurgitation, 5 had (4%) mild aortic stenosis, and 2 (1%) had moderate aortic stenosis. At the end of follow-up, no patient had severe aortic valve disease. In all, 12 patients (5%) in group A had primary events (eight deaths and four subsequent aortic valve replacements), and 12 patients (9%) in group B had such events (12 deaths). According to Kaplan-Meier analysis, neither the survival rate nor the event-free survival rate differed significantly over the follow-up period between the two groups.nnnCONCLUSIONSnIn most patients who have mild to moderate rheumatic aortic valve disease at the time of mitral valve surgery, the long-term outcome is comparable to that of subjects without aortic valve disease at the time of mitral valve surgery. Subsequent aortic valve replacement is rarely needed after a long follow-up period.

False aneurysms at both ends of a descending thoracic aortic stent-graft: complication after endovascular repair of a penetrating atherosclerotic ulcer.

Purpose: To report the formation of false aneurysms at both ends of a stent-graft implanted in the descending thoracic aorta to repair a penetrating atherosclerotic ulcer. Case Report: A 66-year-old woman with a penetrating atherosclerotic ulcer was treated with a 34 × 70-mm homemade Gianturco-type stent covered with polytetrafluoroethylene graft. Four months later, she developed false aneurysms at both ends of the stent-graft. The patient refused further endovascular repairs, so the stent-graft was surgically removed and the aorta repaired. Conclusions: This case demonstrates an unusual complication that should be anticipated when a stent-graft is deployed in the acute phase of thoracic aortic ulcer or its variants.

Implementation of a large-scale hospital information infrastructure for multi-unit health-care services:

Summary With the increase in demand for high quality medical services, the need for an innovative hospital information system has become essential. An improved system has been implemented in all hospital units of the Yonsei University Health System. Interoperability between multi-units required appropriate hardware infrastructure and software architecture. This large-scale hospital information system encompassed PACS (Picture Archiving and Communications Systems), EMR (Electronic Medical Records) and ERP (Enterprise Resource Planning). It involved two tertiary hospitals and 50 community hospitals. The monthly data production rate by the integrated hospital information system is about 1.8 TByte and the total quantity of data produced so far is about 60 TByte. Large scale information exchange and sharing will be particularly useful for telemedicine applications.