Suk-Won Song

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium†‡

Mesenchymal stem cells (MSCs) therapy has limitations due to the poor viability of MSCs after cell transplantation. Integrin‐mediated adhesion is a prerequisite for cell survival. As a novel anti‐death strategy to improve cell survival in the infarcted heart, MSCs were genetically modified to overexpress integrin‐linked kinase (ILK). The survival rate of ILK‐transfected MSCs (ILK‐MSCs) was augmented by about 1.5‐fold and the phosphorylation of ERK1/2 and Akt in ILK‐MSCs were increased by about three and twofold, respectively. ILK‐MSCs demonstrated an increase of twofold in the ratio of Bcl‐2/Bax and inhibited caspase‐3 activation, compared with hypoxic MSCs. The adhesion rate of ILK‐MSCs also had a 32.2% increase on the cardiac fibroblast‐derived three‐dimensional matrix and ILK‐MSCs showed higher retention by about fourfold compared to unmodified MSCs. Six animals per group were used for the in vivo experiments analyzed at 1 week after occlusion of the left coronary artery. ILK‐MSC transplanted rats had a 12.0% ± 3.1% smaller infarct size than MSC‐treated rats after ligation of left anterior descending coronary artery. Transplantation of ILK‐MSCs not only led to a 16.0% ± 0.4% decrease in the fibrotic heart area, but also significantly reduced the apoptotic positive index by two‐thirds when compared with ligation only. The mean microvessel count per field in the infarcted myocardium of ILK‐MSCs group was increased relative to the sham group and MSCs group. In conclusion, the ILK gene transduction of MSCs further assisted cell survival and adhesion, and improved myocardial damage when compared with MSC only after transplantation. STEM CELLS 2009;27:1358–1365

Effects of partial thrombosis on distal aorta after repair of acute DeBakey type I aortic dissection

OBJECTIVE Prognostic implications of partial thrombosis of the residual aorta after repair of acute DeBakey type I aortic dissection have not been elucidated. We sought to analyze the impact of partial thrombosis on segmental growth rates, distal aortic reprocedures, and long-term survival. METHODS A total of 118 consecutive patients (55% were male; mean age, 60 years) with acute DeBakey type I aortic dissection underwent surgical repair (1997-2007). The hospital mortality rate was 17.8%. Survivors underwent serial computed tomography scans. Segment-specific average rates of enlargement were analyzed. Distal reprocedures and patient survival were examined. RESULTS Sixty-six patients had imaging data sufficient for growth rate calculations. The median diameters within 2 weeks after repair were as follows: aortic arch, 3.5 cm; descending aorta, 3.6 cm; and abdominal aorta, 2.4 cm. Subsequent growth rates were artic arch, 0.34 mm/y, descending aorta, 0.51 mm/y, and abdominal aorta, 0.35 mm/y. Partial thrombosis of the residual aorta predicted greater growth in the distal aorta (P = .005). There were 13 distal aortic reprocedures (5 reoperations, 8 stent graft insertions) for 10 years, and reprocedure-free survival was 66%. Partial thrombosis (P = .002) predicted greater risk of aorta-related reprocedures. Cox analysis revealed that estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) (P = .030), reintubation (P = .002), and partial thrombosis (P = .023) were independent predictors for poor survival. CONCLUSION Partial thrombosis of the false lumen after repair of acute DeBakey type I aortic dissection, compared with complete patency or complete thrombosis, is a significant independent predictor of aortic enlargement, aorta-related reprocedures, and poor long-term survival.

Eight-Year Outcomes of Tricuspid Annuloplasty Using Autologous Pericardial Strip for Functional Tricuspid Regurgitation

BACKGROUND Although several techniques of tricuspid annuloplasty have been used to treat tricuspid regurgitation (TR), TR can persist or recur with redilatation of the annulus or disease progression. We compared the long-term results of newly developed tricuspid annuloplasty procedure using autologous pericardial strip with that of conventional suture annuloplasty. METHODS From January 1997 to April 2006, 334 patients (mean age, 52.7 years) underwent tricuspid annuloplasty for functional TR. Concomitant procedures included mitral valve replacement in 261 patients and mitral-aortic valve replacement in 73. We performed conventional suture annuloplasty (De Vega or Kay) in 117 patients and autologous pericardial strip annuloplasty in 217 patients. RESULTS There were 8 in-hospital deaths (mortality, 2.4%). Mean follow-up was 42.1 months, and total follow-up duration was 1,145 patient-years. Significant TR before discharge was noted in 34 patients (11.1%). The severity of TR improved with time in the autologous pericardial strip annuloplasty group; however, it became worse in conventional suture annuloplasty group (p = 0.05). Multivariate analysis demonstrated that preoperative severity of TR and conventional suture annuloplasty were significant predictors of recurrent TR. Overall survival was comparable between two groups (p = 0.742); however, recurrence-free survival was better for the autologous pericardial strip annuloplasty group than for the conventional suture annuloplasty group (86.8% versus 71.9%; p = 0.039). CONCLUSIONS The long-term recurrence-free survival after autologous pericardial strip annuloplasty appeared to be better than that of conventional suture annuloplasty. Autologous pericardial strip annuloplasty appears to be a simple, easily reproducible, and valid option for surgical treatment of functional TR.

Prognostic factors for aorta remodeling after thoracic endovascular aortic repair of complicated chronic DeBakey IIIb aneurysms

OBJECTIVES The use of thoracic endovascular aortic repair (TEVAR) for chronic DeBakey III type b (CDIIIb) aneurysms is controversial. We analyzed the potential prognostic factors affecting aorta remodeling after this procedure. METHODS A total of 20 patients with CDIIIb aneurysms underwent TEVAR, with full coverage of reentry tears at the descending thoracic aorta. The potential factors affecting false lumen (FL) remodeling were analyzed, including reentry tears (communicating channels visible on the computed tomography angiogram), large intimal tears below the stent graft (≥ 2 consecutive axial cuts on the computed tomography angiogram), visceral branches arising from the FL, and intercostal arteries (ICAs) arising from the FL. RESULTS All the patients had uneventful in-hospital courses; 2 patients (10%) required reintervention during the follow-up period. Thirteen patients (65%) had complete thrombosis of the FL at stent graft segment. Compared with the complete thrombosis group, the partial thrombosis group had more reentry tears (1.8 vs 2.3, P = .48), large intimal tears (0.8 vs 1.7, P < .05), visceral branches arising from the FL (1.2 vs 2.3, P < .05), and ICAs arising from the FL (3.8 vs 5.1, P = .35). Reentry tears, visceral branches, and ICAs from the FL were significant negative prognostic factors for FL shrinkage (P < .05). CONCLUSIONS Although reentry tears above the celiac trunk were fully covered, the visceral branches and ICAs from the FL and all communicating channels below the celiac trunk kept the FL pressurized and were unfavorable prognostic factors for aorta remodeling after TEVAR for CDIIIb aneurysms.

Comparison of Long-Term Outcome of Off-Pump Coronary Artery Bypass Grafting Versus Drug-Eluting Stents in Triple-Vessel Coronary Artery Disease

After the introduction of drug-eluting stents (DESs), percutaneous coronary intervention with DESs has challenged coronary artery bypass grafting as the gold standard for the treatment of 3-vessel coronary artery disease. The purpose of this study was to compare the long-term clinical results between percutaneous coronary intervention with DESs and off-pump coronary artery bypass grafting (OPCAB) in 3-vessel coronary artery disease. Two hundred ninety propensity-score matched patients with 3-vessel coronary artery disease treated by DESs or OPCAB were included. Mean follow-up duration was 58.8 ± 11.5 months (2 to 73) and follow-up rate was 97.9%. Five-year survival rates were 94.8 ± 2.1% in the DES group and 96.5 ± 1.5% in the OPCAB group (p = 0.658). Five-year rates of freedom from major adverse cardiac and cerebrovascular event were 71.6 ± 4.1% in the DES group and 89.6 ± 2.5% in the OPCAB group (p < 0.001). Freedom from nonfatal myocardial infarction and target vessel revascularization rates were the determining factors between the 2 groups (p = 0.018 and p < 0.001, respectively). The OPCAB group showed better clinical outcomes compared to the DES group in 3-vessel coronary artery disease after 5-year follow-up. Freedom from major adverse cardiac and cerebrovascular event rate was significantly higher in the OPCAB group mainly because of the lower incidence of target vessel revascularization and nonfatal myocardial infarction. Longer follow-up with randomization will clarify our present conclusions.

Midterm Outcome of Off-Pump Bypass Procedures Versus Drug-Eluting Stent for Unprotected Left Main Coronary Artery Disease

BACKGROUND Although surgical revascularization is recommended for the treatment of left main coronary artery (LMCA) disease, percutaneous coronary intervention (PCI) attempts have increased, especially after the introduction of the drug-eluting stent. The goal of this study was to compare the midterm outcomes between drug-eluting stenting and off-pump coronary artery bypass (OPCAB) grafting in LMCA disease. METHODS Five hundred twelve consecutive patients with unprotected LMCA disease who underwent OPCAB (N = 269) or drug-eluting stenting (N = 243) were enrolled. We compared major cardiac and cerebrovascular events (MACCEs) in a real-world cohort and in a matching patient cohort (N = 256). The duration of mean follow-up was 38 ± 20 months, and the follow-up rate was 97.7%. RESULTS In a real-world comparison, the OPCAB group showed better 5-year freedom from MACCEs compared with the stenting group (71.5% ± 4.4% versus 67.6% ± 4.0%; p = 0.031), despite worse patient characteristics. After patient matching, the OPCAB group showed more distinct benefit in 5-year freedom from MACCEs (75.3% ± 6.6% versus 62.8% ± 5.4; p < 0.001), including a significantly lower target vessel revascularization (TVR) rate (p < 0.001). In a subgroup analysis, the benefit of OPCAB regarding 5-year freedom from MACCEs was more clearly defined for lesions of the distal LCMA and in LMCA lesions with multivessel disease (p = 0.015, p = 0.004, respectively). CONCLUSIONS Patients with LMCA disease who were treated with OPCAB showed better 5-year freedom from MACCEs in a real-world practice and in a patient matching cohort compared with the drug-eluting stenting group. TVR was the main factor that made the difference. The benefit of OPCAB was more prominent in distal LMCA lesions and in LMCA lesions with multivessel involvement.

Proteomic Analysis and Identification of Paracrine Factors in Mesenchymal Stem Cell-Conditioned Media under Hypoxia

Background/Aims: We previously showed that a hypoxic environment modulates the antiarrhythmic potential of mesenchymal stem cells. Methods: To investigate the mechanism by which secreted proteins contribute to the pathogenesis of antiarrhythmic potential in mesenchymal stem cells, we used two-dimensional electrophoresis combined with MALDI-TOF-MS to perform a proteomic analysis to compare the paracrine media produced by normoxic and hypoxic cells. Results: The proteomic analysis revealed that 66 protein spots out of a total of 231 matched spots indicated differential expression between the normoxic and hypoxic conditioned media of mesenchymal stem cells. Interestingly, two tropomyosin isoforms were dramatically increased in the hypoxic conditioned medium of mesenchymal stem cells. An increase in tropomyosin was confirmed using Western blot to analyze the conditioned media between normoxic and hypoxic cells. In a network analysis based on gene ontology (GO) Molecular Function by GeneMANIA analysis, most of the identified proteins were found to be involved in the regulation of heart processes. Conclusion: Our results show that hypoxia up-regulates tropomyosin and other secreted proteins which suggests that tropomyosin may be involved in regulating proarrhythmic and antiarrhythmic functions.

Open Pulmonary Thromboembolectomy in Patients with Major Pulmonary Thromboembolism

Purpose We retrospectively analyzed open pulmonary thromboembolectomy in patients with acute and chronic pulmonary thromboembolism. Materials and Methods Between August 1990 and May 2005, 12 consecutive patients with acute and chronic pulmonary thromboembolism underwent open pulmonary thromboembolectomy at Yonsei Cardiovascular Center. Their mean age was 47.5 years, and 7 of the patients were female. Among 12 patients, 5 had acute onset, and 7 had chronic disease, and 9 patients were associated with deep venous thrombosis. Extent of pulmonary embolism was massive in 3 patients with hemodynamic instability, and submassive in 8 patients. Preoperative echocardiogram revealed elevated right ventricular pressure in all patients, and 7 patients were in NYHA functional class III or IV. Pulmonary thromboembolectomy was performed in all patients under total circulatory arrest. Results There were 2 hospital deaths (16.7%). Among the patients who survived, mean right ventricular pressure was decreased significantly from 64.3 mmHg to 34.0 mmHg with improvement of NYHA functional class. Conclusion Open pulmonary thromboembolectomy is thought to be an immediate and definitive treatment for massive pulmonary embolism with optimal results. Even though operative mortality is still high, early diagnosis and immediate surgical intervention in highly selective patients may improve the clinical outcome.

Pulmonary Embolism Caused by Popliteal Venous Aneurysm

Venous aneurysms are uncommon in the lower limb and are more frequently found in the neck and thoracic and visceral veins. However, they have been reported to cause thrombosis, pulmonary thromboembolism, and other related complications. Popliteal venous aneurysms are often undetected because they are usually asymptomatic, but they may cause pulmonary thromboembolic events. We experienced a case of a 44-year-old man who was referred for recurrent pulmonary thromboembolism. He showed no other symptoms or signs except shortness of breath. A popliteal venous aneurysm was diagnosed incidentally because the examinations were performed to detect a deep vein thrombosis in relationship to the patients history of pulmonary thromboembolism. We report a case of surgical treatment for a popliteal venous aneurysm that was complicated by pulmonary thromboembolism.

Comparison of the radial artery and saphenous vein as composite grafts in off-pump coronary artery bypass grafting in elderly patients: a randomized controlled trial.

Background and Objectives Arterial grafts have a better long-term patency rate than saphenous vein (SV) when used in off-pump coronary artery bypass surgery (OPCAB). However, arterial grafts in elderly patients are often diseased. We sought to compare the early outcomes achieved by using the two different types of composite grafts. Subjects and Methods We conducted a randomized trial to compare radial artery (RA) and SV composite grafts based on the in situ left internal mammary artery in 60 elderly (>70 years old) patients, who were scheduled to undergo OPCAB. Clinical outcomes and 1-year postoperative CT angiography results were compared. The quality of the conduit was evaluated by employing vascular ultrasonography, optical coherence tomography (OCT), and histologic examination. Results No differences in immediate postoperative morbidity and mortality were observed between the two groups. Early postoperative CT angiography revealed a SV patency rate of 100%, which was not different from that of RA composite grafts (99.1%). CT angiography after a year showed an overall patency rate of 96.3%. The overall patency rate of the SV group at 1 year was 94.7%, which was similar to that of the RA group (97.4%). Also, there was no difference in overall survival rate between the two groups. Vascular ultrasonographic images showed strong correlations between OCT and histopathology. Conclusion Our analysis of early outcomes revealed that the SV could be used as an alternative composite graft to the RA in elderly patients. Vascular ultrasonography is an accurate, real-time, and reproducible method for assessing the quality of the RA conduit.