Sang Yeub Lee

Fractional Flow Reserve and Cardiac Events in Coronary Artery DiseaseClinical Perspective: Data From a Prospective IRIS-FFR Registry (Interventional Cardiology Research Incooperation Society Fractional Flow Reserve)

Background: We evaluated the prognosis of deferred and revascularized coronary stenoses after fractional flow reserve (FFR) measurement to assess its revascularization threshold in clinical practice. Methods: The IRIS-FFR registry (Interventional Cardiology Research In-cooperation Society Fractional Flow Reserve) prospectively enrolled 5846 patients with ≥1coronary lesion with FFR measurement. Revascularization was deferred in 6468 lesions and performed in 2165 lesions after FFR assessment. The primary end point was major adverse cardiac events (cardiac death, myocardial infarction, and repeat revascularization) at a median follow-up of 1.9 years and analyzed on a per-lesion basis. A marginal Cox model accounted for correlated data in patients with multiple lesions, and a model to predict per-lesion outcomes was adjusted for confounding factors. Results: For deferred lesions, the risk of major adverse cardiac events demonstrated a significant, inverse relationship with FFR (adjusted hazard ratio, 1.06; 95% confidence interval, 1.05–1.08; P<0.001). However, this relationship was not observed in revascularized lesions (adjusted hazard ratio, 1.00; 95% confidence interval, 0.98–1.02; P=0.70). For lesions with FFR ≥0.76, the risk of major adverse cardiac events was not significantly different between deferred and revascularized lesions. Conversely, in lesions with FFR ⩽0.75, the risk of major adverse cardiac events was significantly lower in revascularized lesions than in deferred lesions (for FFR 0.71–0.75, adjusted hazard ratio, 0.47; 95% confidence interval, 0.24–0.89; P=0.021; for FFR ⩽0.70, adjusted hazard ratio 0.47; 95% confidence interval, 0.26–0.84; P=0.012). Conclusions: This large, prospective registry showed that the FFR value was linearly associated with the risk of cardiac events in deferred lesions. In addition, revascularization for coronary artery stenosis with a low FFR (⩽0.75) was associated with better outcomes than the deferral, whereas for a stenosis with a high FFR (≥0.76), medical treatment would be a reasonable and safe treatment strategy. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01366404.

Protective Effects of Peroxiredoxin on Hydrogen Peroxide Induced Oxidative Stress and Apoptosis in Cardiomyocytes

Background and Objectives The redox system is an important anti-oxidative system composed of thioredoxin, thioredoxin reductase, and peroxiredoxin (PRx). The fine details of PRx expression and its protective effects in various cells in cardiovascular tissue under oxidative stress created by hydrogen peroxide have not been fully elucidated. Subjects and Methods Oxidative stress was induced by adding hydrogen peroxide at 0.25 mM for 2 hours to rat neonatal cardiomyocytes (rCMCs), rat vascular smooth muscle cells (rVSMCs), and human umbilical vein endothelial cells (HUVECs). Apoptosis was quantified by flow cytometry and the expression patterns of the six PRx isoforms were evaluated by western blotting in the three cell lines after hydrogen peroxide stimulation. Apoptosis and the cell survival signal pathway were evaluated by PRx1 gene delivery using lentiviral vector in hydrogen peroxide stimulated rCMCs versus green fluorescence protein gene delivery. Results Hydrogen peroxide induced 25% apoptosis in rCMCs. Furthermore, the PRx1 and 5 isoforms were found to be overexpressed in hydrogen peroxide treated rCMCs, and PRx1 overexpression by gene delivery was found to reduce hydrogen peroxide induced rCMCs apoptosis significantly. In addition, this effect was found to originate from cell survival pathway modification. Conclusion Hydrogen peroxide induced significant oxidative stress in rCMCs, rVSMCs, and HUVECs, and PRx1 overexpression using a lentiviral vector system significantly reduced hydrogen peroxide induced rCMCs apoptosis by upregulation of cell survival signals and downregulation of apoptotic signals. These findings suggest that PRx1 could be used as a treatment strategy for myocardial salvage in conditions of oxidative stress.

Upstream High-Dose Tirofiban Does Not Reduce Myocardial Infarct Size in Patients Undergoing Primary Percutaneous Coronary Intervention: A Magnetic Resonance Imaging Pilot Study

Primary percutaneous coronary intervention (PCI) is more effective than fibrinolytic therapy for ST‐segment elevation myocardial infarction (STEMI), but initial treatment delay to intervention is the main limitation of this strategy. Hypothesis: Upstream use of high‐dose tirofiban could reduce myocardial infarct size, using analysis of contrast‐enhanced magnetic resonance imaging (CE‐MRI).

A case of sparganosis that presented as a recurrent pericardial effusion.

Sparganosis is caused by a larval tapeworm of the genus Spirometra, which commonly invades subcutaneous tissue, but less frequently invades muscle, intestines, spinal cord, and the peritoneopleural cavity. The authors managed a female patient who presented with a recurrent pericardiopleural effusion and peripheral eosinophilia. The anti-sparganum-specific IgG serum level was significantly higher than normal control levels. In this patient, sparganosis was caused by the ingestion of raw frogs in an effort to control her thyroid disease. The recurrent pericardiopleural effusion and peripheral eosinophilia were controlled by 3 consecutive doses of praziquantel (75 mg/kg/day). The patient is doing well 4 years after presentation. Sparganosis should be considered a rare, but possible cause of recurrent pericardial effusion and peripheral eosinophilia. Immunoserologic testing using enzyme linked immunosorbent assays can be helpful in diagnosing human sparganosis, especially in cases without a subcutaneous lump or mass. Praziquantel is an alternative treatment for sparganosis in surgically-unresectable cases.

Expression Pattern of the Thioredoxin System in Human Endothelial Progenitor Cells and Endothelial Cells Under Hypoxic Injury

Background and Objectives The thioredoxin (TRx) system is a ubiquitous thiol oxidoreductase pathway that regulates cellular reduction/oxidation status. Although endothelial cell (EC) hypoxic damage is one of the important pathophysiologic mechanisms of ischemic heart disease, its relationship to the temporal expression pattern of the TRx system has not yet been elucidated well. The work presented here was performed to define the expression pattern of the TRx system and its correlation with cellular apoptosis in EC lines in hypoxic stress. These results should provide basic clues for applying aspects of the TRx system as a therapeutic molecule in cardiovascular diseases. Subjects and Methods Hypoxia was induced with 1% O2, generated in a BBL GasPak Pouch (Becton Dickinson, Franklin Lakes, NJ, USA) in human endothelial progenitor cells (hEPC) and human umbilical vein endothelial cells (HUVEC). Apoptosis of these cells was confirmed by Annexin-V: Phycoerythrin flow cytometry. Expression patterns of TRx; TRx reductase; TRx interacting protein; and survival signals, such as Bcl-2 and Bax, in ECs under hypoxia were checked. Results Apoptosis was evident after hypoxia in the two cell types. Higher TRx expression was observed at 12 hours after hypoxia in hEPCs and 12, 36, 72 hours of hypoxia in HUVECs. The expression patterns of the TRx system components showed correlation with EC apoptosis and cell survival markers. Conclusion Hypoxia induced significant apoptosis and its related active changes of the TRx system were evident in human EC lines. If the cellular impact of TRx expression pattern in various cardiovascular tissues under hypoxia or oxidative stress was studied meticulously, the TRx system could be applied as a new therapeutic target in cardiovascular diseases, such as ischemic heart disease or atherosclerosis.

A Case of Severe Aortic Valve Regurgitation Caused by an Ascending Aortic Aneurysm in a Young Patient With Autosomal Dominant Polycystic Kidney Disease and Normal Renal Function

Aortic aneurysm is one several well-known cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPCKD). Commonly affected site of aortic aneurysm and its related dissection in ADPCKD is abdominal aorta. Long standing hypertension, haemodialysis, old age are closely related with discovering of aortic aneurysm and dissection in ADPCKD. However, thoracic aortic aneurysms and its related severe aortic regurgitations (ARs) are rare in younger patients suffering from ADPCKD, especially ones who have normal renal function. Here, we report a case involving a 27-year-old Asian male patient with severe AR due to an ascending aneurysm of the thoracic aorta associated with ADPCKD. The patient had normal renal function without Marfans habitus. The AR and thoracic aortic aneurysm were corrected surgically.

Serum thioredoxin 1 level has close relation with myocardial damage amount in acute myocardial infarction patients.

Thioredoxin-1 (Trx-1) is one of important anti-oxidative molecules to overcome the oxidative stress. The aim of the present study is to investigate the clinical relationship between serum concentration of Trx-1 on the pre-percutaneous coronary intervention (prePCI) and myocardial damage amount in the patients with acute myocardial infarction with the culprit lesion in only the left anterior descending artery on coronary angiography (n = 100). Initial value of creatine kinase (CK) was 368.3 ± 531.4 U/L, and MB isoenzyme of CK (CK-MB) level was 22.92 ± 33.8 ng/mL, and cardiac specific troponin T (cTnT) level was 0.61 ± 1.6 ng/mL. Positive correlations were observed between prePCI Trx-1 level and initial CK (P = 0.005, r = 0.281), and cTnT (P < 0.001, r = 0.453), peak CK (P = 0.001, r = 0.316) in all patients, but the statistical relation was observed only in ST segment elevation myocardial infarction (STEMI) patients (P = 0.008, r = 0.329 for initial CK, P = 0.001, r = 0.498 for initial cTnT, P = 0.005, r = 0.349 for peak CK), not in Non-STEMI patients. Conclusively, we consider prePCI serum Trx-1 as a predictor for myocardial damage amount in patients with STEMI.

Pharmacokinetics of a new once-daily controlled-release sarpogrelate hydrochloride compared with immediate-release formulation and the effect of food.

Sarpogrelate is a selective 5‐hydroxytryptamine receptor subtype 2A antagonist that inhibits platelet aggregation and vasoconstriction. The aim of this study was to compare the pharmacokinetics of a sarpogrelate controlled‐release formulation (CR) with those of the immediate‐release formulation (IR). The effect of food on the pharmacokinetics of CR sarpogrelate was also evaluated.

Comparison of clinical outcomes between culprit vessel only and multivessel percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel coronary diseases

Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction (STEMI) patients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention (PPCI) were analyzed. We used propensity score matching (PSM) to control differences of baseline characteristics between culprit only intervention (CP) and multivessel percutaneous coronary interventions (MP), and between double vessel disease (DVD) and triple vessel disease (TVD). The major adverse cardiac event (MACE) was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE (14.2% vs. 8.6%, P = 0.01), any cause of revascularization (10.6% vs. 5.9%, P = 0.01), and repeated PCI (9.5% vs. 5.7%, P = 0.02), as compared to DVD patients during one year after discharge. MP reduced MACE effectively (7.3% vs. 13.8%, P = 0.03), as compared to CP for one year, but all cause of death (1.6% vs. 3.2%, P = 0.38), MI (0.4% vs. 0.8%, P = 1.00), and any cause of revascularization (5.3% vs. 9.7%, P = 0.09) were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD. MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.

Periprocedural myocardial infarction after retrograde approach for chronic total occlusion of coronary artery: demonstrated by cardiac magnetic resonance imaging.

A retrograde approach through the collateral channels was recently proposed as one of the most promising current techniques for percutaneous coronary intervention of chronic total occlusion in coronary arteries (CTO). This report describes the case of a 68-year-old man in whom CTO was successfully crossed with a wire by the retrograde approach using septal collateral, but the patient suffered from a complication with septal myocardial infarction demonstrated by cardiac magnetic resonance imaging.