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1.  Abnormal left ventricular longitudinal functional reserve in patients with diabetes mellitus: implication for detecting subclinical myocardial dysfunction using exercise tissue Doppler echocardiography 
Heart  2007;93(12):1571-1576.
Background
Sublinical myocardial dysfunction occurs in a significant number of patients with type 2 diabetes. Assessment of ventricular long‐axis function by measuring mitral annular velocities using tissue Doppler echocardiography (TDE) is thought to provide a more sensitive index of systolic and diastolic function. We hypothesised that augmentation of left ventricular (LV) longitudinal contraction and relaxation during exercise would be blunted in patients with type 2 diabetes.
Methods
Mitral annular systolic (S′) and early diastolic (E′) velocities were measured at rest and during supine bicycle exercise (25 W, 3 min increments) in 53 patients (27 male, mean age 53±14 years) with type 2 diabetes and 53 subjects with age and gender‐matched control. None had echocardiographic evidence of resting or inducible myocardial ischaemia.
Results
There were no significant differences in mitral inflow velocities at rest between the two groups. E′ and S′ at rest were also similar between the groups. However, S′ (7.1±1.3 vs 8.3±1.8 cm/s at 25 W, p = 0.0021; 8.1±1.5 vs 9.1±2.0 cm/s at 50 W, p = 0.026) and E′ (8.5±2.3 vs 9.9±3.1 cm/s at 25 W, p = 0.054; 9.1±2.1 vs 10.9±2.5 cm/s at 50 W, p = 0.0093) during exercise were significantly lower in patients with diabetes compared with controls. Longitudinal systolic and diastolic function reserve indices were significantly lower in patients with diabetes compared with that of controls (systolic index, 0.6±0.70 vs 1.2±1.5 cm/s at 25 W, p = 0.029; 1.2±1.2 vs 2.1±1.6 cm/s at 50 W, p = 0.009; diastolic index, 1.9±1.2 vs 2.5±2.2 cm/s at 25 W, p = 0.07; 2.3±1.3 vs 3.2±2.2 cm/s at 50 W, p = 0.031).
Conclusion
In conclusion, unlike resting mitral inflow and annular velocities, changes of systolic and diastolic velocities of the mitral annulus during exercise were significantly reduced in patients with type 2 diabetes compared with the control group. The assessment of LV longitudinal functional reserve with exercise using TDE appears to be helpful in identifying early myocardial dysfunction in patients with type 2 diabetes.
doi:10.1136/hrt.2006.101667
PMCID: PMC2095774  PMID: 17449503
2.  Relationship Between Serum Biochemical Markers of Myocardial Fibrosis and Diastolic Function at Rest and With Exercise in Hypertrophic Cardiomyopathy 
Korean Circulation Journal  2009;39(12):519-524.
Background and Objectives
Recent studies have demonstrated the usefulness of biochemical markers of collagen turnover as markers of myocardial fibrosis in various diseases. In this study, we hypothesized that increased collagen markers in patients with hypertrophic cardiomyopathy (HCM) were correlated with diastolic function at rest and diastolic functional reserve during exercise.
Subjects and Methods
Thirty-six patients with HCM and 21 controls with normal left ventricular thickness were studied. Mitral septal annular velocities and mitral inflow velocities were measured at rest and during graded supine bicycle exercise (25 W, 3-minute increments) for the assessment of diastolic function at rest and during exercise. By radioimmunoassay, a byproduct of collagen III synthesis (PIIINP) and peptides resulting from collagen I synthesis (PINP) and degradation (ICTP) were measured. The patients with HCM were divided into two groups according to the median value of the PINP/ICTP ratio in the group.
Results
At rest, the mitral annular early diastolic velocity (E') was lower and the E/E' was higher in the patients with HCM with high a PINP/ICTP ratio compared with patients with HCM with a low PINP/ICTP ratio and controls (p<0.001, p=0.012). With exercise, the Doppler parameters were increased in all groups, but there was no significant difference in the change in E' and E/E' during exercise according to collagen turnover markers.
Conclusion
A higher PINP/ICTP ratio was associated with resting diastolic dysfunction in patients with HCM; however, there was no relationship with augmented diastolic dysfunction during exercise. We suggest that the type I collagen synthesis-to-degradation ratio is a useful marker of resting diastolic function in patients with HCM.
doi:10.4070/kcj.2009.39.12.519
PMCID: PMC2801459  PMID: 20049137
Cardiomyopathy hypertrophic; Collagen; Myocardial contraction, diastole; Exercise
3.  Therapeutic Strategies for Diastolic Dysfunction: A Clinical Perspective 
Diastolic dysfunction, which is increasingly viewed as being influential in precipitating heart failure and determining prognosis, is often unrecognized and has therapeutic implications distinct from those that occur with systolic dysfunction. In this review, several therapeutic modalities including pharmacologic, nonpharmacologic, and surgical approaches for primary diastolic dysfunction and heart failure will be discussed.
doi:10.4250/jcu.2009.17.3.86
PMCID: PMC2889378  PMID: 20661322
Diastolic dysfunction; Therapy
4.  Serial Assessment of Myocardial Properties Using Cyclic Variation of Integrated Backscatter in an Adriamycin-Induced Cardiomyopathy Rat Model 
Yonsei Medical Journal  2005;46(1):73-77.
Although adriamycin (Doxorubicin) is one of the most effective and useful antineoplastic agents for the treatment of a variety of malignancies, its repeated administration can induce irreversible myocardial damage and resultant heart failure. Currently, no marker to detect early cardiac damage is available. The purpose of this study was to investigate whether an assessment of the acoustic properties of the myocardium could enable the earlier detection of myocardial damage after adriamycin chemotherapy. Forty Wistar rats were treated with adriamycin (2 mg/kg, i.v.) once a week for 2, 4, 6 or 8 weeks consecutively. Left ventricular ejection fraction (LVEF) was calculated using M-mode echocardiography data. The magnitude of cardiac cycle dependent variation of integrated backscatter (CVIB) of the myocardium was measured in the mid segment of the septum and in the posterior wall of the left ventricle, using a real time two dimensional integrated backscatter imaging system. LVEF was significantly lower in the adriamycin-treated 8-week group than in the controls (75 ± 9 vs 57 ± 8%, p < 0.05). Myocyte damage was only seen in the 8-week adriamycin-treated group. However, no significant changes of CVIB were observed between baseline or during follow-up in the ADR or control group. In conclusion, serial assessment of the acoustic properties of the myocardium may not be an optimal tool for the early detection of myocardial damage after doxorubicin chemotherapy in a rat model.
doi:10.3349/ymj.2005.46.1.73
PMCID: PMC2823060  PMID: 15744808
Anthracycline; cardiotoxicity; echocardiography
5.  Prosthesis-Patient Mismatch after Mitral Valve Replacement: Comparison of Different Methods of Effective Orifice Area Calculation 
Yonsei Medical Journal  2016;57(2):328-336.
Purpose
The incidence of prosthesis-patient mismatch (PPM) after mitral valve replacement (MVR) has been reported to vary. The purpose of the current study was to investigate incidence of PPM according to the different methods of calculating effective orifice area (EOA), including the continuity equation (CE), pressure half time (PHT) method and use of reference EOA, and to compare these with various echocardiographic variables.
Materials and Methods
We retrospectively reviewed 166 individuals who received isolated MVR due to rheumatic mitral stenosis and had postoperative echocardiography performed between 12 and 60 months after MVR. EOA was determined by CE (EOACE) and PHT using Doppler echocardiography. Reference EOA was determined from the literature or values offered by the manufacturer. Indexed EOA was used to define PPM as present if ≤1.2 cm2/m2.
Results
Prevalence of PPM was different depending on the methods used to calculate EOA, ranging from 7% in PHT method to 49% in referred EOA method to 62% in CE methods. The intraclass correlation coefficient was low between the methods. PPM was associated with raised trans-prosthetic pressure, only when calculated by CE (p=0.021). Indexed EOACE was the only predictor of postoperative systolic pulmonary artery (PA) pressure, even after adjusting for age, preoperative systolic PA pressure and postoperative left atrial volume index (p<0.001).
Conclusion
Prevalence of mitral PPM varied according to the methods used to calculate EOA in patients with mitral stenosis after MVR. Among the various methods used to define PPM, EOACE was the only predictor of postoperative hemodynamic parameters.
doi:10.3349/ymj.2016.57.2.328
PMCID: PMC4740523  PMID: 26847283
Mitral valve; heart valve prosthesis
6.  Differential Impact of Constrictive Physiology after Pericardiocentesis in Malignancy Patients with Pericardial Effusion 
PLoS ONE  2015;10(12):e0145461.
Background
Echocardiographic signs of constrictive physiology (CP) after pericardiocentesis are frequently observed in malignancy patients. The purpose of the current study was to explore whether features of CP after pericardiocentesis have prognostic impact in malignancy patients with pericardial effusion (PE).
Methods
We retrospectively reviewed 467 consecutive patients who underwent pericardiocentesis at our institution from January 2006 to May 2014. Among them, 205 patients with advanced malignancy who underwent comprehensive echocardiography after the procedure comprised the study population. Co-primary end points were all-cause mortality (ACM) and repeated drainage (RD) for PE. Patients were divided into four subgroups according to cytologic result for malignant cells and CP (positive cytology with negative CP, both positive, both negative, and negative cytology with positive CP).
Results
CP after pericardiocentesis was present in 106 patients (50%) at median 4 days after the procedure. During median follow-up of 208 days, ACM and RD occurred in 162 patients (79%) and 29 patients (14%), respectively. Cox regression analysis revealed that independent predictors for ACM were male gender and positive cytology (all, p < 0.05). For RD, predictors were positive cytology, the absence of cardiac tamponade, and negative CP after pericardiocentesis (all, p < 0.05). When the patients were divided into four subgroups, patients with negative cytology and positive CP demonstrated the most favorable survival (hazard ratio [HR]: 0.39, p = 0.005) and the lowest RD rates (HR: 0.07, p = 0.012).
Conclusion
CP after pericardiocentesis is common, but does not always imply poor survival or the need for RD in patients with advanced malignancies. On the contrary, the presence of CP in patients with negative cytology conferred the most favorable survival and the lowest rate of RD. Comprehensive echocardiographic evaluation for CP after pericardiocentesis would be helpful for predicting prognosis in patients with advanced malignancies.
doi:10.1371/journal.pone.0145461
PMCID: PMC4686385  PMID: 26691279
7.  Non-invasive assessment of vascular alteration using ultrasound 
Clinical Hypertension  2015;21:25.
It is well known that arterial function relates to cardiovascular morbidity and mortality. The noninvasive technology for the assessment of arterial function has developed as the importance of prevention of early cardiovascular disease has been emphasized. Over 2-D and Doppler echocardiography, speckle-tracking echocardiography has emerged as a valuable ultrasound imaging technique that allows for an objective and quantitative evaluation of global and regional myocardial function. Recently, several studies have extended its applicability beyond cardiac chambers, such as artery. Measurement of carotid arterial strain with speckle tracking ultrasound has been shown to be feasible and reliable. This review describes the new ultrasound techniques to assess arterial function and their clinical implications.
doi:10.1186/s40885-015-0035-4
PMCID: PMC4750810  PMID: 26893935
Arterial function; Carotid artery; Ultrasound
9.  Relationship between Myocardial Extracellular Space Expansion Estimated with Post-Contrast T1 Mapping MRI and Left Ventricular Remodeling and Neurohormonal Activation in Patients with Dilated Cardiomyopathy 
Korean Journal of Radiology  2015;16(5):1153-1162.
Objective
Post-contrast T1 values are closely related to the degree of myocardial extracellular space expansion. We determined the relationship between post-contrast T1 values and left ventricular (LV) diastolic function, LV remodeling, and neurohormonal activation in patients with dilated cardiomyopathy (DCM).
Materials and Methods
Fifty-nine patients with DCM (mean age, 55 ± 15 years; 41 males and 18 females) who underwent both 1.5T magnetic resonance imaging and echocardiography were enrolled. The post-contrast 10-minute T1 value was generated from inversion time scout images obtained using the Look-Locker inversion recovery sequence and a curve-fitting algorithm. The T1 sample volume was obtained from three interventricular septal points, and the mean T1 value was used for analysis. The N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level was measured in 40 patients.
Results
The mean LV ejection fraction was 24 ± 9% and the post-T1 value was 254.5 ± 46.4 ms. The post-contrast T1 value was significantly correlated with systolic longitudinal septal velocity (s'), peak late diastolic velocity of the mitral annulus (a'), the diastolic elastance index (Ed, [E/e']/stroke volume), LV mass/volume ratio, LV end-diastolic wall stress, and LV end-systolic wall stress. In a multivariate analysis without NT-proBNP, T1 values were independently correlated with Ed (β = -0.351, p = 0.016) and the LV mass/volume ratio (β = 0.495, p = 0.001). When NT-proBNP was used in the analysis, NT-proBNP was independently correlated with the T1 values (β = -0.339, p = 0.017).
Conclusion
Post-contrast T1 is closely related to LV remodeling, diastolic function, and neurohormonal activation in patients with DCM.
doi:10.3348/kjr.2015.16.5.1153
PMCID: PMC4559787  PMID: 26355278
Dilated cardiomyopathy; T1 mapping; Diastolic function
10.  Automated quantification of left atrial size using three-beat averaging real-time three dimensional Echocardiography in patients with atrial fibrillation 
Background
Left atrial (LA) sizing in patients with atrial fibrillation (AF) is crucial for follow-up and outcome. Recently, the automated quantification of LA using the novel three-beat averaging real-time three dimensional echocardiography (3BA-RT3DE) is introduced. The aim of this study was to assess the feasibility and accuracy of 3BA-RT3DE in patients with atrial fibrillation (AF).
Methods
Thirty-one patients with AF (62.8 ± 11.7 years, 67.7 % male) were prospectively recruited to have two dimensional echocardiography (2DE) and 3BA-RT3DE (SC 2000, ACUSON, USA). The maximal left atrial (LA) volume was measured by the conventional prolate-ellipse (PE) and area-length (AL) method using three-beat averaging 2D transthoracic echocardiography and automated software analysis (eSie volume analysis, Siemens Medical Solution, Mountain view, USA); measurements were compared with those obtained by computed tomography (CT).
Results
Maximal LA volume by 3BA-RT3DE was feasible for all patients. LA volume was 68.4 ± 28.2 by PE-2DE, 89.2 ± 33.1 by AL-2DE, 100.6 ± 31.8 by 3BA-RT3DE, and 131.2 ± 42.2 mL by CT. LA volume from PE-2DE (R2 = 0.48, p < 0.001, ICC = 0.64, p < 0.001), AL-2DE (R2 = 0.47, p < 0.001, ICC = 0.67, p < 0.001), and 3BA-RT3DE (R2 = 0.50, p = 0.001, ICC = 0.65, p < 0.001) showed significant correlations with CT. However, 3BA-RT3DE demonstrated a small degree of underestimation (30.5 mL) of LA volume compared to 2DE-based measurements. Good-quality images from 3BA-RT3DE (n = 16) showed a significantly tighter correlation with images from CT scanning (R2 = 0.60, p = 0.0004, ICC = 0.76, p < 0.001) compared to those of fair quality.
Conclusion
Automated quantification of LA volume using 3BA-RT3DE is feasible and accurate in patients with AF. An image of good quality is essential for maximizing the value of this method in clinical practice.
doi:10.1186/s12947-015-0032-5
PMCID: PMC4548448  PMID: 26306693
Three-dimensional echocardiography; Left atrial volume; Atrial fibrillation
11.  Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction 
Cellular and Molecular Immunology  2014;12(4):466-473.
Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction (MI). We studied the immunological characteristics and clinical impact of CD8+CD57+ T cells in acute MI patients. The frequency of CD57+ cells among CD8+ T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57+ cells in the CD8+ T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8+CD57+ T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8+CD57+ T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8+CD57+ T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8+ T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8+ T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.
doi:10.1038/cmi.2014.74
PMCID: PMC4496543  PMID: 25152079
acute myocardial infarction; CD8+CD57+ T cells; immunosenescence
12.  Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy 
Background
The study reported here compared the blood pressure (BP)-lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide (HCTZ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60 mg.
Methods
Patients with sitting diastolic blood pressure (siDBP) ≥90 mmHg with 4 weeks of once-daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg.
Results
Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 (6.88±8.10 mmHg vs 3.38±7.33, P=0.0008), and the effect persisted at Week 8 (8.67±9.39 mmHg vs 5.02±8.27 mmHg, P=0.0023). Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week 4, 10.50±13.76 mmHg vs 5.75±12.18 mmHg, P=0.0069 and, at Week 8, 13.45±15.15 mmHg vs 6.84±13.57 mmHg, P=0.0007). The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP <90 mmHg after 4 weeks of treatment was higher in the fimasartan/HCTZ treatment group than in the fimasartan treatment group (53.6% vs 39.8%, P=0.0359). The overall incidence of adverse drug reaction was 11.79% with no significant difference between the treatment groups.
Conclusion
The combination treatment of fimasartan and HCTZ achieved better BP control than fimasartan monotherapy, and had comparable safety and tolerance to fimasartan monotherapy.
doi:10.2147/DDDT.S82098
PMCID: PMC4459623  PMID: 26082615
blood pressure; antihypertensive; angiotensin-converting enzyme inhibitor; angiotensin-receptor blocker; angiotensin II type 1 receptor; renin–angiotensin–aldosterone system inhibitor
13.  Clinical hypertension: a new era 
We are delighted to announce the launch of the new journal Clinical Hypertension. Clinical Hypertension is an open-access, peer-reviewed, online journal, which will publish scientific investigation of the highest quality in the field of blood pressure regulation and pathophysiology, treatment, and prevention of hypertension. The editors encourage the submission of original articles that deal with basic, clinical, and population studies of hypertension and related fields, such as cardiology, nephrology, endocrinology, neuroscience, vascular biology, physiology, pharmacology, cellular and molecular biology, and genetics.
doi:10.1186/2056-5909-20-7
PMCID: PMC4743856  PMID: 26893912
14.  Safety and Cost-Effectiveness of Bridge Therapies for Invasive Dental Procedures in Patients with Mechanical Heart Valves 
Yonsei Medical Journal  2014;55(4):937-943.
Purpose
Bridge anticoagulation therapy is mostly utilized in patients with mechanical heart valves (MHV) receiving warfarin therapy during invasive dental procedures because of the risk of excessive bleeding related to highly vascular supporting dental structures. Bridge therapy using low molecular weight heparin may be an attractive option for invasive dental procedures; however, its safety and cost-effectiveness compared with unfractionated heparin (UFH) is uncertain.
Materials and Methods
This study investigated the safety and cost-effectiveness of enoxaparin in comparison to UFH for bridge therapy in 165 consecutive patients (57±11 years, 35% men) with MHV who underwent invasive dental procedures.
Results
This study included 75 patients treated with UFH-based bridge therapy (45%) and 90 patients treated with enoxaparin-based bridge therapy (55%). The bleeding risk of dental procedures and the incidence of clinical adverse outcomes were not significantly different between the UFH group and the enoxaparin group. However, total medical costs were significantly lower in the enoxaparin group than in the UFH group (p<0.001). After multivariate adjustment, old age (≥65 years) was significantly associated with an increased risk of total bleeding independent of bridging methods (odds ratio, 2.51; 95% confidence interval, 1.15-5.48; p=0.022). Enoxaparin-based bridge therapy (β=-0.694, p<0.001) and major bleeding (β=0.296, p=0.045) were significantly associated with the medical costs within 30 days after dental procedures.
Conclusion
Considering the benefit of enoxaparin in cost-effectiveness, enoxaparin may be more efficient than UFH for bridge therapy in patients with MHV who required invasive dental procedures.
doi:10.3349/ymj.2014.55.4.937
PMCID: PMC4075397  PMID: 24954321
Anticoagulation; bridge therapy; dental procedure; low molecular weight heparin; mechanical heart valve
15.  Combination of a peroxisome proliferator‐activated receptor‐gamma agonist and an angiotensin II receptor blocker attenuates myocardial fibrosis and dysfunction in type 2 diabetic rats 
Abstract
Aims/Introduction
We aimed to examine the effect of an angiotensin II receptor blocker (ARB), a peroxisome proliferator‐activated receptor (PPAR)‐gamma agonist, and their combination on myocardial fibrosis and function in type 2 diabetic rats.
Materials and Methods
Five male Long‐Evans Tokushima Otsuka (LETO) rats and 20 male Otsuka Long‐Evans Tokushima Fatty (OLETF) rats were used. OLETF rats were assigned to four groups (n = 5 per group) at 28 weeks‐of‐age: untreated, losartan‐treated, rosiglitazone‐treated and combination‐treated. The ARB, losartan, was administered at a dose of 5 mg/kg/day, and the PPAR‐gamma agonist, rosiglitazone, was administered at a dose of 3 mg/kg/day by oral gavage for 12 weeks. Urine and blood samples were collected, and two‐dimensional echocardiograms and strain rate imaging were obtained at 28 and 40 weeks. Cytokines were evaluated by reverse transcriptase polymerase chain reaction, and histological analysis was carried out at 40 weeks.
Results
At 40 weeks, the global radial strains of the losartan‐treated (55.7 ± 4.5%, P = 0.021) and combination‐treated groups (59.3 ± 6.7%, P = 0.001) were significantly higher compared with the untreated OLETFs (44.3 ± 10.5%). No difference was observed when compared with LETO rats. Although the rosiglitazone‐treated group showed a better metabolic profile than the untreated OLETF group, there was no difference in the global radial strain (49.8 ± 6.0 vs 44.3 ± 10.5, P = 0.402). The expression of pro‐inflammatory cytokines, and collagen type I and III were consistently attenuated in the losartan‐treated and combination‐treated OLETF groups, but not in the rosiglitazone‐treated group.
Conclusions
A combination of rosiglitazone and losartan attenuates myocardial fibrosis and dysfunction in type 2 diabetic rats.
doi:10.1111/jdi.12153
PMCID: PMC4210065  PMID: 25411595
Angiotensin II receptor blocker; Diabetic cardiomyopathy; Peroxisome proliferator‐activated receptor‐gamma agonist
16.  Soluble CD93 Levels in Patients with Acute Myocardial Infarction and Its Implication on Clinical Outcome 
PLoS ONE  2014;9(5):e96538.
Background
Inflammation plays a key role in the pathogenesis of acute myocardial infarction (MI). However, it is unclear whether marker of immune activation will provide prognostic information in these patients. We hypothesized that circulating levels of soluble CD93 (sCD93), a soluble form of transmembrane glycoprotein CD93, is increased in acute MI patients and its level would be associated with clinical outcomes in patients with acute MI.
Methods
We measured circulating levels of sCD93 in 120 patients with acute MI (63±13 yrs, M∶F = 85∶35) and in 120 age, sex-matched control subjects. In patients with acute MI, clinical characteristics, echocardiographic and laboratory findings were assessed at the time of initial enrollment. The primary outcome was defined as all-cause and cardiovascular death.
Results
Circulating sCD93 levels were significantly higher in patients with acute MI than in control subjects (552.1±293.7 vs. 429.8±114.2 ng/mL, p<0.0001). Upon in vitro inflammatory stimulation, increased CD93 shedding was demonstrated in acute MI patients but not in control subjects. During follow up period (median 208 days, 3-1058 days), the primary outcome occurred in 18 (15%) patients (9 cardiovascular deaths). Circulating levels of sCD93 were associated with all cause (p<0.0001) and cardiovascular (p<0.0001) mortality in patients with acute MI. Multivariate Cox regression analysis revealed that initial sCD93 level was found to be an independent predictor of all cause (p = 0.002) and cardiovascular mortality (p = 0.033) when controlled for age and left ventricular ejection fraction.
Conclusions
Circulating levels of sCD93 are elevated in patients with acute MI and their levels were associated with adverse clinical outcomes.
doi:10.1371/journal.pone.0096538
PMCID: PMC4011875  PMID: 24801400
17.  The Case of Isolated Double Atrial Septum with Persistent Interatrial Space 
Double atrial septum is very rare atrial septal malformation which has double layered atrial septum with persistent interatrial space between the two atria. Clinically, most cases of this anomaly are asymptomatic unless manifest as thromboembolic complications, such as stroke, or transient ischemic attack, that thrombus may be originated from this interatrial space. We report a case of a 69-year-old man who was diagnosed with isolated double atrial septum by transthoracic echocardiography.
doi:10.4250/jcu.2013.21.4.197
PMCID: PMC3894374  PMID: 24459570
Double atrial septum; Interatrial space
18.  Prediction of Hemorrhagic Transformation Following Embolic Stroke in Patients with Prosthetic Valve Endocarditis 
Background
Hemorrhagic transformation (HT) of stroke is a disastrous complication in patients with infective endocarditis (IE). In patients with mechanical heart valves complicated by IE, physicians struggle with the appropriateness of anticoagulation administration given the risk of thromboembolism and HT of stroke. In this study, we aimed to define predictive parameters of HT of stroke in patients with prosthetic valve endocarditis (PVE).
Methods
This study was a multicenter, retrospective design. We recruited from 7 institutions a total of 111 patients diagnosed with PVE during May, 2011 to April, 2012.
Results
Complication of stroke was seen in 26/111 patients (23%), and HT of stroke was seen in 11/111 patients (10%). Most patients with HT (9/11, 82%) had supratherapeutic prothrombin times. However, there were no significant differences in clinical and laboratory values between PVE patients without stroke and those patients who had a stroke and with or without concurrent HT. Furthermore, echocardiographic parameters also did not show significant between-group differences.
Conclusion
Even though this was a multicenter study, a limited number of patients was identified and may explain the negative results seen here. However, a large number of PVE patients with stroke also developed HT. Therefore, further studies to define predictive parameters of HT should be implemented in a larger population.
doi:10.4250/jcu.2013.21.3.123
PMCID: PMC3816162  PMID: 24198918
Infective endocarditis; Embolization; Hemorrhagic stroke
19.  Prosthetic Mitral Valve Leaflet Escape 
Leaflet escape of prosthetic valve is rare but potentially life threatening. It is essential to make timely diagnosis in order to avoid mortality. Transesophageal echocardiography and cinefluoroscopy is usually diagnostic and the location of the missing leaflet can be identified by computed tomography (CT). Emergent surgical correction is mandatory. We report a case of fractured escape of Edward-Duromedics mitral valve 27 years after the surgery. The patient presented with symptoms of acute decompensated heart failure and cardiogenic shock. She was instantly intubated and mechanically ventilated. After prompt evaluation including transthoracic echocardiography and CT, the escape of the leaflet was confirmed. The patient underwent emergent surgery for replacement of the damaged prosthetic valves immediately. Eleven days after the surgery, the dislodged leaflet in iliac artery was removed safely and the patient recovered well.
doi:10.4250/jcu.2013.21.2.96
PMCID: PMC3701786  PMID: 23837121
Cardiac valve prosthesis; Prosthesis failure; Cardiogenic shock
21.  Incidence of post-transplant glomerulonephritis and its impact on graft outcome 
Background
Herein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN.
Methods
Among the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study.
Results
The incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors.
Conclusion
We conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or de novo GN should be the critical focus of post-transplant care.
doi:10.1016/j.krcp.2012.09.004
PMCID: PMC4716107  PMID: 26889425
Glomerulonephritis; Graft survival; Kidney transplantation; Risk factors
22.  Visceral Obesity of the Heart: Extensive Lipomatous Hypertrophy of Interatrial Septum 
doi:10.4250/jcu.2012.20.3.161
PMCID: PMC3498316  PMID: 23185662
Obesity; Lipomatous hypertrophy; Cardiac imaging
23.  Serial Plasma Levels of Angiogenic Factors in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention 
Korean Circulation Journal  2012;42(7):464-470.
Background and Objectives
Patients with acute myocardial infarction show varying degrees of collateral development. However, the relationships between angiogenic factors and degree of collaterals are not well known.
Subjects and Methods
Fifty-nine patients (mean age, 59±10 years) with ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Patients were divided into one of 2 groups: group I (Rentrop collateral grade 0/1, n=34) or group II (grade 2/3, n=25). Plasma levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sFlt-1), angiopoietin (Ang)-2, and soluble Tie-2 at baseline, 24 and 48 hours after PCI were measured.
Results
There were fewer diabetic patients and higher incidence of previous angina and multi-vessel disease in group II. Group II had a lower left ventricular ejection fraction and a trend toward longer pain-to-balloon time. Plasma levels of Ang-2, sFlt-1 were elevated prior to primary PCI and decreased after PCI, whereas plasma level of VEGF was relatively low initially, however rose after PCI. sTie-2 levels showed no significant interval change in group I, but decreased over time in group II. VEGF, sFlt-1, and Tie-2 levels did not differ between the groups at each time point. However, plasma levels of Ang-2 were higher in group I than in group II at baseline and at 48 hours.
Conclusion
Presence of collaterals in STEMI patients undergoing primary PCI was associated with lesser rise in Ang-2 plasma level. VEGF showed a delayed response to acute ischemia compared to Ang-2. Clinical implications of our findings need to be investigated in further studies.
doi:10.4070/kcj.2012.42.7.464
PMCID: PMC3409395  PMID: 22870080
Myocardial infarction; Angiogenesis modulating agents; Vascular endothelial growth factor; Angiopoietin-2
24.  Prediction of Left Atrial Fibrosis With Speckle Tracking Echocardiography in Mitral Valve Disease: A Comparative Study With Histopathology 
Korean Circulation Journal  2012;42(5):311-318.
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.
doi:10.4070/kcj.2012.42.5.311
PMCID: PMC3369962  PMID: 22701133
Echocardiography; Fibrosis; Left atrium
25.  Hemorrhagic Transformation of Ischemic Stroke: Severe Complications of Prosthetic Valve Endocarditis 
Korean Circulation Journal  2011;41(8):490-493.
Ischemic stroke is a common complication of infective endocarditis (IE), occurring in 20-40% of left side IE cases. In these subsets, anticoagulation therapy may provoke hemorrhagic transformation (HT) of ischemic stroke, and complications of this magnitude deteriorate the clinical course for IE patients. However, in cases of IE complicated with a mechanical prosthetic valve, the physician can be concerned over the maintenance of anticoagulation due to the risk of thrombotic complication. According to our retrospective review, HT of ischemic stroke in prosthetic valve endocarditis occurred 13.8% (4/29) of the time in a variety of situations. Some of these even arose in patients with a subtherapeutic range of prothrombin time.
doi:10.4070/kcj.2011.41.8.490
PMCID: PMC3173673  PMID: 21949537
Heart valve prosthesis; Endocarditis; Stroke; Cerebral hemorrhage; Anticoagulants

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