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1.  Differential association between obesity and coronary artery disease according to the presence of diabetes in a Korean population 
Background
Coronary artery disease (CAD) is a major cardiovascular complication in diabetic patients. Despite the significant association between obesity and diabetes, the majority of the diabetic subjects are not obese in an Asian population. This study evaluated the association between obesity and coronary artery disease (CAD) according to the diabetes status in a Korean population.
Methods
The association between obesity and CAD using the parameters of any plaque, obstructive plaque, and coronary artery calcium score (CACS) >100 according to the presence of diabetes was evaluated in 7,234 Korean adults who underwent multi-detector computed tomography for general health evaluations. Obesity was defined as a body mass index (BMI) ≥25 kg/m2.
Results
The prevalence of obesity was significantly higher in diabetic subjects than in non-diabetic subjects, but the majority of the diabetic subjects were non-obese (48% vs. 37%, p <0.001). The incidence of any plaque (58% vs. 29%), obstructive plaque (20% vs. 6%), and CACS >100 (20% vs. 6%) were significantly higher in diabetic patients than in non-diabetic subjects (p <0.001, respectively). Incidence of any plaque (33% vs. 26%, p <0.001), obstructive plaque (7% vs. 6%, p = 0.014), and CACS >100 (8% vs. 6%, p = 0.002) was significantly higher in non-diabetic subjects with obesity than in those without obesity, but the incidence of all coronary parameters was not different in diabetic subjects according to the obesity status. After adjusting for confounding risk factors including age, gender, hypertension, dyslipidemia, current smoking, and mild renal dysfunction, obesity was independently associated with increased risks of any plaque (OR 1.14) and CACS >100 (OR 1.31) only in non-diabetic subjects (p <0.05, respectively). Multiple logistic regression models revealed that diabetes was independently associated with all coronary parameters.
Conclusion
Despite a significantly higher prevalence of obesity in diabetic subjects than in non-diabetic subjects, obesity is associated with the presence of any plaque and severe coronary calcification only in subjects without established diabetes among Korean population.
doi:10.1186/1758-5996-6-134
PMCID: PMC4271324  PMID: 25530810
Obesity; Diabetes; Coronary artery disease; Cardiac computed tomographic angiography
2.  Late Gadolinium Enhancement in Cardiac MRI in Patients with Severe Aortic Stenosis and Preserved Left Ventricular Systolic Function Is Related to Attenuated Improvement of Left Ventricular Geometry and Filling Pressure after Aortic Valve Replacement 
Korean Circulation Journal  2014;44(5):312-319.
Background and Objectives
We investigated echocardiographic predictors: left ventricular (LV) geometric changes following aortic valve replacement (AVR) according to the late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) in patients with severe aortic stenosis (AS) and preserved LV systolic function.
Subjects and Methods
We analyzed 41 patients (24 males, 63.1±8.7 years) with preserved LV systolic function who were scheduled to undergo AVR for severe AS. All patients were examined with transthoracic echocardiography (TTE), CMR before and after AVR (in the hospital) and serial TTEs (at 6 and 12 months) were repeated.
Results
The group with LGE (LGE+) showed greater wall thickness (septum, 14.3±2.6 mm vs. 11.5±2.0 mm, p=0.001, posterior; 14.3±2.5 mm vs. 11.4±1.6 mm, p<0.001), lower tissue Doppler image (TDIS', 4.4±1.4 cm/s vs. 5.5±1.2 cm/s, p=0.021; TDI E', 3.2±0.9 cm/s vs. 4.8±1.4 cm/s, p=0.002), and greater E/e' (21.8±10.3 vs. 15.4±6.3, p=0.066) than those without LGE (LGE-). Multivariate analysis show that TDI e' (odds ratio=0.078, 95% confidence interval=0.007-0.888, p=0.040) was an independent determinant of LGE+. In an analysis of the 6- and 12-month follow-up compared with pre-AVR, LGE- showed decreased LV end-diastolic diameter (48.3±5.0 mm vs. 45.8±3.6 mm, p=0.027; 48.3±5.0 mm vs. 46.5±3.4 mm, p=0.019). Moreover, E/e' (at 12 months) showed further improved LV filling pressure (16.0±6.6 vs. 12.3±4.3, p=0.001) compared with pre-AVR. However, LGE+ showed no significant improvement.
Conclusion
The absence of LGE is associated with favorable improvements in LV geometry and filling pressure. TDI E' is an independent determinant of LGE in patients with severe AS and preserved LV systolic function.
doi:10.4070/kcj.2014.44.5.312
PMCID: PMC4180608  PMID: 25278984
Cardiac magnetic resonance imaging; Echocardiography; Aortic stenosis; Late gadolinium enhancement
3.  Differential association between metabolic syndrome and coronary artery disease evaluated with cardiac computed tomography according to the presence of diabetes in a symptomatic Korean population 
Background
Metabolic syndrome (MetS) is associated with increased risks of diabetes and coronary artery disease (CAD). Despite the controversial inclusion of established diabetes in MetS, the association between MetS and CAD according to diabetes status has not been elucidated in the Asian population.
Methods
We evaluated the association between MetS and CAD using the parameters including any plaque, obstructive plaque, and coronary artery calcium score (CACS) >100 according to diabetes status in 2,869 symptomatic Korean subjects who underwent cardiac computed tomographic angiography.
Results
The prevalence of MetS was significantly higher in the diabetic subjects than in the non-diabetic subjects (69% vs. 34%, P <0.001). The incidence of any plaque (64% vs. 43%, P <0.001), obstructive plaque (26% vs. 13%, P = 0.006), and CACS >100 (23% vs. 12%, P = 0.012) was significantly higher in diabetic subjects than in non-diabetic subjects. Among the MetS components, decreased high-density lipoprotein level was significantly associated with any plaque (odds ratio [OR] 1.35), obstructive plaque (OR 1.55), and CACS >100 (OR 1.57) in the non-diabetic subjects (P <0.01, respectively). However, none of the MetS components were associated with all the parameters in the diabetic subjects. Multivariate regression analysis revealed that MetS and the number of MetS components (MetSN) were independently associated with any plaque (MetS: OR 1.55, P <0.001; MetSN: OR 1.22, P <0.001), obstructive plaque (MetS: OR 1.52, P = 0.003; MetSN: OR 1.25, P <0.001), and CACS >100 (MetS: OR 1.46, P = 0.015; MetSN: OR 1.21, P = 0.004) only in the non-diabetic subjects, respectively.
Conclusions
MetS was independently associated with the presence and severity of CAD only in the non-diabetic subjects among the symptomatic Korean population.
doi:10.1186/1471-2261-14-105
PMCID: PMC4236521  PMID: 25138993
Metabolic syndrome; Diabetes; Coronary artery disease; Coronary computed tomographic angiography
4.  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
5.  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
6.  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
7.  Arterial-Cardiac Interaction: The Concept and Implications 
Vascular stiffening of the large arteries is a common feature of human aging. Increased aortic stiffness with age may contribute to pathological changes in the left ventricle and this can induce ventricular stiffening. Vascular-ventricular stiffening combined with abnormal arterial-cardiac interaction is considered an important pathophysiology of heart failure with a preserved ejection fraction. Here, I briefly review the concept and implications of arterial-cardiac interaction and this will pave the way to understanding and controlling heart failure with a preserved ejection fraction, which is more prevalent in the elderly.
doi:10.4250/jcu.2011.19.2.62
PMCID: PMC3150697  PMID: 21860718
Aortic stiffness; Left ventricle; Heart failure
8.  Transient Right Ventricular Dysfunction After Pericardiectomy in Patients With Constrictive Pericarditis 
Korean Circulation Journal  2011;41(5):283-286.
Pericardiectomy is the standard treatment in patients with chronic constrictive pericarditis who have persistent symptoms. However, myocardial atrophy with prolonged pericardial constriction and abrupt increase in venous return can lead to heart failure with volume overload after pericardial decompression, especially in the right ventricle (RV). We experienced a 44 year old male patient who developed transient RV failure after pericardiectomy for constrictive pericarditis. Echocardiography revealed a markedly dilated RV with decreased peak systolic velocity of the tricuspid annulus, suggesting severe RV dysfunction. After treatment with inotropics and diuretics, a follow-up echocardiography revealed an improved systolic function with decreased RV chamber size. This case demonstrates the importance of volume overload and RV dysfunction in patients with constrictive pericarditis undergoing pericardiectomy.
doi:10.4070/kcj.2011.41.5.283
PMCID: PMC3116109  PMID: 21731572
Right ventricular dysfunction; Constrictive pericarditis; Pericardiectomy
9.  Aortic Aneurysm Screening in a High-Risk Population: A Non-Contrast Computed Tomography Study in Korean Males with Hypertension 
Korean Circulation Journal  2014;44(3):162-169.
Background and Objectives
Screening strategies for aortic aneurysm (AA) according to risk factors and ethnicity are controversial. This study explored the prevalence of AA and determined whether screening is necessary in a population of multiple risk factors.
Subjects and Methods
From June, 2012 to April, 2013, 542 consecutive elderly (≥65 years) male hypertensive patients without a history of AA were prospectively enrolled. After excluding 15 patients (2.8%) with aortic valve surgery, 30 patients (5.5%) with suboptimal computed tomography (CT) images, the remaining 496 patients (age 73±5 years) comprised the study population. Maximal diameters of the thoracic and abdominal aorta were measured using non-contrast CT.
Results
The prevalence of thoracic AA (TAA, diameter ≥40 mm) and abdominal AA (AAA, diameter ≥30 mm) was 36.5% (181/496) and 6.0% (30/496), respectively. In the multivariate logistic regression analysis, determinants for TAA were age {odds ratio (OR) 1.059, 95% confidence interval (CI) 1.018-1.101, p=0.005}, dyslipidemia (OR 0.621, 95% CI 0.418-0.923, p=0.018), body surface area (OR 11.92, 95% CI 2.787-50.97, p=0.001), diastolic blood pressure (OR 1.029, 95% CI 1.009-1.049, p=0.004) and AAA (OR 3.070, 95% CI 1.398-6.754, p=0.005). In contrast, AAA was independently associated with dysplipidemia (OR 2.792, 95% CI 1.091-7.143, p=0.032), current/past smokerfs (OR 4.074, 95% CI 1.160-14.31, p=0.028), and TAA (OR 3.367, 95% CI 1.550-7.313, p=0.002).
Conclusion
The prevalence of AA was significant and TAA was more prevalent than AAA in elderly Korean males with hypertension. Future research should establish distinct screening strategies for TAA and AAA according to risk factors and ethnicity.
doi:10.4070/kcj.2014.44.3.162
PMCID: PMC4037638  PMID: 24876857
Aorta; Aneurysm; Prevalence; Computed tomography
11.  Echocardiographic Investigation of the Mechanism Underlying Abnormal Interventricular Septal Motion after Open Heart Surgery 
Background
Abnormal interventricular septal motion (ASM) is frequently observed after open heart surgery (OHS). The aim of this study was to investigate the incidence and temporal change of ASM, and its underlying mechanism in patients who underwent OHS using transthoracic echocardiography (TTE).
Methods
In total, 165 patients [60 ± 13 years, 92 (56%) men] who underwent coronary bypass surgery or heart valve surgery were consecutively enrolled in a prospective manner. TTE was performed preoperatively, at 3--6-month postoperatively, and at the 1-year follow-up visit. Routine TTE images and strain analysis were performed using velocity vector imaging.
Results
ASM was documented in 121 of 165 patients (73%) immediately after surgery: 26 patients (17%) presented concomitant expiratory diastolic flow reversal of the hepatic vein, 11 (7%) had inferior vena cava plethora, and 11 (7%) had both. Only 2 patients (1%) showed clinically discernible constriction. ASM persisted 3--6 months after surgery in 38 patients (25%), but only in 23 (15%) after 1 year. There was no difference in preoperative and postoperative peak systolic strain of all segments of the left ventricle (LV) between groups with or without ASM. However, systolic radial velocity (VRad) of the mid anterior-septum and anterior wall of the LV significantly decreased in patients with ASM.
Conclusion
Although ASM was common (74%) immediately after OHS, it disappeared over time without causing clinically detectable constriction. Furthermore, we consider that ASM might not be caused by myocardial ischemia, but by the decreased systolic VRad of the interventricular septum after pericardium incision.
doi:10.4250/jcu.2014.22.1.8
PMCID: PMC3992352  PMID: 24753803
Coronary artery bypass; Valve surgery; Ventricular septum; Echocardiography
12.  Cardiovascular Molecular Imaging with Contrast Ultrasound: Principles and Applications 
Korean Circulation Journal  2014;44(1):1-9.
Methods for imaging the molecular or cellular profile of tissue are being developed for all forms of non-invasive cardiovascular imaging. It is thought that these technologies will potentially improve patient outcomes by allowing diagnosis of disease at an early-stage, monitoring disease progression, providing important information on patient risk, and for tailoring therapy to the molecular basis of disease. Molecular imaging is also already assuming an important role in science by providing a better understanding of the molecular basis of cardiovascular pathology, for assessing response to new therapies, and for rapidly optimizing new or established therapies. Ultrasound-based molecular imaging is one of these new approaches. Contrast-enhanced ultrasound molecular imaging relies on the detection of novel site-targeted microbubbles (MB) or other acoustically active particles which are administered by intravenous injection, circulate throughout the vascular compartment, and are then retained and imaged within regions of disease by ligand-directed binding. The technique is thought to be advantageous in practical terms of cost, time, and ease of use. The aim of this review is to discuss the molecular participants of cardiovascular disease that have been targeted for ultrasound imaging, general features of site-targeted MB, imaging protocols, and potential roles of ultrasound molecular imaging in cardiovascular research and clinical medicine.
doi:10.4070/kcj.2014.44.1.1
PMCID: PMC3905109  PMID: 24497883
Molecular imaging; Contrast ultrasound; Microbubbles
13.  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
14.  Automated Quantification of Mitral Regurgitation by Three Dimensional Real Time Full Volume Color Doppler Transthoracic Echocardiography: A Validation with Cardiac Magnetic Resonance Imaging and Comparison with Two Dimensional Quantitative Methods 
Background
Accurate assessment of mitral regurgitation (MR) severity is crucial for clinical decision-making and optimizing patient outcomes. Recent advances in real-time three dimensional (3D) echocardiography provide the option of real-time full volume color Doppler echocardiography (FVCD) measurements. This makes it practical to quantify MR by subtracting aortic stroke volume from the volume of mitral inflow in an automated manner.
Methods
Thirty-two patients with more than a moderate degree of MR assessed by transthoracic echocardiography (TTE) were consecutively enrolled during this study. MR volume was measured by 1) two dimensional (2D) Doppler TTE, using the proximal isovelocity surface area (PISA) and the volumetric quantification methods (VM). Then, 2) real time 3D-FVCD was subsequently obtained, and dedicated software was used to quantify the MR volume. MR volume was also measured using 3) phase contrast cardiac magnetic resonance imaging (PC-CMR). In each patient, all these measurements were obtained within the same day. Automated MR quantification was feasible in 30 of 32 patients.
Results
The mean regurgitant volume quantified by 2D-PISA, 2D-VM, 3D-FVCD, and PC-CMR was 72.1 ± 27.7, 79.9 ± 36.9, 69.9 ± 31.5, and 64.2 ± 30.7 mL, respectively (p = 0.304). There was an excellent correlation between the MR volume measured by PC-CMR and 3D-FVCD (r = 0.85, 95% CI 0.70-0.93, p < 0.001). Compared with PC-CMR, Bland-Altman analysis for 3D-FVCD showed a good agreement (2 standard deviations: 34.3 mL) than did 2D-PISA or 2D-VM (60.0 and 62.8 mL, respectively).
Conclusion
Automated quantification of MR with 3D-FVCD is feasible and accurate. It is a promising tool for the real-time 3D echocardiographic assessment of patients with MR.
doi:10.4250/jcu.2013.21.2.81
PMCID: PMC3701783  PMID: 23837118
Mitral regurgitation; 3D echocardiography; Quantitative evaluation
15.  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
16.  Comparison of Early Clinical Outcomes Following Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement versus Optimal Medical Therapy in Patients Older than 80 Years with Symptomatic Severe Aortic Stenosis 
Yonsei Medical Journal  2013;54(3):596-602.
Purpose
Transcatheter aortic valve implantation (TAVI) has become an attractive therapeutic strategy for severe aortic stenosis (AS) in elderly patients due to its minimally-invasive nature. Therefore, early results of its clinical outcomes in elderly Korean patients were evaluated.
Materials and Methods
We compared early clinical outcomes of TAVI, surgical aortic valve replacement (SAVR), and optimal medical therapy (OMT) in patients aged ≥80 years with symptomatic severe AS. Treatment groups were allocated as follows: TAVI (n=10), SAVR (n=14), and OMT (n=42).
Results
Baseline clinical characteristics including predicted operative mortality were similar among the three groups. However, patients with New York Heart Association functional class III or IV symptoms and smaller aortic valve area were treated with TAVI or SAVR rather than OMT. In-hospital combined safety endpoints (all-cause mortality, major stroke, peri-procedural myocardial infarction, life-threatening bleeding, major vascular complication, and acute kidney injury) after TAVI or SAVR were significantly lower in the TAVI group than in the SAVR group (10.0% vs. 71.4%, respectively, p=0.005), along with an acceptable rate of symptom improvement and device success. During the follow-up period, the TAVI group showed the lowest rate of 3-month major adverse cardiovascular and cerebrovascular events, a composite of all-cause mortality, myocardial infarction, major stroke, and re-hospitalization (TAVI 0.0% vs. SAVR 50.0% vs. OMT 42.9%, p=0.017).
Conclusion
Treatment with TAVI was associated with lower event rates compared to SAVR or OMT. Therefore, TAVI may be considered as the first therapeutic strategy in selected patients aged ≥80 years with symptomatic severe AS.
doi:10.3349/ymj.2013.54.3.596
PMCID: PMC3635628  PMID: 23549802
Aortic stenosis; transcatheter aortic valve implantation; treatment outcome
18.  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
19.  Ischemia-Reperfusion Injury Leads to Distinct Temporal Cardiac Remodeling in Normal versus Diabetic Mice 
PLoS ONE  2012;7(2):e30450.
Diabetes is associated with higher incidence of myocardial infarction (MI) and increased propensity for subsequent events post-MI. Here we conducted a temporal analysis of the influence of diabetes on cardiac dysfunction and remodeling after ischemia reperfusion (IR) injury in mice. Diabetes was induced using streptozotocin and IR performed by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for up to 42 days. We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV) in both control and diabetic mice. The longitudinal systolic and diastolic strain rate were altered after IR, but there were no significant differences between diabetic mice and controls. However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-(18F)fluoro-D-glucose. Interestingly, after 24 hours reperfusion diabetic mice showed a reduced infarct size and less apoptosis indicated by TUNEL analysis in heart sections. This may be explained by increased levels of autophagy detected in diabetic mice hearts. Similar increases in IR-induced macrophage infiltration detected by CD68 staining indicated no change in inflammation between control and diabetic mice. Over time, control mice subjected to IR developed mild left ventricular dilation whereas diabetic mice exhibited a decrease in both end diastolic left ventricular volume and LVESV with a decreased intraventricular space and thicker left ventricular wall, indicating concentric hypertrophy. This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group. In summary, we demonstrate that diabetes principally influences distinct IR-induced chronic changes in cardiac function and remodeling, while a smaller infarct size and elevated levels of autophagy with similar cardiac function are observed in acute phase.
doi:10.1371/journal.pone.0030450
PMCID: PMC3275560  PMID: 22347376
20.  Early Experience Using a Left Atrial Appendage Occlusion Device in Patients with Atrial Fibrillation 
Yonsei Medical Journal  2011;53(1):83-90.
Purpose
Atrial fibrillation (AF) is one of the major risk factors for ischemic stroke, and 90% of thromboembolisms in these patients arise from the left atrial appendage (LAA). Recently, it has been documented that an LAA occlusion device (OD) is not inferior to warfarin therapy, and that it reduces mortality and risk of stroke in patients with AF.
Materials and Methods
We implanted LAA-ODs in 5 Korean patients (all male, 59.8±7.3 years old) with long-standing persistent AF or permanent AF via a percutaneous trans-septal approach.
Results
1) The major reasons for LAA-OD implantation were high risk of recurrent stroke (80%), labile international neutralizing ratio with hemorrhage (60%), and 3/5 (60%) patients had a past history of failed cardioversion for rhythm control. 2) The mean LA size was 51.3±5.0 mm and LAA size was 25.1×30.1 mm. We implanted the LAA-OD (28.8±3.4 mm device) successfully in all 5 patients with no complications. 3) After eight weeks of anticoagulation, all patients switched from warfarin to anti-platelet agent after confirmation of successful LAA occlusion by trans-esophageal echocardiography.
Conclusion
We report on our early experience with LAA-OD deployment in patients with 1) persistent or permanent AF who cannot tolerate anticoagulation despite significant risk of ischemic stroke, or 2) recurrent stroke in patients who are unable to maintain sinus rhythm.
doi:10.3349/ymj.2012.53.1.83
PMCID: PMC3250321  PMID: 22187236
Atrial fibrillation; left atrial appendage; occlusion device; thromboembolism
21.  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
22.  Constrictive Pericarditis Accompanied by Swine-Origin Influenza A (H1N1) Infection 
Korean Circulation Journal  2010;40(10):539-542.
Swine-origin influenza A (H1N1) is caused by a new strain of the influenza virus. The disease has spread rapidly and was declared a pandemic in April, 2009. So far, however, there is a scarcity of information regarding the complications of swine influenza. A report of the disease in the winter of 2009 in the Southern Hemisphere found that the most common manifestations of influenza A virus infection are upper respiratory tract infection and pneumonia. Although there may be an association between fulminant myocarditis and Swine influenza, cardiovascular complications resulting from swine Influenza A infection are exceedingly rare. We report a case of acute constrictive pericarditis in a healthy subject infected by the swine-origin influenza A (H1N1) virus.
doi:10.4070/kcj.2010.40.10.539
PMCID: PMC2978299  PMID: 21088760
Pericarditis, constrictive; Swine-origin influenza A (H1N1) virus
23.  Targeted Ultrasound Imaging of Apoptosis with Annexin A5 Microbubbles in Acute Doxorubicin-Induced Cardiotoxicity 
Background
The aim of this study was to assess the feasibility of targeted ultrasound imaging on apoptosis with annexin A5 microbubbles (A5MB) in acute doxorubicin-induced cardiotoxicity.
Methods
Avidinated and octafluoropropan-filled phospholipid microbubbles were conjugated with biotinylated annexin A5. To confirm the specific binding of A5MB, flow cytometry was performed with hydrogen peroxide induced apoptosis in rat aorta smooth muscle cells incubated with fluorescein-5-isothiocyanate (FITC) labeled annexin A5 and A5MB. Adult male rats were injected intraperitoneally with 5 mg/kg doxorubicin weekly for 3 weeks (n = 5). Control rats were injected with normal saline (n = 5). At 24 hours after the final treatment, triggering imaging was performed 15 min after an intravenous bolus injection of A5MB for washout of freely circulating microbubbles. After echocardiography, the heart was isolated for histological detection of apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay.
Results
In the in vitro tests, fluorescence intensity was low for healthy cells and high for apoptotic cells when incubated with FITC-labeled annexin A5 and A5MB. Rats treated with doxorubicin showed significant contrast opacification of the myocardium on contrast echocardiography using A5MB. However, no opacification was observed in control rats. Apoptosis was confirmed by TUNEL assay in doxorubicin treated rats.
Conclusion
Acute doxorubicin-induced cardiomyopathy based on early apoptosis can be assessed and imaged with targeted ultrasound imaging using A5MB in rats.
doi:10.4250/jcu.2010.18.3.91
PMCID: PMC2955339  PMID: 20967156
Cardiomyopathy; Apoptosis; Annexin A5; Microbubbles; Echocardiography
24.  Association of Plasma Retinol-Binding Protein 4, Adiponectin, and High Molecular Weight Adiponectin with Insulin Resistance in Non-Diabetic Hypertensive Patients 
Yonsei Medical Journal  2010;51(3):375-384.
Purpose
The aim of this study was to determine whether retinol-binding protein 4 (RBP4), adiponectin and high molecular weight (HMW) adiponectin are associated with insulin resistance (IR) and metabolic parameters in non-diabetic hypertensive patients. Also, we sought to compare the predictive values of these adipocytokines for IR in non-diabetic hypertensive patients.
Materials and Methods
Analyses of RBP4, adiponectin, and HMW adiponectin were performed on 308 non-diabetic hypertensives (148 males, age 58 ± 10 years, 189 non-metabolic syndrome and 119 metabolic syndrome). The homeostasis model assessment (HOMA) index for IR, lipid profiles, and anthropometric measure-ments were assessed.
Results
There was no significant difference in RBP4 levels according to the presence of metabolic syndrome, although adiponectin and HMW adiponectin were significantly lower in metabolic syndrome. Correlation analysis of log RBP4 with IR and metabolic indices revealed that there was no significant correlation of RBP4 with waist circumference (r = 0.056, p = 0.324), HDL cholesterol (r = 0.005, p = 0.934), ApoB/ApoAI ratio (r = 0.066, p = 0.270), and the HOMA index (r = 0.017, p = 0.756). However, adiponectin and HMW adiponectin showed significant correlations with the HOMA index (r = - 0.247, p < 0.001; r = - 0.296, p < 0.001) and metabolic parameters. With IR defined as HOMA index ≥ 2.5, HMW adiponectin did not demonstrate a superior predictive value for IR compared to adiponectin (AUC = 0.680 vs. 0.648, p = 0.083). The predictive value of RBP4 for IR was minimal (AUC = 0.534).
Conclusion
RBP4 was not associated with IR or metabolic indices and the predictive value for IR was minimal in hypertensives. HMW adiponectin didn't have a superior predictive value for IR compared to adiponectin. Therefore, we can suggest that RBP4 and HMW adiponectin don't have more additive information than adiponectin in non-diabetic hypertensives.
doi:10.3349/ymj.2010.51.3.375
PMCID: PMC2852793  PMID: 20376890
Retinol-binding proteins; adiponectin; hypertension; insulin resistance
25.  Increased Inflammation, Reduced Plasma Phospholipid Eicosapentaenoic Acid and Reduced Antioxidant Potential of Treated Hypertensive Patients with Metabolic Syndrome 
Yonsei Medical Journal  2009;50(6):757-763.
Purpose
In the present study, we tested whether the presence of metabolic syndrome (MetS) would worsen the features of inflammation, plasma omega 3 fatty acid levels and antioxidant potential in treated hypertensive patients.
Materials and Methods
Two groups were classified by the components of MetS: a reference group of treated hypertensive subjects: hypertension (HTN) group (n = 39) and with more than two additional MetS components: HTN with Mets group (n = 40). We further compared the parameters between HTN group and HTN with MetS group.
Results
The results showed that age (p < 0.001) and body mass index (BMI) (p < 0.001) were significantly different between HTN group and HTN with MetS group. Age- and BMI-adjusted total radical trapping antioxidant potential (TRAP) (p < 0.01) was significantly lower, whereas age- and BMI-adjusted CD (p < 0.05) and interleukin (IL) 6 (p < 0.05) were significantly higher in HTN with MetS group than in HTN group. Moreover, HTN with MetS group had significantly lower levels of age- and BMI-adjusted plasma phospholipid eicosapentaenoic acid (EPA) than HTN group (p < 0.05). On the other hand, the levels of age- and BMI-adjusted intracellular cell adhesion molecule-1 (ICAM-1), adiponectin and high molecular weight (HMW)-adiponectin were not significantly different between the groups.
Conclusion
In conclusion, our results showed increased inflammatory marker, reduced antioxidant potential and EPA levels in treated hypertensive patients in the presence of MetS, suggesting the importance of changes of therapeutic lifestyle to modify the features of MetS.
doi:10.3349/ymj.2009.50.6.757
PMCID: PMC2796400  PMID: 20046414
Metabolic syndrome X; hypertension; oxidative stress; eicosapentaenoic acid; antioxidants; cytokines

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