Alcohol Septal Ablation for Hypertrophic Cardiomyopathy Guided by Intracoronary Myocardial Contrast Echocardiography to Reduce Myocardial Damage.

Septal reduction therapy (SRT) is indicated for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). SRT includes surgical myectomy and alcohol septal ablation (ASA). The outcome between SRTs are similar except complete atrioventricular (AV) block. Intracoronary myocardial contrast echocardiography is used to minimize myocardial damage by ASA. We report a case of 40-year-old male who was diagnosed of HOCM with progressed symptoms under optimal medication. Echocardiography revealed peak velocity cross left ventricular outflow tract (LVOT) 5.3 m/s, systolic anterior motion (SAM) of mitral valve with eccentric mitral regurgitation (MR) and interventricular septal thickness 16 mm. Alcohol (99.5%) 1.5 mL was injected into the first small branch of the first septal artery, under precise localization by intracoronary myocardial contrast echocardiography. The pressure gradient of apex-LVOT-aorta reduced from 90 to 20 mmHg after ASA. No AV block was noted after the procedure and echocardiography revealed improved peak velocity cross LVOT and interventricular septal thickness. No more SAM or eccentric MR was observed. Previous studies recommended ASA reserved for patients with higher surgical risk and severe comorbidities. However, a recent study showed that young adults had better long-term survival and only one-half pacemaker implantation rate than older group following ASA. Under the guidance of intracoronary myocardial contrast, target vessel could be precisely localized to small branch from a septal artery to decrease myocardial damage. Therefore, ASA may be considered as the first-line SRT for symptomatic HOCM due to minimal invasiveness and effective outcome.

Promotion of the Differentiation of Dental Pulp Stem Cells into Oligodendrocytes by Knockdown of Heat Shock Protein 27.

Stem cell-based therapy has been evaluated in many different clinical trials for various diseases. This capability was applied in various neurodegenerative diseases, such as multiple sclerosis, which is characterized by demyelination, axonal injury, and neuronal loss. Dental pulp stem cells (DPSCs) are mesenchymal stem cells from the oral cavity that have been studied with potential application for the regeneration of different tissues. Heat shock protein 27 (HSP27) regulates neurogenesis in the process of neural differentiation of placenta multipotent stem cells. Here, we hypothesize that HSP27 expression is also critical for the neural differentiation of DPSCs. An evaluation of the possible role of HSP27 in the differentiation of DPSCs was performed using gene knockdown and neural immunofluorescent staining. We found that HSP27 played a role in the differentiation of DPSCs and that knockdown of HSP27 in DPSCs rendered cells to oligodendrocyte progenitors; i.e., small hairpin specific for HSP27 DPSCs exhibited NG2-positive immunoreactivity and gave rise to oligodendrocytes or type-2 astrocytes. This neural differentiation of DPSCs may have clinical significance in the treatment of patients with neurodegenerative diseases. In conclusion, our data provide an example of the oligodendrocyte differentiation of a DPSC model, which may be applied in human regenerative medicine.

The correlation between three-dimensional vena contracta area and aortic regurgitation index in patients with aortic regurgitation.

OBJECTIVES: The aims of this study are to explore the correlation between the three-dimensional vena contracta (3D VC) area and the aortic regurgitation (AR) index and to determine AR severity using the 3D VC area. BACKGROUND: The geometry of regurgitant jets is complex in patients with AR. The 3D VC area can be easily cropped using any plane and we can obtain the complex geometry of the VC area. METHODS: Full-volume three-dimensional (3D) color flow datasets were generated using the trans-thoracic parasternal approach. The AR jet could be well visualized and analyzed in three orthogonal planes using dedicated software. RESULTS: We consecutively analyzed 77 AR patients with comprehensive 2D and 3D echocardiographic data. The 3D VC area increased proportionately with increasing AR severity using the AR index method (F = 86.1, P < 0.001) and correlated well with effective regurgitant orifice (P < 0.001). The cutoff value of the VC area was < 30 mm(2) (sensitivity = 90% and specificity = 88%) for predicting mild AR and > 50 mm(2) (sensitivity = 92% and specificity = 87%) for predicting severe AR. CONCLUSION: 3D color flow VC area measurement provides a simple and accurate method for assessing the severity of AR.

Expression of Nik-related kinase in smooth muscle cells attenuates vascular inflammation and intimal hyperplasia.

Inflammation of the vascular microenvironment modulates distinct types of vascular cells, and plays important roles in promoting atherosclerosis, stenosis/restenosis, and vascular-related diseases. Nik-related kinase (Nrk), a member of the Ste20-type kinase family, has been reported to be selectively expressed in embryonic skeletal muscle. However, whether Nrk is expressed in adult vascular smooth muscle, and if it influences intimal hyperplasia is unclear. Here, we found that Nrk is abundantly expressed in cultured vascular smooth muscle cells (VSMC) and mouse arterial intima. Treatment of mouse VSMCs with lipopolysaccharide (LPS) or platelet-derived growth factor significantly reduced Nrk expression. In addition, expression of Nrk was significantly reduced in regions of neointimal formation caused by guide-wire carotid artery injuries in mice, as well as in human atherosclerotic tissues, when compared to normal vessels. We identified that expression of matrix metalloproteinases (MMP3, MMP8 and MMP12) and inflammatory cytokines/chemokines (CCL6, CCL8, CCL11, CXCL1, CXCL3, CXCL5 and CXCL9) are synergistically induced by Nrk siRNA in LPS-treated mouse VSMCs. Moreover, we found that resveratrol significantly impaired LPS- and Nrk siRNA-induced expression of MMP3, CCL8, CCL11, CXCL3 and CXCL5. These results suggested that Nrk may play important roles in regulating pathological progression of atherosclerosis or neointimal- hyperplasia-related vascular diseases.

Is guidewire exchange a better approach for subclavian vein re-catheterization for chronic hemodialysis patients?

BACKGROUND: The objectives of this study were to compare outcomes and survival rates of subclavian vein re-catheterization through guide wire exchange (GWE) or de novo insertion (DN). MATERIALS AND METHODS: The study was conducted in a retrospective manner. Medical records of 36 patients who received percutaneous subclavian vein re-catheterization for hemodialysis in our institution during the period from April 1, 2001 to September 30, 2004 were reviewed. All patients had at least 2 catheter insertions records in our institute. Incidences of adverse events (infection, thrombosis) were compared between GWE and DN groups using x2 test. Predictors for adverse event occurrences were analyzed using logistic regression models. Cox proportional hazard model was used to investigate the predictors for adverse event-free catheter days. Kaplan-Meire survival curves were computed and compared using log rank test. RESULTS: Information were generated from 98 catheters (41 from DN, 57 from GWE groups). The average catheter usage was 2.8+/-0.9 devices per patient and the mean catheter-indwelling-day was 125.4+/-129.5 days in this cohort. We found GWE group had significantly lower thrombosis rate (49.1% vs. 85.4% for DN group, P<0.000) in general. Surgical approach was a significant risk factors for catheter thrombosis (GWE vs. DN, odds ratio=0.261, P=0.05). The actuarial survival rates for GWE were > or =30 days, 85.4%; > or =60 days, 75.5%; > or =90 days, 64.5%; > or =180 days, 44.3%. The actuarial survival rates for DN were > or =30 days, 70.7%; > or =60 days, 58.5%; > or =90 days, 34.2%; > or =180 days, 18.4%. GWE group catheters had significantly higher catheter survival rates (P=0.0009). Mahukar catheter (hazard ratio 0.514, P=0.03), non-shock (hazard ratio 3.358, P=0.04), and older age (hazard ratio 0.958, P=0.026) were predictors of adverse event-free remaining catheter days. CONCLUSION: We suggest that GWE might be a favorable option over DN insertion when revised subclavian vein catheterization is inevitable. GWE can be performed repeatedly without compromising catheter outcomes.

Gastric Anatomic Type Is Associated with Obesity and Gender.

OBJECTIVE: To enhance our understanding of the associations among gastric anatomy, obesity, and gender. METHODS: 777 randomly selected participants received health checkups, including a series of radiographs of the upper gastrointestinal tract (UGI); the findings were linked with each corresponding subject's gender and BMI. We measured the length, angle, and different portions of the stomach with the subjects in the standing position using radiographs to classify all individuals into anatomic types 1 through 6 based on gastric morphology. The gastric morphology was identified based on the initial UGI examination: 166 follow-up UGI radiographs at 12 ± 1.5 months to evaluate whether the stability of gastric anatomy persisted over time. RESULTS: There was a significant difference in anatomic types between females and males (p < 0.001). The proportions of men with certain types (e.g., barium initially pools in a retroflexed fundus) were significantly higher than those of women; these participants were more likely to be overweight/obese (p < 0.001) compared with participants with other anatomic types. Additionally, the proportion of women with gastroptosis was significantly higher than that of men; participants with this type were less likely to be overweight/obese (p < 0.001). CONCLUSION: Gastric anatomic types were associated with obesity and gender.

Value of parasternal long-axis vena contracta width for predicting severity of aortic regurgitation in left ventricular systolic dysfunction.

Correlations derived for the relations between parasternal long-axis vena contracta width and effective regurgitant orifice area, regurgitant volume, and regurgitant fraction were highly significant. A vena contracta width of <3.0 or >5.0 mm provided excellent specificity for nonsevere and severe aortic regurgitation, respectively.

Plasma B-type natriuretic peptide in predicting outcomes of elective coronary artery bypass surgery.

The risks of surgery and its clinical outcome are of great importance for both patients and physicians when choosing coronary artery bypass (CABG) surgery for coronary artery disease. The purpose of the current study was to clarify the relationship between serum B-type natriuretic peptide (BNP) and patient clinical outcome. Seventy-six eligible patients who underwent CABG were enrolled into the prospective study. Venous blood samples were drawn for serum BNP and N-terminal (NT)-proBNP levels measurement on preoperative Day 1, postoperative Day 1, and postoperative Day 7. Clinical end points were: (1) intensive care unit (ICU) stay longer than 4 days postoperatively and/or hospital stay longer than 13 days postoperatively; (2) major complications and poor outcomes. Patients who had prolonged ICU stay and hospitalization had significantly higher postoperative Day 1 BNP and postoperative Day 1 NT-proBNP level (p = 0.02 and 0.005, respectively). Age was significantly older in patients with prolonged ICU stay and hospitalization than those without prolonged ICU stay and hospitalization (p = 0.03). Serum creatinine level was also significantly increased in patients with prolonged ICU stay and hospitalization (p = 0.009). However, age was the only remaining factor that correlated with prolonged ICU stay and hospitalization in the multivariate logistic regression model. These results suggest that research using BNP and NT-proBNP for predicting ICU stay and hospitalization in patients who have undergone CABG must adjust risk factors to present a more appropriate estimation of its clinical outcome.

Carotid intima-media thickness and plaque occurrence in predicting stable angiographic coronary artery disease.

BACKGROUND: Carotid intima-media thickness (CIMT) and plaque formation have been used as surrogate end-points for evaluating the regression and/or progression of atherosclerotic cardiovascular disease, but their predictive value for stable coronary artery disease (CAD) is inconclusive. METHODS: Carotid ultrasonography was performed in patients who underwent noninvasive multislice computed tomography (MSCT) angiography for CAD suspected, due to chest pain. CIMT and plaque formation on the left and right common carotid arteries (CCAs), carotid bulb (CB), and proximal internal carotid arteries (ICAs) were evaluated, and the relationship between angiographic CAD, CIMT, and plaque formation was determined. RESULTS: 120 patients (95 male; 25 female), with a mean age ± standard deviation of 61 ± 11 years (range: 35-89 years) were recruited. Because age had a significant impact on CAD (r = 0.191; P = 0.036), CCA plaques (r = 0.368; P = 0.001), ICA plaques (r = 0.334; P = 0.004), and mean CIMT (r = 0.436; P = 0.001), patients were divided into two groups aged <60 years and ≥60 years. In the <60 years group, CIMT-CB was significantly higher in patients with CAD (P = 0.041), while in the ≥60 years group, mean CIMT, CIMT-CCA, and CIMT-CB were significantly higher in patients with CAD (P < 0.05, for each). In both groups, the occurrence of carotid plaques was significantly higher in patients with CAD than in those without CAD (P < 0.007, for each). After controlling for other risk factors, carotid plaques were an independent predictor of CAD in both groups (P < 0.05, for each), while CIMT-CB could independently predict CAD only in patients ≥60 years old (P = 0.031). CONCLUSION: Our findings suggest that carotid plaques are a strong predictor of stable CAD. However, CIMT-CB could predict stable CAD only in patients over 60 years of age.

YC-1, a potent antithrombotic agent, induces lipolysis through the PKA pathway in rat visceral fat cells.

This study investigated the effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), a soluble guanylyl cyclase (sGC) activator and potential antithrombotic agent, on lipolysis in isolated visceral fat cells of the rat. Visceral fat cells were isolated from epididymal fat pads of rats and treated with YC-1 at different doses and times. Glycerol release, and intracellular cAMP and cGMP levels were analyzed by specific kits. Moreover, several inhibitors or drugs were used to examine the signal transduction pathways of YC-1-induced lipolysis in adipocytes. Herein we report that YC-1 stimulated glycerol release in dose- and time-dependent manners. Intracellular cAMP and cGMP levels of adipocytes both increased in time-dependent manners, but elevation of the cGMP level was faster and higher than that of the cAMP level after YC-1 treatment. An sGC inhibitor (ODQ) inhibited YC-1-induced glycerol release, indicating the involvement of sGC in YC-1-induced lipolysis. Administration of insulin, an activator of type-3B phosphodiesterase (PDE-3B), attenuated YC-1-induced lipolysis, indicating that elevation of the cAMP level is an important step in the lipolytic effect of YC-1. In addition, YC-1-induced lipolysis was inhibited by a protein kinase A (PKA) inhibitor (KT5720) but not by a PKG inhibitor (KT5823), indicating that YC-1-induced lipolysis occurs through a PKA-dependent pathway. A Western blot analysis showed that extracellular signal-regulated kinase was not phosphorylated by YC-1 treatment. In conclusion, our results suggest that YC-1 might stimulate lipolysis via activation of sGC/cGMP and then activation of the cAMP/PKA signaling cascade in isolated rat visceral adipocytes.

Prediction of severity of isolated aortic regurgitation by echocardiography: an aortic regurgitation index study.

BACKGROUND: No single precise qualitative method is recommended for evaluating the severity of aortic regurgitation (AR). Quantitative methods for AR assessment are, typically, cumbersome and time-consuming. The purpose of this study was to develop a more comprehensive method for predicting the severity of AR. METHODS: In all, 79 patients with normal left ventricular systolic function and at least mild AR were included in this prospective study. The standard references for evaluating AR severity were quantitative methods. The AR index consisted of 5 echocardiographic parameters: jet width ratio, vena contracta width, pressure half-time, jet density, and diastolic flow reversal in the descending aorta. Each parameter was scored on a 3-point scale from 1 to 3. The AR index was calculated as the sum of each score divided by the number of parameters. Thus, an increasing AR index score from 1 to 3 was indicative of increasing regurgitation. RESULT: The study demonstrated that the numeric value of AR index increased proportionately to the quantitative grading of AR severity, and proved to be an accurate predictor for AR severity. A 1.8 threshold for the AR index offered a high level of sensitivity and negative predictive value for severe AR. The possibility of missing severe AR was low with AR index less than 1.8. A 2.6 threshold for the AR index provided high specificity and positive predictive value for severe AR. The possibility of diagnosing severe AR was extremely high with AR index of 2.6 or more. CONCLUSION: AR index provided a more comprehensive method for predicting the degree of AR severity in this study. We suggest that the AR index should be considered for any evaluation of the severity of AR.