Endothelial dysfunction in subfertile women with polycystic ovary syndrome.

RESEARCH QUESTION: Is there an association between post-occlusive reactive hyperaemia (PORH) and ovarian stimulation in women with normoandrogenaemic polycystic ovary syndrome (PCOS)? DESIGN: Women eligible for IVF at an academic fertility centre were invited to join this prospective study. Microvascular endothelial function was measured as PORH by laser Doppler flowmetry (LDF) before and after ovarian stimulation. Metabolic characteristics, hormone profiles and biochemical markers were analysed. RESULTS: Thirty-four normoandrogenaemic women with PCOS and 36 normoandrogenaemic women without PCOS were included. The PCOS group displayed higher C-reactive protein levels and insulin resistance (P = 0.048 and P = 0.025, respectively). No significant difference was found in microcirculatory function between the groups at baseline. After ovarian stimulation, PORH was enhanced in the control group (slope 7.1 ± 3.3 versus 9.7 ± 4.5; P = 0.007; peak flow 30.7 ± 16.3 versus 43.5 ± 17.3, P = 0.008; however, the PCOS group experienced a blunting response to supraphysiological hormone status (slope 8.2 ± 5.1 versus 7.2 ± 4.3, P = 0.212; peak flow, 38.8 ± 19.4 versus 37.0 ± 21.8, P = 0.895). CONCLUSIONS: Impaired microcirculatory function could be found using a non-invasive LDF technique in normoandrogenaemic women with PCOS undergoing IVF, indicating early changes in vascular endothelial dysfunction. Future observational studies should clarify whether PORH measurement might help predict IVF prognosis or obstetric complications.

Resuscitation outcomes of a wireless ECG telemonitoring system for cardiovascular ward patients experiencing in-hospital cardiac arrest.

BACKGROUND/PURPOSE: In-hospital cardiac arrest is a serious issue for hospitalized patients. The documented initial rhythm and detected medical events have been reported to influence the survival of cardiopulmonary resuscitation. This study aimed to identify the effect of continuous real-time electrocardiogram (ECG) monitoring on the prognosis of resuscitated patients in a general cardiac ward. METHODS: We conducted this retrospective study using medical records of hospitalized patients in a cardiovascular ward who experienced an in-hospital cardiac arrest and received cardiopulmonary resuscitation from February 2015 to December 2018. The patients who were considered to be at high risk of cardiac events such as ventricular arrhythmia would receive continuous ECG monitoring. A wireless ECG telemonitoring system was introduced to replace traditional bedside ECG monitors. The outcome measures were the initial success of resuscitation, 24-h survival after resuscitation, and survival to discharge. RESULTS: We enrolled 115 patients with a cardiac arrest during hospitalization, of whom 73 (63%) patients received wireless ECG telemonitoring. Patients receiving continuous ECG monitoring were associated with higher opportunities of initial success of resuscitation and 24-h survival after resuscitation (67.1% vs. 40.5%, p = 0.005; and 49.3% vs. 26.2%, p = 0.015, respectively) when comparing to the non-monitoring group; but no significant difference in survival to discharge (21.9% vs. 16.7%, p = 0.498) was observed. With adjustment of the covariates, the monitoring group was associated with a higher likelihood to reach the initial success of resuscitation (odds ratios [ORs], 3.21; 95% confidence interval [CI], 1.03-9.98). However, the effect of monitoring on 24-h survival and survival to discharge was close to null after adjusting for covariates. CONCLUSION: A wireless ECG telemonitoring system were beneficial to the initial success of resuscitation for patients at high risk of cardiovascular events suffering an in-hospital cardiac arrest; but had less impact on 24-h survival and survival to discharge.

Mid-term survival of patients with chronic kidney disease after extracorporeal membrane oxygenation.

OBJECTIVES: Chronic kidney disease (CKD) impairs the elimination of fluids, electrolytes and metabolic wastes, which can affect the outcomes of extracorporeal membrane oxygenation (ECMO) treatment. This study aimed to elucidate the impact of CKD on in-hospital mortality and mid-term survival of adult patients who received ECMO treatment. METHODS: Patients who received first-time ECMO treatment between 1 January 2003 and 31 December 2013 were included. Those with CKD were identified and matched to patients without CKD using a 1:2 ratio and were followed for 3 years. The study outcomes included in-hospital outcomes and the 3-year mortality rate. A subgroup analysis was conducted by comparing the dialytic patients with the non-dialytic CKD patients. RESULTS: The study comprised 1008 CKD patients and 2016 non-CKD patients after propensity score matching. The CKD patients had higher in-hospital mortality rates [69.5% vs 62.2%; adjusted odds ratio 1.41; 95% confidence interval (CI) 1.15-1.72] than the non-CKD patients. The 3-year mortality rate was 80.4% in the CKD group and 68% in the non-CKD group (adjusted hazard ratio 1.17; 95% CI 1.06-1.28). The subgroup analysis showed that the 3-year mortality rates were 84.5% and 78.4% in the dialytic and non-dialytic patients, respectively. No difference in the 3-year mortality rate was noted between the 2 CKD subgroups (P = 0.111). CONCLUSIONS: CKD was associated with increased risks of in-hospital and mid-term mortalities in patients who received ECMO treatment. Furthermore, no difference in survival was observed between the patients with end-stage renal disease and non-dialytic CKD patients.

Late migration of a Sideris septal occluder device for closure of atrial septal defect into the left atrium with mitral valve obstruction.

The transcatheter closure of atrial septal defects provides an alternative to surgery, and various devices, such as the Sideris buttoned device, have been prescribed. Late complications have been rare and have not yet been reported within 2 years of implantation. This report presents a case of delayed migration of a Sideris buttoned device occurring 6 years after successful implantation. In conclusion, this report provides a reminder of the need for careful long-term follow-up of patients receiving transcatheter closure of atrial septal defects, particularly in cases involving the implantation of early-generated devices.

Four and half lim protein 2 (FHL2) stimulates osteoblast differentiation.

UNLABELLED: FHL2, a molecule that interacts with many integrins and transcription factors, was found to play an important role in osteoblast differentiation. Overexpression of FHL2 increases the accumulation of osteoblast differentiation markers and matrix mineralization, whereas FHL2 deficiency results in inhibition of osteoblast differentiation and decreased bone formation. INTRODUCTION: Integrin-matrix interaction plays a critical role in osteoblast function. It has been shown that the cytoplasmic domains of integrin beta subunits mediate signal transduction induced by integrin-matrix interaction. We reasoned that the identification of proteins interacting with beta-cytoplasmic tails followed by analysis of the function of these proteins would enhance our understanding on integrin signaling and the roles of these proteins in osteoblast activities. MATERIALS AND METHODS: Yeast two hybrid assay was used to identify proteins interacting with the cytoplasmic domain of integrin beta5 subunit. The association of these proteins with integrin alphavbeta5 was confirmed by confocal analysis and co-immunoprecipitation. A stable MC3T3-E1 cells line overexpressing Four and Half Lim Protein 2 (FHL2) and mouse osteoblasts deficient in FHL2 were used to study the roles of FHL2 in osteoblast differentiation and bone formation. Matrix protein expression was determined by mRNA analysis and Western blotting. Matrix mineralization was detected by Alizarin red staining. Alkaline phosphatase activity was also measured. muCT was used to determine bone histomorphometry. RESULTS AND CONCLUSIONS: FHL2 and actin-binding proteins, palladin and filamin A, were identified as proteins interacting with beta5 cytoplasmic domain. FHL2 co-localized with alphavbeta5 at the focal adhesion sites in association with palladin and filamin A. FHL2 was also present in nuclei. Osteoblasts overexpressing FHL2 exhibited increased adhesion to and migration on matrix proteins. Conversely, FHL2 stimulation of CREB activity was dependent on integrin function because it was inhibited by Gly-Arg-Gly-Asp-Ser (GRGDS) peptide. The expression of osteoblast differentiation markers and Msx2 was upregulated, and bone matrix mineralization was increased in FHL2 overexpressing cells. In contrast, FHL2-deficient bone marrow cells and osteoblasts displayed decreased osteoblast colony formation and differentiation, respectively, compared with wildtype cells. Moreover, FHL2-deficient female mice exhibited greater bone loss than the wildtype littermates after ovariectomy. Thus, FHL2 plays an important role in osteoblast differentiation and bone formation.

Predictors of stable outcome in treating chronic heart failure patients with carvedilol.

Carverdilol has a variable outcome in treating patients with chronic heart failure. This prospective single-center study evaluated the predictors of clinical variables in determining favorable outcomes in treating chronic heart failure patients with carvedilol. The relation between clinical variables and maintenance doses of carvedilol was also determined. Seventy chronic heart failure patients (mean age, 62.2 years, 50 males and 20 females) with a left ventricular ejection fraction < 35% and functional class II-III were enrolled in the study. The patients were clinically followed-up for at least 24 months. Patients were considered to have a favorable outcome if they had no decreases in functional class or quality-of-life score, an increase in left ventricular ejection fraction>5%, were not admitted to hospital due to worsening heart failure, and free of cardiac mortality. Patients with favorable outcomes had a younger age (P = 0.021), higher baseline systolic blood pressure (P = 0.080), better baseline functional class (P = 0.001), and a higher tolerated dose of carvedilol (P = 0.026) than those in the unfavorable group. In this primarily Chinese cohort of chronic heart failure patients, those with favorable outcomes were likely to be young, have a high baseline systolic blood pressure, and good baseline functional class.

Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart.

Hearts of mice lacking Isl1, a LIM homeodomain transcription factor, are completely missing the outflow tract, right ventricle, and much of the atria. isl1 expression and lineage tracing of isl1-expressing progenitors demonstrate that Isl1 is a marker for a distinct population of undifferentiated cardiac progenitors that give rise to the cardiac segments missing in isl1 mutants. Isl1 function is required for these progenitors to contribute to the heart. In isl1 mutants, isl1-expressing progenitors are progressively reduced in number, and FGF and BMP growth factors are downregulated. Our studies define two sets of cardiogenic precursors, one of which expresses and requires Isl1 and the other of which does not. Our results have implications for the development of specific cardiac lineages, left-right asymmetry, cardiac evolution, and isolation of cardiac progenitor cells.

Embryonic atrial function is essential for mouse embryogenesis, cardiac morphogenesis and angiogenesis.

The requirement for atrial function in developing heart is unknown. To address this question, we have generated mice deficient in atrial myosin light chain 2 (MLC2a), a major structural component of the atrial myofibrillar apparatus. Inactivation of the Mlc2a gene resulted in severely diminished atrial contraction and consequent embryonic lethality at ED10.5-11.5, demonstrating that atrial function is essential for embryogenesis. Our data also address two longstanding questions in cardiovascular development: the connection between function and form during cardiac morphogenesis, and the requirement for cardiac function during vascular development. Diminished atrial function in MLC2a-null embryos resulted in a number of consistent secondary abnormalities in both cardiac morphogenesis and angiogenesis. Our results unequivocally demonstrate that normal cardiac function is directly linked to normal morphogenic development of heart and vasculature. These data have important implications for the etiology of congenital heart disease.

Feasibility of simplifying balloon mitral valvuloplasty by obviating left-sided cardiac catheterization using on-line guidance with transesophageal echocardiography.

STUDY OBJECTIVES: The purpose of this study was to evaluate the feasibility of simplifying balloon mitral valvuloplasty through the obviation of left-sided cardiac catheterization using on-line guidance with transesophageal echocardiography in patients with mitral stenosis. SETTING: A tertiary care medical center DESIGN: Patients who were eligible for balloon mitral valvuloplasty were enrolled into the study if they had no evidence of ischemic heart disease. Sixty-six patients (50 women and 16 men) met the criteria. Balloon mitral valvuloplasty was performed through right-sided cardiac catheterization using adjunctive on-line guidance with transesophageal echocardiography. Left-sided catheterization was obviated. MEASUREMENT AND RESULTS: Balloon mitral valvuloplasty was smoothly performed in all patients. Successful dilatation (postprocedural mitral orifice area, > 1.5 cm(2); or increment in mitral orifice area, >or= 50%) was achieved in 50 patients (75.8%). The mean (+/- SD) mitral orifice area increased from 1.08 +/- 0.23 cm(2) to 1.68 +/- 0.39 cm(2) (p = 0.0000). There were no in-hospital deaths, no patients with cardiac tamponade, or complications necessitating an emergency cardiac operation. The mean fluoroscopy time was 7.6 +/- 3.9 min, and the total procedure time was 50.2 +/- 15.0 min. CONCLUSION: It is feasible and safe to simplify balloon mitral valvuloplasty by obviating left-sided cardiac catheterization in selected patients with mitral stenosis using adjunctive on-line guidance with transesophageal echocardiography.

Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice.

Caveolins are important components of caveolae, which have been implicated in vesicular trafficking and signal transduction. To investigate the in vivo significance of Caveolins in mammals, we generated mice deficient in the caveolin-1 (cav-1) gene and have shown that, in the absence of Cav-1, no caveolae structures were observed in several nonmuscle cell types. Although cav-1(-/-) mice are viable, histological examination and echocardiography identified a spectrum of characteristics of dilated cardiomyopathy in the left ventricular chamber of the cav-1-deficient hearts, including an enlarged ventricular chamber diameter, thin posterior wall, and decreased contractility. These animals also have marked right ventricular hypertrophy, suggesting a chronic increase in pulmonary artery pressure. Direct measurement of pulmonary artery pressure and histological analysis revealed that the cav-1(-/-) mice exhibit pulmonary hypertension, which may contribute to the right ventricle hypertrophy. In addition, the loss of Cav-1 leads to a dramatic increase in systemic NO levels. Our studies provided in vivo evidence that cav-1 is essential for the control of systemic NO levels and normal cardiopulmonary function.

Intra-atrial thrombolytic therapy for dissolution of chronic left atrial thrombi in patients undergoing balloon mitral commissurotomy.

The purpose of this study was to evaluate the solubility of left atrial thrombi to thrombolytics after failure of long-term anticoagulant therapy in patient with mitral stenosis. One hundred and eighty-one consecutive patients with mitral valve area < or = 1.5 cm(2) and without severe mitral regurgitation were screened with echocardiography; 30 were found to have left atrial thrombi. Follow-up echocardiography performed 7.4 +/- 5.6 months after warfarin therapy revealed that 8/30 of patients had complete dissolution and 3/30 had partial dissolution of the thrombi. Thirteen patients with residual isolated appendageal thrombi underwent balloon mitral commissurotomy and were randomized into four groups at the end of balloon mitral commissurotomy: group A, receiving intra-atrial infusion of heparin and tissue plasminogen activator (t-PA; n = 4); group B, heparin and streptokinase (n = 3); group C, heparin (n = 3); and group D, acting as control (n = 3). It was found that only two patients in the t-PA group had their thrombi either completely or partially dissolved within 48 hr. Thus, this study suggests that t-PA may have the potential of dissolving chronic left atrial thrombi.

Percutaneous transseptal mitral valvuloplasty in the presence of undegenerated septum primum.

A 37-year-old woman had progressive shortness of breath and mitral stenosis was diagnosed. Despite the unusual finding of undegenerated septum primum on echocardiography and angiography, percutaneous transseptal mitral commissurotomy was successfully performed in this patient with rheumatic mitral stenosis under the guidance of online transesophageal echocardiography.