Development of a Hospital Outcome Measure Intended for Use With Electronic Health Records: 30-Day Risk-standardized Mortality After Acute Myocardial Infarction.

Background: Electronic health records (EHRs) offer the opportunity to transform quality improvement by using clinical data for comparing hospital performance without the burden of chart abstraction. However, current performance measures using EHRs are lacking.

Methods: With support from the Centers for Medicare & Medicaid Services (CMS), we developed an outcome measure of hospital risk-standardized 30-day mortality rates for patients with acute myocardial infarction for use with EHR data.

Intravenous fluids in acute decompensated heart failure.

Objectives: This study sought to determine the use of intravenous fluids in the early care of patients with acute decompensated heart failure (HF) who are treated with loop diuretics.

Background: Intravenous fluids are routinely provided to many hospitalized patients.

Methods: We conducted a retrospective cohort study of patients admitted with HF to 346 hospitals from 2009 to 2010.

Development and use of an administrative claims measure for profiling hospital-wide performance on 30-day unplanned readmission.

Background: Existing publicly reported readmission measures are condition-specific, representing less than 20% of adult hospitalizations. An all-condition measure may better measure quality and promote innovation.

Objective: To develop an all-condition, hospital-wide readmission measure.

Patterns of change in nesiritide use in patients with heart failure: how hospitals react to new information.

Objectives: This study sought to determine hospital patterns of change in use of nesiritide over a 6-year period after publications of safety concerns in 2005 and to identify hospital characteristics associated with these patterns.

Background: The changing nature of medical evidence often requires a change in practice. Nesiritide was commercialized in 2001 for early relief of dyspnea in patients with decompensated heart failure.

Hospital variation in intravenous inotrope use for patients hospitalized with heart failure: insights from Get With The Guidelines.

Background: Prior claims analyses suggest that the use of intravenous inotropic therapy for patients hospitalized with heart failure varies substantially by hospital. Whether differences in the clinical characteristics of the patients explain observed differences in the use of inotropic therapy is not known.

Methods And Results: We sought to characterize institutional variation in inotrope use among patients hospitalized with heart failure before and after accounting for clinical factors of patients.

Spending more, doing more, or both? An alternative method for quantifying utilization during hospitalizations.

Background: Because relative value unit (RVU)-based costs vary across hospitals, it is difficult to use them to compare hospital utilization.

Objective: To compare estimates of hospital utilization using RVU-based costs and standardized costs.

Design: Retrospective cohort.

Measuring cardiac waste: the premier cardiac waste measures.

The authors developed 8 measures of waste associated with cardiac procedures to assist hospitals in comparing their performance with peer facilities. Measure selection was based on review of the research literature, clinical guidelines, and consultation with key stakeholders. Development and validation used the data from 261 hospitals in a split-sample design.

Hospital patterns of use of positive inotropic agents in patients with heart failure.

Objectives: This study sought to determine hospital variation in the use of positive inotropic agents in patients with heart failure.

Background: Clinical guidelines recommend targeted use of positive inotropic agents in highly selected patients, but data are limited and the recommendations are not specific.

Methods: We analyzed data from 376 hospitals including 189,948 hospitalizations for heart failure from 2009 through 2010.

Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells.

Mammalian target of rapamycin (mTOR) activity is regulated by assembly of two functionally distinct complexes, mTORC1 and mTORC2. In syndecan-4 (S4) null endothelial cells, mTORC2 activity is reduced, resulting in decreased Akt activation, while mTORC1 activity is increased. Levels of rictor, mLST8, and mSin-1 are unchanged in total cell lysates but decreased in the rafts of S4(-/-) endothelial cells, as is the level of PKCalpha.

Stem cell therapies in cardiovascular disease A "realistic" appraisal.

The possibility of reconstituting the damaged heart has introduced a new paradigm in cardiovascular biology and created the potential for a new therapeutic approach in the cardiovascular field, where there is a compelling need for innovative treatments. While the results of animal and early clinical studies are encouraging, the more direct use of cell-based therapies in patients is still long-reached. Gaps in our basic understanding of mechanisms, lack of important randomized, double blind, and controlled clinical trials, as well as technology development for cell production are among challenges to be overcome before full translation of cell based therapies in clinical arena.

PKCalpha activates eNOS and increases arterial blood flow in vivo.

Endothelial nitric oxide synthase (eNOS) plays an important role in control of vascular tone and angiogenesis among other functions. Its regulation is complex and has not been fully established. Several studies have emphasized the importance of phosphorylation in the regulation of eNOS activity.

Regulation of protein kinase B/Akt activity and Ser473 phosphorylation by protein kinase Calpha in endothelial cells.

Protein kinase Balpha (PKBalpha/Akt-1) is a key mediator of multiple signaling pathways involved in angiogenesis, cell proliferation and apoptosis among others. The unphosphorylated form of Akt-1 is virtually inactive and its full activation requires two phosphatidylinositol-3,4,5-triphosphate-dependent phosphorylation events, Thr308 by 3-phosphoinositide-dependent kinase-1 (PDK1) and Ser473 by an undefined kinase that has been termed PDK2. Recent studies have suggested that the Ser473 kinase is a plasma membrane raft-associated kinase.

Syndecan-4 modulates basic fibroblast growth factor 2 signaling in vivo.

Syndecan-4 is one of the principal heparan sulfate-carrying proteins on the cell surface. Unlike other members of syndecan family, syndecan-4 mediates phosphatidylinositol 4,5-bisphosphate 2 (PIP(2))-dependent PKC-alpha activation, and overexpression of syndecan-4 in vitro results in enhanced FGF2 signaling. The present study was designed to test the functional effect of increased syndecan-4 expression in endothelial cells in transgenic mice.

Modulation of microvascular signaling by heparan sulfate matrix: studies in syndecan-4 transgenic mice.

The onset of tissue ischemia is associated with significant changes in the expression of heparan sulfate- (HS) carrying core proteins that, in turn, lead to alterations in composition of the extracellular HS matrix. Since HS can bind numerous growth factors and cytokines, such changes in the HS matrix content can have profound effects on the ability of these factors to interact with their target cells. To investigate the role of increased HS matrix content on microvascular function, we used alpha-myosin heavy chain (MHC) promoter to overexpress a HS-carrying core protein, syndecan-4, in cardiac myocytes in mice.

Adenovirus-mediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats.

Chronic hypoxic pulmonary hypertension (PH) is associated with vasoconstriction and structural remodeling of pulmonary vessels including narrowing of the arterial lumen and loss of distal functional arteries. To test whether lung overexpression of the angiogenic factor vascular endothelial growth factor (VEGF) is beneficial in hypoxic PH, recombinant adenovirus encoding the human VEGF 165 gene under the control of a cytomegalovirus promoter (Ad. VEGF) or control vector containing no gene in the expression cassette (Ad.

Imbalance between platelet vascular endothelial growth factor and platelet-derived growth factor in pulmonary hypertension. Effect of prostacyclin therapy.

Focal vascular injury and impaired endothelial function are features of pulmonary hypertension (PH) that lead to enhanced platelet endothelial cell interactions. Vascular endothelial growth factor (VEGF) is contained in platelets and released at sites of vascular injury to promote endothelial repair and wound healing in combination with platelet-derived nonspecific mitogens such as platelet-derived growth factor (PDGF). The overall balance between platelet VEGF and PDGF was investigated in 21 patients with primary PH, 8 with secondary PH, and 27 with chronic hypoxemic lung disease (CHLD), as well as in 29 control subjects.

[Effects of 17beta-estradiol on peripheral and coronary vasomotor function in postmenopausal women].

Women appear to be protected, until the menopause, from the development of coronary artery syndromes. This protective effect seems to be due to the beneficial effect of ovarian hormones, in particular oestrogens. A number of potential mechanisms for the protective effect of oestrogens have been proposed.

Heart and lung VEGF mRNA expression in rats with monocrotaline- or hypoxia-induced pulmonary hypertension.

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is upregulated during exposure to hypoxia. In this study, we analyzed heart and lung VEGF mRNA expression and examined pulmonary vascular remodeling as well as myocardial capillary density in two rat models of pulmonary hypertension involving exposure to chronic hypoxia (CH) and treatment with monocrotaline (MCT), respectively. The rats were studied after 0.

Effects of a chronic high-salt diet on large artery structure: role of endogenous bradykinin.

Bradykinin activity could explain the blood pressure increase during NaCl loading in hypertensive animals, but its contribution on vascular structure was not evaluated. We determined cardiac mass and large artery structure after a chronic, 4-mo, high-salt diet in combination with bradykinin B2-receptor blockade by Hoe-140. Four-week-old rats were divided into eight groups according to strain [spontaneously hypertensive rats (SHR) vs.

Comparison of chloroguanide and mephenytoin for the in vivo assessment of genetically determined CYP2C19 activity in humans.

Objectives: The main objective of this study was to examine the relations between chloroguanide (proguanil) and mephenytoin metabolic ratios to determine whether or not chloroguanide could replace mephenytoin as a probe for the indirect in vivo measurement of CYP2C19 activity. An additional objective was to examine the interactions between chloroguanide, omeprazole, and mephenytoin, which are three substrates of CYP2C19.

Methods: Twenty healthy volunteers received 200 mg chloroguanide orally on three separate occasions in an open, randomized-sequence crossover design: once alone, once 2 hours before the oral administration of 100 mg mephenytoin, and once after oral administration for 7 days of 40 mg/day omeprazole.

Acute myocardial infarction in a patient with severe aortic stenosis and normal coronary arteries.

We report a case of acute myocardial infarction occurring in a patient with severe aortic stenosis and left ventricular hypertrophy. A coronary angiogram performed during the acute phase of evolving myocardial infarction excluded coronary obstruction as the cause of acute myocardial infarction in this patient.