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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.Intravenous fluids are routinely provided to many hospitalized patients.We conducted a retrospective cohort study of patients admitted with HF to 346 hospitals from 2009 to 2010. We assessed the use of intravenous fluids during the first 2 days of hospitalization. We determined the frequency of adverse in-hospital outcomes. We assessed variation in the use of intravenous fluids across hospitals and patient groups.Among 131,430 hospitalizations for HF, 13,806 (11%) were in patients treated with intravenous fluids during the first 2 days. The median volume of administered fluid was 1,000 ml (interquartile range: 1,000 to 2,000 ml), and the most commonly used fluids were normal saline (80%) and half-normal saline (12%). Demographic characteristics and comorbidities were similar in hospitalizations in which patients did and did not receive fluids. Patients who were treated with intravenous fluids had higher rates of subsequent critical care admission (5.7% vs. 3.8%; p 0.0001), intubation (1.4% vs. 1.0%; p = 0.0012), renal replacement therapy (0.6% vs. 0.3%; p 0.0001), and hospital death (3.3% vs. 1.8%; p 0.0001) compared with those who received only diuretics. The proportion of hospitalizations that used fluid treatment varied widely across hospitals (range: 0% to 71%; median: 12.5%).Many patients who are hospitalized with HF and receive diuretics also receive intravenous fluids during their early inpatient care, and the proportion varies among hospitals. Such practice is associated with worse outcomes and warrants further investigation.

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 characteristi...

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. We used hierarchical logistic regression models to estimate hospital-level risk-standardized rates of inotrope use and risk-standardized in-hospital mortality rates. Results The risk-standardized rates of inotrope use ranged across hospitals from 0.9% to 44.6% (median: 6.3%, interquartile range: 4.3% to 9.2%). We identified various hospital patterns based on the type of agents: dobutamine-predominant (29% of hospitals), dopamine-predominant (25%), milrinone-predominant (1%), mixed dobutamine and dopamine pattern (32%), and mixed pattern including all 3 agents (13%). When studying the factors associated with interhospital variation, the best model performance was with the hierarchical generalized linear models that adjusted for patient case mix and an individual hospital effect (receiver operating characteristic curves from 0.77 to 0.88). The intraclass correlation coefficients of the hierarchical generalized linear models (0.113 for any inotrope) indicated that a noteworthy proportion of the observed variation was related to an individual institutional effect. Hospital rates or patterns of use were not associated with differences in length of stay or risk-standardized mortality rates. Conclusions We found marked differences in the use of inotropic agents for heart failure patients among a diverse group of hospitals. This variability, occurring in the context of little clinical evidence, indicates an urgent need to define the appropriate use of these medications.

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. Hierarchical generalized linear regression models estimated risk-standardized hospital-level rates of inotrope use within 209 hospitals participating in Get With The Guidelines-Heart Failure (GWTG-HF) registry between 2005 and 2011. The association between risk-standardized rates of inotrope use and clinical outcomes was determined. Overall, an inotropic agent was administered in 7691 of 126 564 (6.1%) heart failure hospitalizations: dobutamine 43%, dopamine 24%, milrinone 17%, or a combination 16%. Patterns of inotrope use were stable during the 7-year study period. Use of inotropes varied significantly between hospitals even after accounting for patient and hospital characteristics (median risk-standardized hospital rate, 5.9%; interquartile range, 3.7%–8.6%; range, 1.3%–32.9%). After adjusting for case-mix and hospital structural differences, model intraclass correlation indicated that 21% of the observed variation in inotrope use was potentially attributable to random hospital effects (ie, institutional preferences). Hospitals with higher risk-standardized inotrope use had modestly longer risk-standardized length of stay ( P =0.005) but had no difference in risk-standardized inpatient mortality ( P =0.12) Conclusions— Use of intravenous inotropic agents during hospitalization for heart failure varies significantly among US hospitals even after accounting for patient and hospital factors.

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 0.5, 1, 3, 15, and 30 days of exposure to 10% O2 or 1, 6, and 30 days after a subcutaneous MCT injection (60 mg/kg). Both CH and MCT induced pulmonary hypertension and hypertrophy of the right ventricle (RV) with increased RV weight and atrial natriuretic peptide mRNA expression. VEGF mRNA expression as assessed by Northern blot analysis was potently induced after 12 h of hypoxia in both the right and left ventricles. After prolonged exposure to hypoxia, VEGF mRNA returned to baseline in the left ventricle (LV) but remained increased in the RV, where it peaked after 30 days. In MCT rats, VEGF mRNA was unchanged in the LV but decreased by 50% in the RV and by 90% in the lungs after 30 days. VEGF mRNA remained unchanged in the lungs from CH rats. Pulmonary vascular remodeling was more pronounced in MCT than in CH rats. The number of capillaries per RV myocyte was increased in rats exposed to 30 days of hypoxia, whereas it remained unchanged in MCT rats despite a similar degree of RV hypertrophy. Our results suggest that the sustained increase in VEGF expression in the hypertrophied RV during CH may account for the increased number of capillaries per myocyte. In contrast, reduced VEGF expression in the lungs and RV of MCT rats may aggravate pulmonary vascular remodeling and compromise RV myocardial perfusion.

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. Wistar-Kyoto (WKY) rats], diet (0.4 vs. 7% NaCl), and treatment (Hoe-140 vs. placebo). In WKY rats, a high-salt diet significantly increased intra-arterial blood pressure with minor changes in arterial structure independently of Hoe-140. In SHR, blood pressure remained stable but 1) the high-salt diet was significantly associated with cardiovascular hypertrophy and increased arterial elastin and collagen, and 2) Hoe-140 alone induced carotid hypertrophy. A high-salt diet plus Hoe-140 acted synergistically on carotid hypertrophy and elastin content in SHR, suggesting that the role of endogenous bradykinin on arterial structure was amplified in the presence of a high-salt diet.

Background: Although loop diuretics are frequently used for patients with heart failure (HF), little is known about the variation in patterns of diuretic therapy in US hospitals. We sought to describe such treatment patterns among a diverse group of hospitals. Methods: We studied HF hospitalizations occurring during 2009-10 in Premier Inc. hospitals participating in a collaborative project to pool administrative and charge data, which includes information about drug types, average daily dose, and duration of therapy. We excluded hospitals with less than 25 HF hospitalizations. For ease of comparison, all diuretic doses were converted to bioequivalent doses of intravenous (IV) furosemide: 40mg IV furosemide ∼ 80mg oral furosemide ∼ 20mg (oral or IV) torsemide ∼ 1mg (oral or IV) bumetanide. Summary statistics were calculated. Results: Among 366 studied hospitals (264,675 HF hospitalizations), use of any loop diuretic had an interquartile range (IQR) from 92% to 96% (median: 94%). At the hospital level, the average daily dose IQR varied from 45mg to 64 mg (median: 55 mg) and the median duration of therapy was 4 days (IQR: 4 to 4; median: 4), as was the median length of stay. The IQR for use of furosemide varied from 89% to 94% (median: 92%), and its median average daily dose had an IQR from 40mg to 60 mg (median: 53 mg). Hospital use of bumetanide had an IQR from 2% to 11%, and hospital use of torsemide had an IQR from 0% to 4% (medians of 5% and 1%, respectively). The variation in median average daily dose for bumetanide and torsemide was greater than for furosemide (bumetanide IQR: 79mg to 127 mg, with median of 89 mg; torsemide IQR: 53mg to 120 mg, with median of 80 mg). Use of IV diuretics on the last day before home discharge had an IQR from 16% to 33% (median: 24%) across hospitals. Conclusion: US hospitals administer loop diuretics, particularly furosemide, to the vast majority of HF inpatients. The duration and daily dosage of therapy was similar across most hospitals. In contrast, a minority of hospitals used bumetanide and torsemide for several patients. The daily dosage of these agents showed more marked variation. We observed a high rate of intravenous diuretic use on the last day of hospitalization, with considerable variation across hospitals.

To the Editor: Diuretics are a mainstay of treatment in both chronic and acute decompensated heart failure (HF). Studies during the 1990s and early 2000s show that roughly 90% of HF patients receive at least 1 class of diuretics, particularly a loop diuretic, for management of chronic ([1,2][1]) or

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.

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. Mice expressing the transgene (alpha MHC-S4) demonstrated a significant increase in nitric oxide (NO) release in the coronary effluent in response to fibroblast growth factor 2 (FGF2, 1 microg/mL) administration despite similar expression levels of NO synthase genes II and III (iNOS and eNOS, respectively). In vitro studies of coronary microvessels derived from alpha MHC-S4 mice demonstrated increased relaxation response to FGF2 compared to control mice. At the same time, vasodilator response to adenosine diphosphate (ADP) was significantly impaired in alpha MHC-S4 mice-derived microvessels. Addition of exogenous HS to microvessels derived from control mice enhanced FGF2-induced vasodilation while inhibiting ADP-induced vasomotion. The vasomotor activity of the endothelial receptor-independent agent (A23187) and the endothelium-independent agent (sodium nitroprusside) was not affected by heparan sulfate. These results demonstrate that alterations in HS production have a profound and heterogeneous effect on endothelial receptor-dependent vasodilators and point to a novel role of the HS matrix in regulation of microvascular homeostasis.

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 (PIP2)-dependent PKC-α 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. Several transgenic mice lines expressing syndecan-4 cDNA under control of human endothelial nitric oxide (NO) synthase (eNOS) promoter were generated. Exogenous syndecan-4 was mainly expressed in the heart, brain, and lungs. In particular, the heart demonstrated the greatest increase in the ratio of transgenic-to-native syndecan-4 gene expression. Vessels from the eNOS-syndecan-4 mice demonstrated more pronounced vasodilation to FGF2 but not to VEGF-A165, sodium nitroprusside, and A 23187 compared with wild-type mice. To elucidate the mechanism of this effect, we measured NO release from primary cardiac endothelial cells isolated from transgenic or wild-type adult mice. Cells from the eNOS-syndecan-4 transgenic mice had a significant increase in FGF2- and VEGF-A165-induced NO release compared with endothelial cells from the wild-type mice. However, the absolute magnitude of this increase was higher for FGF2 than VEGF-A165. In conclusion, enhanced syndecan-4 expression in mouse cardiac endothelial cells results in preferential augmentation of FGF2 but not VEGF-A165-induced NO release.

Concern about rising cost has focused attention on altering hospital practices to reduce expenses. We examined variation in use of the ICU, a high cost setting, for heart failure (HF) admissions. We identified 188,216 HF discharges from 341 hospitals in the 2009-10 Premier Perspective database. We