Active B-Type Natriuretic Peptide Measured by Mass Spectrometry and Response to Sacubitril/Valsartan.

Background: B-type natriuretic peptide (BNP) immunoassays (BNP) do not differentiate active and inactive forms. Inactive NT-proBNP is used to track heart failure (HF) during treatment with sacubitril/valsartan, which inhibits BNP degradation. Mass spectrometry (MS) may better assess effects of HF treatment on biologically active BNP1-32.

Identification of Emergency Department Patients With Acute Heart Failure at Low Risk for 30-Day Adverse Events: The STRATIFY Decision Tool.

Objectives: No prospectively derived or validated decision tools identify emergency department (ED) patients with acute heart failure (AHF) at low risk for 30-day adverse events who are thus potential candidates for safe ED discharge. This study sought to accomplish that goal.

Background: The nearly 1 million annual ED visits for AHF are associated with high proportions of admissions and consume significant resources.

Eosinophilic myocarditis-an unusual cause of left ventricular hypertrophy.

Eosinophilic myocarditis is a rare condition in which inflammation of the heart results in an infiltrative cardiomyopathy that is often difficult to diagnose in the acute setting. It sometimes presents as left ventricular hypertrophy. The authors present a case of a 79-year-old woman with a history of Non-Hodgkin's lymphoma who presented with acute heart failure with marked left ventricular hypertrophy.

Soluble ST2 as a Diagnostic and Prognostic Marker for Acute Heart Failure Syndromes.

OBJECTIVES: We investigated the association of sST2 with diagnostic and prognostic outcomes and assessed whether it aids B-natriuretic peptide (BNP) in diagnosing and predicting outcomes in emergency department (ED) patients with suspected AHFS. METHODS: We recruited patients who presented to the ED of 3 tertiary hospitals with signs or symptoms of AHFS and met modified Framingham criteria for AHFS. Outcome measures were a final diagnosis of AHFS and 5-and 30-day adverse events.

Stem cell therapy for chronic heart failure: an updated appraisal.

Introduction: Significant advances have been made to understand the mechanisms involved in cardiac cell-based therapies. The early translational application of basic science knowledge has led to several animal and human clinical trials. The initial promising beneficial effect of stem cells on cardiac function restoration has been eclipsed by the inability of animal studies to translate into sustained clinical improvements in human clinical trials.

Low numeracy is associated with increased odds of 30-day emergency department or hospital recidivism for patients with acute heart failure.

Background: More than 25% of Medicare patients hospitalized for heart failure are readmitted within 30 days. The contributions of numeracy and health literacy to recidivism for patients with acute heart failure (AHF) are not known.

Methods And Results: A cohort of patients with acute heart failure who presented to 4 emergency departments between January 2008 and September 2011.

Risk stratification in acute heart failure: rationale and design of the STRATIFY and DECIDE studies.

Background: A critical challenge for physicians facing patients presenting with signs and symptoms of acute heart failure (AHF) is how and where to best manage them. Currently, most patients evaluated for AHF are admitted to the hospital, yet not all warrant inpatient care. Up to 50% of admissions could be potentially avoided and many admitted patients could be discharged after a short period of observation and treatment.

Galectin 3 complements BNP in risk stratification in acute heart failure.

Background: Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure.

Methods: Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial.

Results: Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury.

A comparison of criterion standard methods to diagnose acute heart failure.

The authors sought to compare and contrast the clinical criterion standards currently used in a cohort of emergency department (ED) patients to diagnose acute heart failure syndromes (AHFS). In a prospective observational study of patients with signs and symptoms of AHFS, 3 criterion standards were examined: (1) the treating ED physician's diagnosis; (2) the hospital discharge diagnosis; and (3) a diagnosis based on medical record review by a panel of cardiologists. Using Cohen's kappa (κ) coefficient, the authors assessed agreement and then compared the different standards by repeatedly setting one as the criterion standard and the other two as index tests.

Standardized reporting criteria for studies evaluating suspected acute heart failure syndromes in the emergency department.

Heart failure requiring urgent therapy represents a burgeoning health care burden. Although acute heart failure syndromes are commonly defined as a change in chronic heart failure signs and symptoms requiring urgent therapy, the presentation, development, and response to treatment is highly dependent on individual patient characteristics. This heterogeneity has led to challenges in interpreting widely differing study methods, including eligibility requirements and outcome measures.

Relationship between Uric Acid Levels and Diagnostic and Prognostic Outcomes in Acute Heart Failure.

Objectives: We evaluated the association of plasma uric acid alone and in combination with b-type natriuretic peptide (BNP) for emergency department (ED) diagnosis and 30-day prognosis in patients evaluated for acute heart failure (AHF).

Methods: We prospectively enrolled 322 adult ED patients with suspected AHF. Wilcoxon rank sum test, multivariable logistic regression and likelihood ratio (LR) tests were used for statistical analyses.

Benefits of ambulatory axillary intra-aortic balloon pump for circulatory support as bridge to heart transplant.

Objective: Axillary intra-aortic balloon pump therapy has been described as a bridge to transplant. Advantages over femoral intra-aortic balloon pump therapy include reduced incidence of infection and enhanced patient mobility. We identified the patients who would benefit most from this therapy while awaiting heart transplantation.

Stem cell therapy for cardiac disease: what can be learned from oncology.

Hematopoietic stem cells (HSCs) are the most well-characterized and studied stem cells. They have been used to treat various benign and malignant hematologic disorders. Most stem cell transplant recipients survive more than 5 years without any evidence of their original clinical disease.

Low-risk acute heart failure patients: external validation of the Society of Chest Pain Center's recommendations.

Introduction: Risk-stratification in acute heart failure syndromes (AHFS) is problematic. A recent set of recommendations describes emergency department (ED) patients with AHFS who do not fulfill high-risk criteria and may be good candidates for observation unit (OU) management. The goal of this analysis was to report on the outcomes experienced by ED patients with AHFS who do not have any of these high-risk criteria.

The rationale for an acute heart failure syndromes clinical trials network.

Background: Clinical trials involving novel therapies treating acute heart failure syndromes (AHFS) have shown limited success with regard to both efficacy and safety. As a direct result, outcomes have changed little over time and AHFS remains a disease process associated with largely no change in hospitalization rates (80%), hospital length of stay (median 4.5 days), and in-hospital (4-7%) and 60-day mortality (10%).

Vasopeptidase inhibition: a new direction in cardiovascular treatment.

The development of new antihypertensive agents is becoming even more important. We need better blood pressure control and also agents that treat hypertension as a disease of the vascular endothelium. Recently, it has been shown that blocking the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors reduces blood pressure and decreases the incidence of vascular disease.

ANF elicits phosphorylation of the cGMP phosphodiesterase in vascular smooth muscle cells.

Guanosine 3',5'-cyclic monophosphate (cGMP)-binding, cGMP-specific phosphodiesterase (PDE5) is abundant in vascular smooth muscle, and this enzyme is a potent substrate for cGMP-dependent protein kinase (PKG) in vitro. Binding of cGMP to the allosteric sites of PDE5 is required for this phosphorylation to occur. Vascular smooth muscle cells (VSMC) were used to determine if PDE5 is phosphorylated in intact cells when cGMP is increased.

Multiple enhancer elements mediate induction of c-fos in vascular smooth muscle cells.

Previous work from this and other laboratories has demonstrated that the vasoconstrictor peptide angiotensin II results in hypertrophy of rat aortic smooth muscle cells that is associated with an increase in transcription of the early growth response gene c-fos. To explore the molecular mechanism responsible for c-fos induction in rat aortic smooth muscle cells, we used a series of reporter constructs linked to the chloramphenicol acetyl transferase gene in transient transfection experiments in rat aortic smooth muscle cells. Constructs containing both the serum response element and cAMP response element exhibited a 20-fold increase in chloramphenicol acetyl transferase activity in response to either serum or angiotensin II, whereas no increase was seen in vehicle-treated cells.

Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation.

Elevated levels of endogenous angiotensin can cause hypertensive nephrosclerosis as a result of the potent vasopressor action of the peptide. We have produced by gene targeting mice homozygous for a null mutation in the angiotensinogen gene (Atg-1-). Postnatally, Atg-1- animals show a modest delay in glomerular maturation.

Enhancement of liposome-mediated gene transfer into vascular tissue by replication deficient adenovirus.

For both in vitro and in vivo experiments, especially in vascular cells, an efficient and easy method of gene transfer into this tissue would be extremely useful. Previous methods have either yielded low levels of expression or require complicated manipulation of viral vectors. The goal of this study was to develop an easy, efficient method to introduce unmodified plasmid DNA into vascular tissue.

Low-dose, beta-particle emission from 'stent' wire results in complete, localized inhibition of smooth muscle cell proliferation.

Background: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by medial and/or intimal smooth muscle cell (SMC) proliferation. The objective of this study was investigate the ability of local emission of beta-particles from a 32P-impregnated titanium "stent" wire source to inhibit vascular SMC and endothelial cell proliferation in cell culture and to determine the dose-response characteristics of this inhibition.

Methods And Results: A series of experiments were performed using 0.

Focal adhesion kinase is abundant in developing blood vessels and elevation of its phosphotyrosine content in vascular smooth muscle cells is a rapid response to angiotensin II.

Focal adhesion kinase (FAK) is a structurally unique nonreceptor protein-tyrosine kinase that localizes to focal adhesion plaques. Regulation of its activity has been implicated in diverse signaling pathways, including those mediated by extracellular matrix/integrin interactions, G-protein coupled receptors for mitogenic neuropeptides, and certain oncogene products. To gain evidence for specific processes in which FAK may be involved in vivo, a study was initiated to determine its expression pattern during mouse development.

Role of the tissue renin-angiotensin system in vascular remodeling and smooth muscle cell growth.

In recent years numerous data have given evidence that the tissue renin-angiotensin system may play an equal or perhaps an even more important role than the circulating renin-angiotensin system in numerous physiologic processes. This was first suggested by the observation that the blood pressure lowering effect of angiotension-converting enzyme (ACE) inhibitors correlates better with tissue ACE activity than with plasma ACE activity. In response to hypertension and arterial injury, vascular smooth muscle cells undergo three responses: hypertrophy, hyperplasia, and remodeling.