Effect of Optison on pulmonary artery systolic pressure and pulmonary vascular resistance.

Ultrasound contrast agent safety has received recent attention based on reports of associated serious adverse events. The US Food and Drug Administration requested this postmarketing study of the effects of Optison on pulmonary hemodynamics. The aim of this study was to compare Optison and a placebo for effects on pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) during right-sided cardiac catheterization.

Applications of fluorescence spectroscopy for predicting percent wastewater in an urban stream.

Dissolved organic carbon (DOC) is a significant organic carbon reservoir in many ecosystems, and its characteristics and sources determine many aspects of ecosystem health and water quality. Fluorescence spectroscopy methods can quantify and characterize the subset of the DOC pool that can absorb and re-emit electromagnetic energy as fluorescence and thus provide a rapid technique for environmental monitoring of DOC in lakes and rivers. Using high resolution fluorescence techniques, we characterized DOC in the Tualatin River watershed near Portland, Oregon, and identified fluorescence parameters associated with effluent from two wastewater treatment plants and samples from sites within and outside the urban region.

The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial.

Background: Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are characteristic of systolic heart failure and might be improved by a new therapeutic class, cardiac myosin activators. We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure.

Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study.

Background: Decreased systolic function is central to the pathogenesis of heart failure in millions of patients worldwide, but mechanism-related adverse effects restrict existing inotropic treatments. This study tested the hypothesis that omecamtiv mecarbil, a selective cardiac myosin activator, will augment cardiac function in human beings.

Methods: In this dose-escalating, crossover study, 34 healthy men received a 6-h double-blind intravenous infusion of omecamtiv mecarbil or placebo once a week for 4 weeks.

Cardiac toxicity screening by echocardiography in healthy volunteers: a study of the effects of diurnal variation and use of a core laboratory on the reproducibility of left ventricular function measurement.

Background: In investigational medicinal products testing centers (IMP), reliable methods for monitoring early signs of cardiotoxicity of a potential new drug in healthy volunteers are essential. This study examines what levels of left ventricular ejection fraction (LVEF) variance can be achieved with two-dimensional echocardiography (2DE) in a core laboratory versus a site laboratory. Diurnal variability of LVEF and diastolic parameters were also reviewed.

A retrospective comparison of mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent.

Objectives: To compare acute mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent (UCA).

Background: Because of serious cardiopulmonary reactions reported immediately after administration of perflutren-containing UCAs, the FDA required a black box safety warning for this class of agents, including perflutren protein-type A microspheres injectable suspension.

Methods: This study used the largest hospital service-level database in the U.

Ultrasound contrast agents: balancing safety versus efficacy.

In October, 2007, the FDA issued a new 'black box' warning, several new disease state contraindications and a mandated 30-min post-procedure monitoring period for the ultrasound contrast agents Definity (perflutren lipid microsphere injectable suspension, Lantheus Medical Imaging, North Billerica, MA, USA) and Optison (perflutren protein type A microspheres for injectable suspension, GE Healthcare, Buckinghamshire, UK). These labeling changes were largely secondary to reports of 4 patient deaths, and approximately 190 other 'serious cardiopulmonary reactions' that were temporally related but not clearly causally attributable to Definity administration. Contrast agent use in the US plummeted in the immediate aftermath of this FDA action, with many hospitals, physician offices and outpatient imaging centers suspending contrast echocardiography altogether.

Thinking outside the "box"-the ultrasound contrast controversy.

On October 10, 2007, the U.S. Food and Drug Administration (FDA) announced a new "black box" warning for the perflutren-containing ultrasound contrast agents, contraindicating their use in patients with acute coronary syndromes, acute myocardial infarction, and worsening or clinically unstable heart failure.

Pulmonary hemodynamic effects of dipyridamole infusion in patients with normal and elevated pulmonary artery systolic pressure receiving PB127.

Background: Intravenous administration of microspheres used as ultrasound contrast agents may potentially alter pulmonary hemodynamics. PB127 (POINT Biomedical Corp., San Carlos, CA) is an investigational ultrasound perfusion-imaging agent used in conjunction with dipyridamole to diagnose coronary artery disease.

Left atrial size is a poor predictor of pathology in the older patient: preliminary observations.

Objective: The goal of this study was to determine the relationship between left atrial (LA) size and pathology in humans.

Methods: We evaluated 14 patients (age 60 +/- 14 years, range 25-77, 9 males) who had died at our hospital. Eight patients were in sinus rhythm, 3 had paroxysmal atrial fibrillation (PAF), and 3 were in established atrial fibrillation (AF).

Myocardial contrast echocardiography (MCE) with triggered ultrasound does not cause premature ventricular complexes: evidence from PB127 MCE studies.

Previous studies suggest that myocardial contrast echocardiography using high mechanical index triggered ultrasound can be associated with increased frequency of the premature ventricular complex (PVC). However, this association has not been systematically examined. PB127 (Point Biomedical Corp, San Carlos, Calif) is a novel microsphere designed for evaluation of myocardial perfusion with ultrasound.

Elevated serum levels of soluble interleukin-2 receptor, neopterin and beta-2-microglobulin in idiopathic dilated cardiomyopathy: relation to disease severity and autoimmune pathogenesis.

Background: It has not been assessed whether high levels of soluble interleukin 2 receptor (sIL-2R), neopterin and beta-2 microglobulin in idiopathic dilated cardiomyopathy reflect heart failure severity and/or an active autoimmune process. The aim of this study was to relate serum levels of these markers to clinical and autoimmune features.

Methods: We studied 60 patients with idiopathic dilated cardiomyopathy, 67 controls with ischemic heart failure and 34 normals.

Transesophageal echocardiographic (TEE) evaluation of intracardiac and pericardial masses.

Transesophageal echocardiography has assisted the detection of intracardiac masses and, in certain cases, aided our ability to define the specific type of mass. This technique, when coupled with three-dimensional imaging, may help to define infiltration of the wall. TEE aids in the intraoperative management of cardiac tumors.

Usefulness of stroke distance by echocardiography as a surrogate marker of cardiac output that is independent of gender and size in a normal population.

Left ventricular outflow tract stroke distance (SD) can be measured using pulsed-wave Doppler echocardiography, and is independent of body size. Moreover, persons with structurally normal hearts (heart rate < 55 beats/min) had SD > 0.18 m, and those with a heart rate > 95 beats/min had SD < 0.

Cardiac autoimmunity in HIV related heart muscle disease.

Objective: To assess the frequency of circulating cardiac specific autoantibodies in HIV positive patients with and without echocardiographic evidence of left ventricular dysfunction.

Subjects: 74 HIV positive patients including 28 with echocardiographic evidence of heart muscle disease, 52 HIV negative people at low risk of HIV infection, and 14 HIV negative drug users who had all undergone non-invasive cardiac assessment were studied along with a group of 200 healthy blood donors.

Results: Cardiac autoantibodies detected by indirect immunofluorescence (serum dilution 1/10) were more common in the HIV positive patients (15%), particularly the HIV heart muscle disease group (21%), than in HIV negative controls (3.

Cardiogenic shock secondary to mitral stenosis treated by balloon mitral valvuloplasty.

Percutaneous balloon mitral valvuloplasty is a well-established elective treatment for mitral stenosis in selected patients; it has been used to treat cardiogenic shock secondary to aortic stenosis but has not been previously used for cardiogenic shock secondary to mitral stenosis. We describe a case of cardiogenic shock secondary to severe mitral stenosis, treated by balloon mitral valvuloplasty.

Familial dilated cardiomyopathy: cardiac abnormalities are common in asymptomatic relatives and may represent early disease.

Objectives: This study sought to determine whether early disease is identifiable in asymptomatic relatives of patients with dilated cardiomyopathy (DCM) by means of noninvasive cardiologic assessment.

Background: DCM is diagnosed on the basis of advanced heart failure, where cardiac dilation and impaired contractility are recognized in the absence of a recognized etiology (World Health Organization criteria). However, initial clinical presentation may be with severe complications: thromboembolism, arrhythmia or sudden death.

Usefulness of signal-averaged electrocardiography in evaluation of idiopathic-dilated cardiomyopathy in families.

Family studies have confirmed that familial dilated cardiomyopathy is common and that a large proportion of relatives have mild left ventricular enlargement and therefore potentially early disease. Previous studies have shown that patients with idiopathic dilated cardiomyopathy have abnormalities of the signal-averaged electrocardiogram (ECG). We assessed the usefulness of analysis of the signal-averaged ECG in the evaluation of familial dilated cardiomyopathy.

Increased ventricular sialylation in patients with heart failure secondary to ischemic heart disease.

Background: Elevated serum sialic acids are associated with increased cardiovascular mortality, but sialic acid levels have not been studied in cardiac tissue.

Methods: Myocardial samples were obtained at the time of transplantation from 23 patients (age 54 +/- 12 years) with heart failure secondary to ischemic heart disease and 16 patients (age 51 +/- 7 years) with idiopathic dilated cardiomyopathy (DCM). A control group comprised postmortem samples obtained from 14 patients (age 70 +/- 5 years) who died of non-cardiovascular causes.

Human chagasic disease is not associated with an antiheart humoral response.

An inflammatory cardiomyopathy occurs in humans with chronic Trypanosoma cruzi infection (Chagas' disease). This study finds that T. cruzi infection is not associated with the production of cardiac-specific autoantibodies in humans with cardiac manifestations.

Lack of T cell response to cardiac myosin and a reduced response to PPD in patients with idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDCM) is the main cause of cardiac transplantation in young adults in the 20-40 years age group in the Western world. Recent evidence supports a possible role for autoimmune pathogenesis in IDCM and it has been suggested that T cells could mediate the disease. Cardiac myosin is one of the putative autoantigens recognized by antibodies from patients with IDCM, but T cell responses to cardiac myosin have not previously been assessed.

Heart rate variability in idiopathic dilated cardiomyopathy: relation to disease severity and prognosis.

Objective: To assess the clinical importance of heart rate variability (HRV) in patients with idiopathic dilated cardiomyopathy (DCM).

Patients And Methods: Time domain analysis of 24 hour HRV was performed in 64 patients with DCM, 19 of their relatives with left ventricular enlargement (possible early DCM), and 33 healthy control subjects.

Results: Measures of HRV were reduced in patients with DCM compared with controls (P < 0.

Circulating cardiac-specific autoantibodies as markers of autoimmunity in clinical and biopsy-proven myocarditis. The Myocarditis Treatment Trial Investigators.

Aim: Myocarditis and dilated cardiomyopathy may be phases of an organ-specific autoimmune disease of the myocardium. To provide evidence for autoimmune involvement in myocarditis, cardiac autoantibodies were detected in patient sera from the Myocarditis Treatment Trial.

Methods And Results: Cardiac antibody status was assessed by indirect immunofluorescence and by anti-alpha-myosin enzyme-linked immunosorbent assay in 53 patients from the Myocarditis Treatment Trial (35 males, aged 42 +/- 15 years); all had clinical myocarditis, but only 24 were classified as having histological myocarditis (Dallas criteria).

Cardiac autoantibodies in dilated cardiomyopathy become undetectable with disease progression.

Objective: To determine the relation of cardiac autoantibody and disease status in a consecutive series of patients with dilated cardiomyopathy by prospective antibody testing at diagnosis and at follow up.

Methods: Antibody status was assessed by indirect immunofluorescence in 110 patients with dilated cardiomyopathy (85 male, mean (SD) age 44 (13) years) at diagnosis and at follow up (mean (SD) 14 (12) months); in 57 of them cardiac specific anti-alpha myosin antibody titres were also measured by an enzyme-linked immunosorbent assay (ELISA). Patients underwent complete evaluation at diagnosis and clinical and non-invasive assessment at follow up, including exercise testing with maximal oxygen consumption measurements.