Effects of the adenosine A1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: results from PROTECT (Placebo-Controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function).

Objectives: This study sought to assess the effects of rolofylline on renal function in patients with acute heart failure (AHF) and renal dysfunction randomized in PROTECT (Placebo-Controlled Randomized Study of the Selective A(1) Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function).

Background: Small studies have indicated that adenosine A(1) receptor antagonists enhance diuresis and may improve renal function in patients with chronic heart failure or AHF.

Methods: A total of 2,033 patients with AHF, volume overload, estimated creatinine clearance between 20 and 80 ml/min, and elevated natriuretic peptide levels were randomized (2:1) within 24 h of hospital presentation to rolofylline 30 mg/day or intravenous placebo for up to 3 days.

Low lymphocyte ratio as a novel prognostic factor in acute heart failure: results from the Pre-RELAX-AHF study.

Background: Previous studies have suggested that a lower lymphocyte ratio (Ly%) in the white blood cell (WBC) differential count is related to worse outcomes in patients with acute heart failure (AHF) and other cardiovascular disorders.

Methods: In the Pre-RELAX-AHF study, 234 patients with AHF, systolic blood pressure >125 mm Hg and brain natriuretic peptide ≥350 pg/ml or equivalent were randomized to 1 of 4 intravenous doses of relaxin or placebo and followed up for 6 months following randomization. Complete blood count and differential were performed by a central laboratory at baseline and then daily to day 5 and on day 14.

Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure.

Background: Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1-receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure.

Acute heart failure clinical drug development: from planning to proof of activity to phase III.

Over the last decades, attempts to develop new therapies for acute heart failure (AHF) have largely failed. Limitations in understanding the pathophysiology of AHF, its natural history, the effects of current therapies, the properties of new agents, and, importantly, study designs and execution have contributed to these disappointing results. We propose a novel approach for the development of new agents for AHF.

Haemodynamic effects of rolofylline in the treatment of patients with heart failure and impaired renal function.

Aims: The direct effects of adenosine A1 receptor antagonists on haemodynamic parameters in patients with acute heart failure (HF) remain largely unknown.

Methods And Results: We evaluated the haemodynamic effects of the AA(1)RA rolofylline in 59 HF patients with concomitant renal impairment (estimated creatinine clearance 20-80 mL/min). Placebo or rolofylline 30 mg was administered as a 4 h infusion followed by intravenous (i.

Dyspnoea and worsening heart failure in patients with acute heart failure: results from the Pre-RELAX-AHF study.

Aims: Although dyspnoea is the most common cause of admission for acute heart failure (AHF), more needs to be known about its clinical course and prognostic significance.

Methods And Results: The Pre-RELAX-AHF study randomized 232 subjects with AHF to placebo or four doses of relaxin and evaluated early (6-24 h Likert scale) and persistent [change in visual analogue scale area under the curve (VAS AUC) through Day 5] dyspnoea relief. Worsening heart failure (WHF) was defined as worsening AHF signs and symptoms requiring additional therapy.

A randomized controlled trial of the safety and promise of cognitive-behavioral therapy using imaginal exposure in patients with posttraumatic stress disorder resulting from cardiovascular illness.

Objective: We investigated the physical safety of cognitive-behavioral therapy (CBT) utilizing imaginal exposure in patients who suffered from posttraumatic stress disorder (PTSD) following a life-threatening cardiovascular event.

Method: In this phase I, prospective, single-blind trial conducted from April 2006 through April 2008, we randomly assigned 60 patients to receive either 3 to 5 sessions of imaginal exposure therapy (experimental group) or 1 to 3 educational sessions only (control group). Criteria for PTSD and other mental health disorders were evaluated according to DSM-IV using the full Structured Clinical Interview for DSM-IV (SCID).

Dyspnoea in patients with acute heart failure: an analysis of its clinical course, determinants, and relationship to 60-day outcomes in the PROTECT pilot study.

Aims: Dyspnoea is the most common symptom leading to hospitalization for acute heart failure (AHF). Its early and persistent relief is an important goal of therapy, but little is known about its course, determinants, and prognostic significance.

Methods And Results: In a post hoc analysis, we studied changes in dyspnoea and in-hospital course in 303 subjects with AHF enrolled in the PROTECT pilot trial.

Design and rationale of the PROTECT study: a placebo-controlled randomized study of the selective A1 adenosine receptor antagonist rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function.

Background: Current treatment for acute decompensated heart failure (ADHF) is associated with incomplete resolution of symptoms and signs, recurrent symptoms of heart failure in-hospital and after discharge and high mortality. Studies have consistently demonstrated an association between worsening renal function in ADHF and adverse outcomes. Adenosine A(1) receptor antagonists, such as rolofylline, appear in preliminary studies to produce potentially beneficial effects on natriuresis, diuresis, renal blood flow, and glomerular filtration rate.

Patterns of leukocyte counts on admissions for acute heart failure--presentation and outcome--results from a community based registry.

Objective: To determine the correlation between differential white blood cell (WBC) count and characteristics and outcome of acute heart failure (AHF) syndromes.

Background: Previous studies suggested that different white blood cell count patterns are related to outcome in patients with heart failure (HF) and other cardiovascular disorders.

Methods: Data from all qualifying AHF admissions to a city hospital (n=340) was prospectively collected.

Physician-determined worsening heart failure: a novel definition for early worsening heart failure in patients hospitalized for acute heart failure--association with signs and symptoms, hospitalization duration, and 60-day outcomes.

Objectives: To evaluate physician-determined worsening heart failure (PD-WHF) in patients admitted with acute heart failure (AHF).

Methods: The PROTECT pilot study evaluated rolofylline, an adenosine A(1) receptor antagonist, versus placebo in patients with AHF and renal impairment. Signs and symptoms of heart failure (HF) and diuretic administration were prospectively recorded daily for 7 days and patients were followed for 60 days.

Early worsening heart failure in patients admitted for acute heart failure: time course, hemodynamic predictors, and outcome.

Background: The most common outcome currently assessed in acute heart failure trials (AHF) is dyspnea improvement. Worsening hear failure (WHF) is a new outcome measure that incorporates failure to improve or recurrent symptoms of AHF requiring rescue intravenous therapy, mechanical circulatory or ventilatory support, or readmission because of AHF, occurring within 30 days of AHF admission.

Methods And Results: Retrospective data analysis of 120 patients with AHF requiring hemodynamic monitoring who enrolled in the placebo arm of 2 prospective randomized studies.

Early worsening heart failure in patients admitted with acute heart failure--a new outcome measure associated with long-term prognosis?

A major limitation in acute heart failure (AHF) research has been the lack of an outcome measure paralleling re-infarction in acute coronary syndromes. The aim of the present study was to assess the time course, prognostic factors and outcome of early worsening heart failure (WHF) in patients admitted for AHF to a community hospital. All AHF admissions between December 2003 and March 2004 in a regional medical center were recorded.

Rapid clinical assessment of patients with acute heart failure: first blood pressure and oxygen saturation--is that all we need?

Unlabelled: The risk stratification of patients with acute heart failure (AHF) has been addressed repeatedly in recent years. Low oxygen saturation (SaO2) and systolic blood pressure (SBP) are signs of impending respiratory and circulatory failure that can be obtained quickly in patients with AHF.

Methods: Admissions for AHF (340 patients) in a city hospital were recorded and patients were followed for symptoms of heart failure, re-admission and mortality for 6 months.

Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study.

Background: Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on symptom relief, other clinical outcomes, and safety.

The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment.

Background: Rolofylline, an adenosine A(1) receptor antagonist, facilitates diuresis and preserves renal function in patients with acute heart failure (AHF) with renal impairment. Although not powered around any specific hypothesis, this pilot study was designed to identify an efficacious dose while refining inclusion criteria and end points.

Methods: A total of 301 patients hospitalized for AHF with an estimated creatinine clearance of 20 to 80 mL/min and elevated natriuretic peptide levels were enrolled within 24 hours of presentation to placebo or rolofylline 10, 20, or 30 mg administered as 4-hour infusions for 3 days in addition to intravenously administered loop diuretics.

Hyponatraemia in acute heart failure is a marker of increased mortality but not when associated with hyperglycaemia.

Unlabelled: Previous studies suggest that hyponatraemia is a marker of neurohormonal activation and increased mortality in patients with acute heart failure (AHF). Although diabetes is a common co-morbidity in heart failure, no prior study has considered the impact of serum glucose on this relationship.

Methods: Over four consecutive months we prospectively registered all patients admitted due to AHF.

The association of the ankle-brachial index with incident coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study, 1987-2001.

Background: Peripheral arterial disease (PAD), defined by a low ankle-brachial index (ABI), is associated with an increased risk of cardiovascular events, but the risk of coronary heart disease (CHD) over the range of the ABI is not well characterized, nor described for African Americans.

Methods: The ABI was measured in 12186 white and African American men and women in the Atherosclerosis Risk in Communities Study in 1987-89. Fatal and non-fatal CHD events were ascertained through annual telephone contacts, surveys of hospital discharge lists and death certificate data, and clinical examinations, including electrocardiograms, every 3 years.

Kidney function and risk of peripheral arterial disease: results from the Atherosclerosis Risk in Communities (ARIC) Study.

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular disease, but its association with peripheral arterial disease (PAD) is unclear. With the use of data from the Atherosclerosis Risk in Communities (ARIC) Study, 14,280 middle-aged adults were categorized on the basis of estimated GFR >/=90, 60 to 89, and 15 to 59 ml/min per 1.73 m(2) for normal kidney function, mildly decreased kidney function, and stages 3 to 4 CKD, respectively.

Clinical significance of a high ankle-brachial index: insights from the Atherosclerosis Risk in Communities (ARIC) Study.

Background: The clinical significance of a high ankle-brachial index (ABI), defined by the associated risk factor burden and ischemic risk, is largely unknown.

Methods: Using data from the Atherosclerosis Risk in Communities Study, we categorized 14,777 participants into normal (ABI between 0.9 and 1.

The reliability of the ankle-brachial index in the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS).

Background: A low ankle-brachial index (ABI) is associated with increased risk of coronary heart disease, stroke, and death. Regression model parameter estimates may be biased due to measurement error when the ABI is included as a predictor in regression models, but may be corrected if the reliability coefficient, R, is known. The R for the ABI computed from DINAMAP readings of the ankle and brachial SBP is not known.

Risk factors for peripheral arterial disease incidence in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.

Background: Some risk factors for peripheral arterial disease (PAD) have been identified, but little information is available on PAD risk factors in individuals with diabetes.

Methods: Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we assessed the relation of traditional and non-traditional risk factors with the risk of PAD in 1651 participants with diabetes, but not PAD, at baseline. Incident PAD was defined as an ankle-brachial index (ABI)<0.

Have studies of urinary tract infection and preterm delivery used the most appropriate methods?

Published investigations of the association between urinary tract infection (UTI) and preterm delivery used logistic regression or chi-squared tests. Because both exposure and outcome are time dependent, these methods were not optimal and did not account for person-time under observation, potentially an important feature given the variability of women's entry to prenatal care as well as of gestational lengths. Previous researchers probably classified as exposed some women whose UTI occurred after their pregnancies exceeded 37 weeks.