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Guidelines have rather quickly assumed a central role in health care delivery in the U.S. They have become the foundation on which performance measures are built and, therefore, a major player in assessing the quality of care provided by individuals and institutions, the ramifications of which involve reputation, reimbursement, and litigation. We are concerned, however, that in our enthusiasm for collectively endorsing these guidelines, we are marginalizing the importance of physician judgment and inadvertently risking the conversion of guidelines into “cookbooks.” We believe that this viewpoint, while unequivocally acknowledging the fundamental importance of guidelines, simultaneously provides a critically important perspective on the potential for misuse of both guidelines and performance measures. Further, we hope that publication of this viewpoint will help temper enthusiasm for overzealous conversion of guidelines into performance measures, thereby restoring the vital role of physician judgment and insight into patient management. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to evaluate the dose-dependent effects of adenosine A1-receptor blockade on diuresis and renal function in patients with acute decompensated heart failure (ADHF) and renal impairment or diuretic resistance. Background: Intravenous loop diuretics are the mainstay of therapy for patients with ADHF. Treatment, however, may be complicated by diuretic resistance and/or worsening renal function. Methods: We carried out a pair of randomized, double-blind, placebo-controlled, proof-of-concept studies in 2 clinically challenging ADHF populations. Results: In the ADHF protocol, 146 patients with volume overload and an estimated creatinine clearance (CrCl) of 20 to 80 ml/min were randomized to placebo or 1 of 4 doses of KW-3902 (rolofylline) infused over 2 h daily for up to 3 days. On day 1, KW-3902 monotherapy increased urine output during the first 6 h (445, 531, 631, and 570 ml in the 2.5-, 15-, 30-, and 60-mg groups, respectively) compared with placebo (374 ml; p = 0.02). On day 2, serum creatinine decreased in all KW-3902 groups and increased with placebo (p = 0.04). By day 4 or day of discharge if earlier, intravenous furosemide administration tended to be lower in the KW-3902 groups compared with placebo (p = 0.10). In the diuretic-resistant protocol, 35 patients with an average CrCl of 34 ml/min were randomized to a single infusion of placebo, 10, 30, or 60 mg of KW-3902. Compared with placebo, KW-3902 increased hourly urine volume and estimated CrCl with peak effects occurring at 2 to 3 h and at 24 h, respectively. Adverse events were not different between placebo and KW-3902. Conclusions: In patients with ADHF and volume overload, KW-3902, an adenosine A1-receptor antagonist, enhances the response to loop diuretics and may have a renal protective effect. [Copyright &y& Elsevier]

There has been ongoing controversy as to whether aspirin should be used in patients with chronic heart failure (CHF). The argument for aspirin is that many patients have underlying coronary disease, and aspirin prevents reinfarction and other vascular events. Arguments against the routine use of aspirin are that many CHF patients do not have underlying coronary disease, and that the benefit of aspirin lessens after the first 6 to 12 months after infarction. Also, several analyses suggest that aspirin may actually worsen outcomes in CHF patients, possibly because it inhibits prostaglandins, with resulting adverse hemodynamic and renal effects. Two recent prospective randomized studies have found that aspirin is associated with more frequent hospitalizations for worsening heart failure, although it did not have an adverse effect on vascular events. These results suggest that aspirin should not be routinely used in CHF patients and be avoided in those with refractory CHF, but that it may be beneficial in patients with recent infarction or multiple vascular risk factors. [Copyright &y& Elsevier]

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 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: Small studies have indicated that adenosine A1 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. Creatinine was measured daily until discharge or day 7 and on day 14. Persistent worsening renal function was defined as an increase in serum creatinine ≥0.3 mg/dl at both days 7 and 14, or initiation of hemofiltration or dialysis or death by day 7. Results: At baseline, mean ± SD estimated creatinine clearance was 51.0 ± 20.5 ml/min in the placebo group and 50.4 ± 20.0 ml/min in the rolofylline group. Changes in creatinine and estimated creatinine clearance were similar between placebo- and rolofylline-treated patients during hospitalization and at day 14. After 4 days, mean body weight was reduced by 2.6 and 3.0 kg in placebo and rolofylline patients, respectively (p = 0.005). Persistent worsening renal function occurred in 13.7% of the placebo group and 15.0% of the rolofylline group (odds ratio vs. placebo: 1.11 [95% confidence interval: 0.85 to 1.46]; p = 0.44). Conclusions: In this large, phase III clinical trial, the adenosine A1 receptor antagonist rolofylline did not prevent persistent worsening renal function in AHF patients with volume overload and renal dysfunction. (A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function [PROTECT-1], NCT00328692; and [PROTECT-2], NCT00354458) [Copyright &y& Elsevier]

Objectives: The study sought to investigate the clinical correlates and prognostic role of anemia and changes in hemoglobin in patients hospitalized for acute decompensated heart failure (AHF). Background: Anemia is related to a poor outcome in patients with heart failure. In addition, an increase in hemoglobin during hospitalization might be a sign of effective decongestion and therefore related to improved outcome. Methods: This is a post hoc analysis of the 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) study in 1,969 patients with AHF and mild to moderate impaired renal function. Hemoglobin levels were measured daily for the first 4 days and at day 7. The endpoint was 180-day all-cause mortality. Results: Anemia at baseline was observed in 50.3% of the patients. During follow-up, 359 patients (18.2%) died. Hemoglobin increased in 69.1% and was associated with a better renal function at baseline and more weight loss, but was associated with a deterioration of renal function (p = 0.01), whereas total dose diuretics was lower in patients with hemoconcentration (p < 0.01). Interaction analysis showed that greater weight loss and better baseline renal function were associated with a more rapid increase in hemoglobin concentration (p < 0.01 for both). The absolute change in hemoglobin (g/dl) independently predicted outcome (hazard ratio: 0.66; 95% confidence interval: 0.51 to 0.86; p = 0.002), whereas baseline hemoglobin levels did not. Conclusions: Patients with AHF and preserved renal function are decongested better, as shown by an increase in hemoglobin. A rapid increase in hemoglobin during the first week is independently associated with a favorable outcome, despite a slight decrease in renal function. [ABSTRACT FROM AUTHOR]

This paper details the substance and recommendations arising from a meeting convened by the National Heart, Lung, and Blood Institute in August 2009, to assess the challenges and opportunities of emergency department management of acute heart failure syndrome (AHFS). The assembled faculty represented a large cross section of medical professionals spanning the medical management continuum of patients presenting with acute heart failure and included heart failure cardiologists, emergency physicians, laboratory medicine specialists, nurses, and bench scientists. Their recommendations include proposals regarding the design and conduct of emergency department-based clinical trials, suggestions regarding the development of improved methods for early detection and monitoring of AHFS, and potential needs for expanding translational and applied AHFS focused research and biotechnology. We anticipate that this review will serve as a starting point for future investigations across the spectrum of funding sources. [Copyright &y& Elsevier]

Objectives: The ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) determined that treatment with amlodipine, lisinopril, or doxazosin was not superior to thiazide-like diuretic (chlorthalidone) in preventing coronary heart disease (CHD) or other cardiovascular events. This subanalysis examines baseline prevalence and in-trial incidence of new-onset atrial fibrillation (AF) or atrial flutter (AFL) and their influence on clinical outcomes. Background: Limited information is available on whether atrial fibrillation incidence is affected differentially by different classes of antihypertensive medications or treatment with statins. Methods: AF/AFL was identified from baseline and follow-up electrocardiograms performed biannually. Analyses were performed to identify characteristics associated with baseline AF/AFL and its subsequent incidence. Results: AF/AFL was present at baseline in 423 participants (1.1%), more frequent in men (odds ratio: 1.72; 95% confidence interval [CI]: 1.37 to 2.17) and nonblacks (odds ratio: 2.09; 95% CI: 1.58 to 2.75). Its prevalence increased with age (p < 0.001) and was associated with CHD, cardiovascular disease, obesity, and high-density lipoprotein cholesterol <35 mg/dl. New-onset AF/AFL was associated with the same baseline risk factors plus electrocardiogram left ventricular hypertrophy. It occurred in 641 participants (2.0%) and, excluding doxazosin, did not differ by antihypertensive treatment group or, in a subset of participants, by pravastatin versus usual care. Baseline AF/AFL was associated with increased mortality (hazard ratio [HR]: 2.82; 95% CI: 2.36 to 3.37; p < 0.001), stroke (HR: 3.63; 95% CI: 2.72 to 4.86; p < 0.001), heart failure (HR: 3.17; 95% CI: 2.38 to 4.25; p < 0.001), and fatal CHD or nonfatal myocardial infarction (HR: 1.64; 95% CI: 1.22 to 2.21; p < 0.01). There was a nearly 2.5-fold increase in mortality risk when AF/AFL was present at baseline or developed during the trial (HR: 2.42; 95% CI: 2.11 to 2.77; p < 0.001). Conclusions: In this high-risk hypertensive population, pre-existing and new-onset AF/AFL were associated with increased mortality. Excluding doxazosin, treatment assignment to either antihypertensive drugs or pravastatin versus usual care did not affect AF/AFL incidence. (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]; NCT00000542) [Copyright &y& Elsevier]

Objectives: This study sought to assess the pharmacokinetics and clinical effects of oral BG9928 in heart failure (HF) patients. Background: Declining renal function during HF treatment is associated with poor outcomes. BG9928, a selective inhibitor of the A1 adenosine receptor, is proposed to cause natriuresis without causing a decline in renal function. Methods: A randomized, double-blind, placebo-controlled study was conducted in patients with HF and systolic dysfunction who were receiving standard therapy. Patients were randomized to receive BG9928 (3, 15, 75, or 225 mg) or placebo orally for 10 days. The primary end point was change in sodium excretion. Changes in potassium excretion, creatinine clearance, and body weight also were evaluated. Results: A total of 50 patients were studied. BG9928 increased sodium excretion compared with placebo, and natriuresis was maintained over 10 days with little kaliuresis. A linear trend in dose response was observed on day 1 (p = 0.04) but not on days 6 or 10. Adjusted creatinine clearance was unchanged over the 10 days. Patients who received 15, 75, or 225 mg of BG9928 had a reduction in body weight compared with placebo (−0.6, −0.7, −0.5, vs. +0.3 kg, respectively) at the end of study. BG9928 was well tolerated. The pharmacokinetic profile of BG9928 was consistent with once-daily dosing. Conclusions: Oral BG9928 over the dose range of 3 to 225 mg/day produced significant increases in sodium excretion in patients with stable HF without causing kaliuresis or reducing renal function. [Copyright &y& Elsevier]

Objectives: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). Background: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. Methods: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. Results: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. Conclusions: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation. [Copyright &y& Elsevier]

: ObjectivesThe goal of this study was to determine the prevalence of worsening renal function (WRF) among hospitalized heart failure (HF) patients, clinical predictors of WRF, and hospital outcomes associated with WRF.: BackgroundImpaired renal function is associated with poor outcomes among chronic HF patients.: MethodsChart reviews were performed on 1,004 consecutive patients admitted for a primary diagnosis of HF from 11 geographically diverse hospitals. Cox regression model analysis was used to identify independent predictors for WRF, defined as a rise in serum creatinine of >0.3 mg/dl (26.5 μmol/l). Bivariate analysis was used to determine associations of development of WRF with outcomes (in-hospital death, in-hospital complications, and length of stay).: ResultsAmong 1,004 HF patients studied, WRF developed in 27%. In the majority of cases, WRF occurred within three days of admission. History of HF or diabetes mellitus, admission creatinine ≥1.5 mg/dl (132.6 μmol/l), and systolic blood pressure >160 mm Hg were independently associated with higher risk of WRF. A point score based on these characteristics and their relative risk ratios predicted those at risk for WRF. Hospital deaths (adjusted risk ratio [ARR] 7.5; 95% confidence intervals [CI] 2.9, 19.3), complications (ARR 2.1; CI 1.5, 3.0), and length of hospitalizations >10 days (ARR 3.2, CI 2.2, 4.9) were greater among patients with WRF.: ConclusionsWorsening renal function occurs frequently among hospitalized HF patients and is associated with significantly worse outcomes. Clinical characteristics available at hospital admission can be used to identify patients at increased risk for developing WRF. [Copyright &y& Elsevier]

Objectives: This study examined the outcomes of new-onset heart failure (HF) outpatients managed by cardiologists and primary care (PC) physicians.Background: Several studies have sought differences in outcomes between patients with HF managed by cardiologists and PC physicians, but most focused on inpatients, who often represent later stages of HF, whereas many treatments have their impact by delaying disease progression.Methods: This was a retrospective cohort study of incident HF identified between 1996 and 1997 in a staff model health maintenance organization. Cardiology care was defined as >/=2 visits or >/=25% of total medical outpatient visits to cardiology. Records from a cohort of 403 patients with new-onset outpatient HF were reviewed. The main outcome measure was a combination of death and/or cardiovascular hospitalization at 24 months.Results: Cardiologists' patients (n = 198) were younger (66 vs. 71 years, p = 0.001), were more likely men (54% vs. 46%, p = 0.01), had coronary artery disease (64% vs. 42%, p = 0.001), and had a low (Conclusions: Cardiology care at this early stage of HF is associated with improved guideline adherence and a reduced risk of the composite outcome of death plus cardiovascular hospitalization. [ABSTRACT FROM AUTHOR]

: ObjectivesThis study examined the outcomes of new-onset heart failure (HF) outpatients managed by cardiologists and primary care (PC) physicians.: BackgroundSeveral studies have sought differences in outcomes between patients with HF managed by cardiologists and PC physicians, but most focused on inpatients, who often represent later stages of HF, whereas many treatments have their impact by delaying disease progression.: MethodsThis was a retrospective cohort study of incident HF identified between 1996 and 1997 in a staff model health maintenance organization. Cardiology care was defined as ≥2 visits or ≥25% of total medical outpatient visits to cardiology. Records from a cohort of 403 patients with new-onset outpatient HF were reviewed. The main outcome measure was a combination of death and/or cardiovascular hospitalization at 24 months.: ResultsCardiologists’ patients (n = 198) were younger (66 vs. 71 years, p = 0.001), were more likely men (54% vs. 46%, p = 0.01), had coronary artery disease (64% vs. 42%, p = 0.001), and had a low (≤45%) ejection fraction (EF) (66% vs. 44%, p < 0.001) compared with PC physicians’ patients. More cardiologists’ patients received an EF assessment (94% vs. 74%, p < 0.001), angiotensin-converting enzyme inhibitors (83% vs. 68%, p < 0.001), and beta-blockers (38% vs. 22%, p < 0.001). In multivariate proportional hazards modeling that included variables that differed between providers and univariate predictors of outcomes, cardiology care was an independent predictor of a lower risk for the combined outcome (hazard ratio 0.62, confidence interval 0.42 to 0.93, p = 0.02).: ConclusionsCardiology care at this early stage of HF is associated with improved guideline adherence and a reduced risk of the composite outcome of death plus cardiovascular hospitalization. [Copyright &y& Elsevier]