Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Racial differences in blood pressure response to angiotensin-converting enzyme inhibitors in children: a meta-analysis.

Angiotensin-converting enzyme (ACE) inhibitors are frequently used to treat hypertension in children.(1) ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and cardiac hypertrophic properties of angiotensin II and the vasodilatory and natriuretic properties of bradykinin; they also alter the metabolism of other vasoactive substances.(2) Through these mechanisms, ACE inhibitors decrease systemic vascular resistance and promote natriuresis without increasing heart rate. This study evaluated the results of six trials of ACE inhibitors in children, using meta-analytic techniques to estimate the effect of race on blood pressure response.

Association of intradialytic blood pressure changes with hospitalization and mortality rates in prevalent ESRD patients.

The relationship between blood pressure (BP) and clinical outcomes among hemodialysis patients is complex and incompletely understood. This study sought to assess the relationship between blood pressure changes with hemodialysis and clinical outcomes during a 6-month period. This study is a secondary analysis of the Crit-Line Intradialytic Monitoring Benefit Study, a randomized trial of 443 hemodialysis subjects, designed to determine whether blood volume monitoring reduced hospitalization. Logistic regression was used to estimate the association between BP changes with hemodialysis (Deltasystolic blood pressure=postdialysis-predialysis systoic BP (SBP) and the primary outcome of non-access-related hospitalization and death. Subjects whose systolic blood pressure fell with dialysis were younger, took fewer blood pressure medications, had higher serum creatinine, and higher dry weights. After controlling for baseline characteristics, lab variables, and treatment group, subjects whose SBP remained unchanged with hemodialysis (N=150, DeltaSBP -10 to 10 mm Hg) or whose SBP rose with hemodialysis (N=58, DeltaSBP > or =10 mm Hg) had a higher odds of hospitalization or death compared to subjects whose SBP fell with hemodialysis (N=230, DeltaSBP < or =-10 mm Hg) (odds ratio: 1.85, confidence interval: 1.15-2.98; and odds ratio: 2.17, confidence interval: 1.13-4.15). Subjects whose systolic blood pressure fell with hemodialysis had a significantly decreased risk of hospitalization or death at 6 months, suggesting that hemodynamic responses to dialysis are associated with short-term outcomes among a group of prevalent hemodialysis subjects. Further research should attempt to elucidate the mechanisms behind these findings.

No benefit from pulmonary artery catheters for critically ill patients

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Initial experience with factor-Xa inhibition in percutaneous coronary intervention: the XaNADU-PCI Pilot.

BACKGROUND: Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). OBJECTIVES: To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. PATIENTS AND METHODS: Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I-III were designed to achieve concentrations of > 100 ng mL-1, > 75 ng mL-1, and > 150 ng mL-1. Stage IV used the stage III regimen but included patients recently given heparin. RESULTS: At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL-1 in stages I-IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL-1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose. CONCLUSIONS: Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study.

Time-based risk assessment after myocardial infarction. Implications for timing of discharge and applications to medical decision-making.

AIMS: We evaluated timing of adverse cardiac events after thrombolysis to guide length of stay after ST-segment elevation myocardial infarction. METHODS AND RESULTS: Kaplan-Meier survival curves described timing of major postinfarction complications in 41021 fibrinolytic-treated patients in GUSTO-I. Using model-fitting, these data were best explained by a mixed-exponential survival model: an acute curve describing most adverse events and a chronic curve describing a lower background rate. We replicated this strategy in 15059 fibrinolytic-treated patients in GUSTO-III. From the relation between time and events described by the model's acute curve in GUSTO-III, we proposed times for hospital discharge. The acute curve explained 97% of deaths and 68%-96% of various event composites. Of complications within 10 days, 90% of deaths and 70% of acute curve death, stroke, shock, heart failure, or reinfarction occurred by 24 h. By 2.7 days, 95% of deaths, stroke, shock, heart failure, or reinfarction occurred. Most major ventricular arrhythmias occurred within 24 h, after which the hazard curve was flat. CONCLUSIONS: Mixed-exponential survival modelling describes timing of post-infarction complications and supports discharge 4 days after uncomplicated infarction. Such time-based risk assessment could guide decision-making in other settings in which randomized studies are impractical.

A randomized, placebo-controlled trial of enoxaparin after high-risk coronary stenting: the ATLAST trial.

OBJECTIVES: We performed a multicenter, double-blind placebo-controlled trial to examine the efficacy and safety of enoxaparin in patients at high risk for stent thrombosis (ST). BACKGROUND: The optimal antithrombotic regimen for such patients is unknown. METHODS: We randomized 1,102 patients with clinical, angiographic or ultrasonographic features associated with an increased risk of ST to receive either twice-daily injections of weight-adjusted enoxaparin or placebo for 14 days after stenting. All patients received aspirin and ticlopidine. The primary end point was a 30-day composite end point of death, myocardial infarction (MI) or urgent revascularization. RESULTS: The target enrollment for the study was 2,000 patients. However, the trial was terminated prematurely at 1,102 patients after interim analysis revealed an unexpectedly low event rate. The primary outcome occurred in 1.8% enoxaparin-treated patients versus 2.7% treated with placebo (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.29 to 1.5, p = 0.30); for death or MI the rates were 0.9% vs. 2.2%, respectively (OR 0.41, 95% CI 0.14 to 1.2, p =0.13); and for MI, 0.4% vs. 1.6%, respectively (OR 0.22, 95% CI 0.05 to 0.99, p = 0.04). The groups had comparable rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p =0.08), but minor nuisance bleeding was increased with enoxaparin (25% vs. 5.1%, p < 0.001). CONCLUSIONS: The clinical outcomes of patients at increased risk of ST are more favorable than previously reported, rendering routine oral antiplatelet therapy adequate for most. However, given its relative safety and potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients.

Prognostic usefulness of the six-minute walk in patients with advanced congestive heart failure secondary to ischemic or nonischemic cardiomyopathy.

Clinicians have relied on history and results from physical examinations to guide treatment of patients with advanced congestive heart failure, but these results may not reflect disease severity or hemodynamic status. We assessed how the distance walked in 6 minutes relates to clinical outcomes and symptoms of such patients. We compared the rates of death, hospitalization, and their composite at 1 year by the distance walked in 6 minutes at baseline and at 1 month, and by the change in distance between baseline and 1 month in 440 patients enrolled in a randomized trial. We also assessed the relations of baseline distance walked to symptom score and New York Heart Association class. The median distance increased from 218 m at baseline to 280 m at 1 month. Of 365 patients able to perform the baseline walk, 121 (33%) died and 217 (60%) were hospitalized compared with 46 (61%) and 34 (45%) of 75 patients unable to walk at baseline. Baseline distance significantly predicted mortality (hazard ratio 0.58/100-m increase, 95% confidence interval 0.50 to 0.68, p <0.001), even after adjustment. Baseline distance also significantly predicted hospitalization and the composite end point, as did the 1-month distance walked. The change in distance walked from baseline to 1 month did not predict any end point. Baseline distance correlated only moderately with symptom score (r = -0.385, p <0.001) and New York Heart Association class (r = -0.468, p <0.001). Distance walked during 6 minutes independently and strongly predicts mortality and hospitalization in patients with advanced congestive heart failure. This may be a simple, noninvasive, objective way to risk-stratify these patients and standardize their treatment.

Relationship between transferrin saturation and iron stores in the African American and US Caucasian populations: analysis of data from the third National Health and Nutrition Examination Survey.

In previous analyses of transferrin saturation data in African Americans and Caucasians from the second National Health and Nutrition Examination Survey (NHANES II), subpopulations were found consistent with population genetics for common loci that influence iron metabolism. The goal of this new study was to determine if these transferrin saturation subpopulations have different levels of iron stores. Statistical mixture modeling was applied to transferrin saturation data for African Americans and Caucasians from the third National Health and Nutrition Examination Survey (NHANES III), and then the mean serum ferritin concentrations were determined for the transferrin saturation subpopulations that were identified. After adjustment for diurnal variation, 3 subpopulations of transferrin saturation were identified in each racial group. Satisfying Hardy-Weinberg conditions for major locus effects, in both racial groups the sum of the square roots of the proportion with the lowest mean transferrin saturation and the proportion with the highest mean transferrin saturation was approximately 1. When weighted to reflect the US adult population as a whole, these subpopulations of increasing transferrin saturations had progressively increasing mean age-adjusted serum ferritin concentration values in each ethnic grouping as stratified by sex (trend test, P <.002 for all). These results are consistent with the concept that population transferrin saturation subpopulations reflect different levels of storage iron.

Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials.

Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

Assessing the clinical and economic burden of coronary artery disease: 1986-1998.

BACKGROUND: The acute phase of coronary artery disease (CAD) is dramatic and receives much attention because of its high mortality and associated treatment cost. However, the acute phase typically resolves within 30 days whereas CAD is a chronic disease, which most patients will live with for more than a decade. We compared the clinical and economic burden of CAD during the acute phase (first 30 days) with that in the postacute phase (31st day through 10 years). METHODS: We included acute coronary syndrome (ACS) patients with significant CAD receiving an initial cardiac catheterization at Duke University Medical Center between 1986 and 1997 with follow-up continuing through 1998. Inpatient medical costs were estimated from ACS clinical trial and economic study data. Costs were adjusted to 1997 values and discounted at 3% per annum. RESULTS: Our study included 9,876 ACS patients (5,557 with an acute myocardial infarction [MI] and 4,319 with unstable angina [UA]). Acute MI patients had higher 30-day mortality than UA patients (5.6% vs. 2.3%, P <0.001). In addition, acute MI and UA patients had significant 10-year unadjusted and adjusted survival differences (both P <0.001). For patients who survived to 30 days, there was no difference in 10-year survival between acute MI and UA patients before adjustment (P = 0.472). After adjustment, however, unstable angina patients who survived to 30 days had greater survival than myocardial infarction patients (P = 0.011). Mean 10-year discounted ACS inpatient medical costs were $45,253 ($23,510 acute phase and $21,819 postacute phase, P = 0.002). Ten year costs for unstable angina patients were $46,423 ($21,824 acute phase and $24,599 postacute phase, P = 0.003); ten year costs for myocardial infarction patients were $44,663 ($24,823 acute phase and $19,840 postacute phase, P <0.001). CONCLUSIONS: We found that the clinical and economic burden of CAD continues long after a patient's acute event has resolved and that postacute CAD cardiac event rates and inpatient medical costs may be higher than previously estimated. With much of all medical costs occurring in the postacute phase, the potential for effective secondary prevention therapies is substantial.

Hemodynamic profiles of advanced heart failure: association with clinical characteristics and long-term outcomes.

BACKGROUND: Classifying patients with advanced congestive heart failure (CHF) by baseline measures of congestion and perfusion has been used to estimate hemodynamic status and to select and titrate therapy. We describe clinical characteristics of 4 hemodynamic profiles-wet/cold, wet/warm, dry/cold, and dry/warm-in patients with advanced CHF and assess relations between symptoms, physical signs, and outcomes with each profile. METHODS AND RESULTS: We retrospectively assessed baseline symptoms, physical-examination variables, and 1-year outcomes of 440 patients in a randomized trial. With univariable and multivariable logistic regression, we examined relations of physical-examination variables to hemodynamic profiles. We also assessed the rates of death and death or readmission by profile. Severity of CHF symptoms did not predict the wet-versus-dry profile or cold-versus-warm status, despite significant differences in hemodynamics among groups. Of the physical-examination variables, only a lower proportional pulse pressure was a significant multivariable predictor of the wet category. Among wet patients (n = 348), this same variable was the only significant multivariable predictor of the cold category. For dry patients (n = 92), the cold category was predicted in multivariable analysis by supine heart rate and hepatomegaly. Survival was similar among profiles: wet/cold, 54.2% (n = 91); wet/warm, 58.3% (n = 105); dry/cold, 78.9% (n = 15); and dry/warm, 67.1%, P =.13 (n = 49). Event-free survival also was similar among profiles: wet/cold, 22.0% (n = 37); wet/warm, 29.4% (n = 53); dry/cold, 42.1% (n = 8); and dry/warm, 31.5%, P =.44 (n = 23). CONCLUSIONS: The patient's history and physical examination alone may lead to inaccurate estimation of hemodynamic status and thus suboptimal management for patients with advanced CHF.

Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin t-positive status: the paragon-B troponin T substudy.

BACKGROUND: Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. METHODS AND RESULTS: We prospectively studied 1160 patients with non-ST-segment elevation ACS randomized in PARAGON-B to receive lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (>/=0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P=0.01) among TnT-positive patients but not among TnT-negative patients (11.2% for placebo versus 10.8% for lamifiban, P=0.86; P=0.08 for test of interaction between TnT status and treatment assignment). This pattern held for the end points of death alone and death or myocardial (re)infarction at 30 days. Peak TnT level at 48 hours did not differ with lamifiban treatment. CONCLUSIONS: TnT predicts poor short-term outcomes in non-ST-segment elevation ACS. Treatment benefit with lamifiban is limited almost exclusively to TnT-positive patients, reducing 30-day adverse outcomes to a rate nearly identical to that of negative patients.

Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: the ESPRIT trial: a randomized controlled trial.

CONTEXT: The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial showed the efficacy of adjunctive, double-bolus eptifibatide therapy in reducing ischemic complications of nonurgent coronary stent implantation at 48 hours and at 30 days. OBJECTIVE: To determine whether the beneficial effects of eptifibatide persist at 6 months after treatment. DESIGN: Follow-up study of a randomized, double-blind, placebo-controlled, crossover-permitted trial conducted from June 1999 through February 2000. SETTING: Ninety-two tertiary care centers in the United States and Canada. PARTICIPANTS: A total of 2064 patients scheduled to undergo nonurgent percutaneous coronary intervention with stent implantation. INTERVENTION: Patients were randomly assigned to receive placebo or eptifibatide (two 180-microg/kg boluses 10 minutes apart and continuous infusion of 2.0 microg/kg per minute), started immediately before stent implantation and continued for 18 to 24 hours. Complete follow-up data were available for 988 (95.0%) of 1040 patients given eptifibatide and 977 (95.4%) of 1024 patients given placebo. MAIN OUTCOME MEASURES: Composite rates of death or myocardial infarction (MI); death, MI, or target vessel revascularization; and their individual components 6 months after enrollment, compared between the 2 groups. RESULTS: By 6 months, the composite end point of death or MI had occurred in 7.5% of eptifibatide-treated patients and in 11.5% of placebo-treated patients (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.47-0.84; P =.002). The composite of death, MI, or target vessel revascularization was 14.2% in eptifibatide-treated patients vs 18.3% in placebo-treated patients (HR, 0.75; 95% CI, 0.60-0.93; P =.008). Most of this benefit accrued early (<48 hours after initiation of therapy) and was maintained through 6 months. Six-month mortality in the eptifibatide group was 0.8% vs 1.4% in the placebo group (HR, 0.56; 95% CI, 0.24-1.34; P =.19) and target vessel revascularization occurred in 8.6% of the eptifibatide group vs 9.4% of the placebo group (HR, 0.91; 95% CI, 0.68-1.22; P =.51). CONCLUSION: Adjunctive eptifibatide therapy during coronary stent implantation provides benefit through 6-month follow-up.

Reactivation of ischemic events in acute coronary syndromes: results from GUSTO-IIb. Gobal Use of Strategies To Open occluded arteries in acute coronary syndromes.

OBJECTIVES: We sought to determine the incidence of and risk factors for thrombotic events early after discontinuing antithrombin therapy in patients with acute coronary syndromes. BACKGROUND: Discontinuation of treatment with heparin and other thrombin inhibitors in patients with unstable coronary syndromes has related to clinical and biochemical evidence of early reactivation of thrombosis. METHODS: We studied 8,943 of the 12,142 patients with acute coronary syndromes enrolled in the Global Use of Strategies To Open occluded arteries in acute coronary syndromes trial of hirudin versus heparin. We excluded patients who received no study drug, lacked timing data, died or had myocardial (re)infarction [(re)MI] during study-drug infusion, or began heparin treatment within 2 h after treatment with the study drug was stopped. We assessed the incidence and timing of (re)MI by type and timing of antithrombin treatment. RESULTS: In all, 215 patients (2.4%) suffered (re)MI, 49 within 12 h of antithrombin therapy discontinuation and 166 between hour 12 and hospital discharge. The duration of infusion did not differ between the hirudin and heparin groups. The rate of early re(MI) after drug therapy discontinuation was significantly higher in patients given heparin versus hirudin (0.8% vs. 0.3%, p = 0.002). Patients with (re)MI had higher mortality at 30 days (23.6% vs. 2.4%, p = 0.001) and 1 year (35.2% vs. 6.7%, p = 0.001) compared with patients without (re)MI. CONCLUSIONS: The incidence of (re)MI was clustered within 12 h of heparin therapy discontinuation, with the greatest risk within 4 h. There was no evidence of early reactivation of thrombotic events after hirudin. Patients who had (re)infarction had worse outcomes. Better understanding of the mechanism and possible prevention of recurrent thrombosis is needed.

Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE): design and rationale.

BACKGROUND: There is little information about how to adjust pharmacologic agents in the treatment of patients with advanced congestive heart failure (CHF). Some studies have suggested that use of pulmonary artery catheterization to guide reductions in filling pressures may improve outcomes for patients with heart failure who are hospitalized with evidence of elevated filling pressures. However, there is no consensus regarding the true utility of this strategy. A randomized clinical trial is needed to test the safety, efficacy, and treatment benefit of pulmonary artery catheterization in patients with advanced CHF. STUDY DESIGN: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial is a multicenter, randomized trial designed to test the long-term safety and efficacy of treatment guided by hemodynamic monitoring and clinical assessment versus that guided by clinical assessment alone in patients hospitalized with New York Heart Association class IV CHF. Five hundred patients will be randomly assigned to receive either medical therapy guided by a combination of clinical assessment and hemodynamic monitoring (PAC arm) or medical therapy guided by clinical assessment alone (CLIN arm). The primary end point of ESCAPE will be the number of days that patients are hospitalized or die during the 6-month period after randomization. Secondary end points will include changes in mitral regurgitation, peak oxygen consumption, and natriuretic peptide levels. Other secondary end points will be pulmonary artery catheter-associated complications, resource utilization, quality of life measures, and patient preferences regarding survival. IMPLICATIONS: The primary goal of ESCAPE will be to provide information about the utility of the pulmonary artery catheter in patients with advanced heart failure, independent of various treatment approaches used by individual physicians. In addition, this study will define current outcomes for this severely compromised population.