Context Pulmonary artery catheters (PACs) have been used to guide therapy in
multiple settings, but recent studies have raised concerns that PACs may lead
to increased mortality in hospitalized patients.
Objective To determine whether PAC use is safe and improves clinical outcomes
in patients hospitalized with severe symptomatic and recurrent heart failure.
Design, Setting, and Participants The Evaluation Study of Congestive Heart Failure and Pulmonary Artery
Catheterization Effectiveness (ESCAPE) was a randomized controlled trial of
433 patients at 26 sites conducted from January 18, 2000, to November 17,
2003. Patients were assigned to receive therapy guided by clinical assessment
and a PAC or clinical assessment alone. The target in both groups was resolution
of clinical congestion, with additional PAC targets of a pulmonary capillary
wedge pressure of 15 mm Hg and a right atrial pressure of 8 mm Hg. Medications
were not specified, but inotrope use was explicitly discouraged.
Main Outcome Measures The primary end point was days alive out of the hospital during the
first 6 months, with secondary end points of exercise, quality of life, biochemical,
and echocardiographic changes.
Results Severity of illness was reflected by the following values: average left
ventricular ejection fraction, 19%; systolic blood pressure, 106 mm Hg; sodium
level, 137 mEq/L; urea nitrogen, 35 mg/dL (12.40 mmol/L); and creatinine,
1.5 mg/dL (132.6 μmol/L). Therapy in both groups led to substantial reduction
in symptoms, jugular venous pressure, and edema. Use of the PAC did not significantly
affect the primary end point of days alive and out of the hospital during
the first 6 months (133 days vs 135 days; hazard ratio [HR], 1.00 [95% confidence
interval {CI}, 0.82-1.21]; P = .99), mortality
(43 patients [10%] vs 38 patients [9%]; odds ratio [OR], 1.26 [95% CI, 0.78-2.03]; P = .35), or the number of days hospitalized
(8.7 vs 8.3; HR, 1.04 [95% CI, 0.86-1.27]; P = .67).
In-hospital adverse events were more common among patients in the PAC group
(47 [21.9%] vs 25 [11.5%]; P = .04). There
were no deaths related to PAC use, and no difference for in-hospital plus
30-day mortality (10 [4.7%] vs 11 [5.0%]; OR, 0.97 [95% CI, 0.38-2.22]; P = .97). Exercise and quality of life end points
improved in both groups with a trend toward greater improvement with the PAC,
which reached significance for the time trade-off at all time points after
randomization.
Conclusions Therapy to reduce volume overload during hospitalization for heart failure
led to marked improvement in signs and symptoms of elevated filling pressures
with or without the PAC. Addition of the PAC to careful clinical assessment
increased anticipated adverse events, but did not affect overall mortality
and hospitalization. Future trials should test noninvasive assessments with
specific treatment strategies that could be used to better tailor therapy
for both survival time and survival quality as valued by patients.
Advances in medical therapy have improved outcomes for many ambulatory
patients with heart failure and low ejection fraction (EF).1-4 However,
each year an estimated 250 000 to 300 000 patients are hospitalized
for heart failure with low EF,5 and the 1-year
survival rate after hospitalization may be as low as 50%, even with recommended
medical therapies.6,7
In nonrandomized studies, patients undergoing therapy with vasodilators
and diuretics to reduce filling pressures to near normal levels have had acute
and sustained improvements in hemodynamics, mitral regurgitation, and exercise
tolerance.8-15 Without
a randomized study of hemodynamic monitoring with the pulmonary artery catheter
(PAC), however, it could not be determined whether PACs improved outcomes
in addition to other components of intensive heart failure management.
There is considerable controversy over use of the PAC in critical illness.
The Study to Understand Prognoses and Preferences for Outcomes and Risks of
Treatments (SUPPORT) trial demonstrated higher mortality for patients thought
to require PAC during hospitalization, although without excess risk for patients
with heart failure.16 Reports from acute myocardial
infarction populations further raised concerns that PACs increased mortality,
and a moratorium on PAC use was proposed.17 Recommendations
from a working group of representatives from the National Heart, Lung, and
Blood Institute (NHLBI), the Food and Drug Administration, and academic experts
in cardiology, pulmonology, surgery, nursing, and critical care led to a trial
designed to test the PAC in patients with chronic heart failure.18
The complexity of this population and the challenge of hemodynamic measurement
made experience in hemodynamic studies desirable. However, refinement of clinical
assessment based on prior hemodynamic investigation could diminish the impact
of PAC information. Recognizing this conflict,18 the
decision was made to test the PAC with experienced heart failure investigators.
For the Evaluation Study of Congestive Heart Failure and Pulmonary Artery
Catheterization Effectiveness (ESCAPE), the primary hypothesis was that for
patients with severe heart failure, therapy guided by PAC monitoring and clinical
assessment would lead to more days alive and fewer days hospitalized during
6 months compared with therapy guided by clinical assessment alone.
ESCAPE was an NHLBI-sponsored randomized trial conducted at 26 experienced
heart failure centers in the United States and Canada. The Brigham and Women’s
Hospital served as the clinical coordinating center, and Duke Clinical Research
Institute was the data coordinating center and performed all statistical analyses.
The NHLBI appointed an independent data and safety monitoring board. Participating
institutional review boards approved the protocol, and written informed consent
was obtained from all patients.
Inclusion criteria were designed to select patients with severe symptomatic
heart failure despite recommended therapies.18 The
target patient was sufficiently ill with advanced heart failure to make use
of the PAC reasonable, but also sufficiently stable to make crossover to PAC
for urgent management unlikely. Severity prior to admission could be met by
the following criteria: (1) hospitalization for heart failure within the past
year; (2) urgent visit to the emergency department; or (3) treatment during
the preceding month with more than 160 mg of furosemide daily (or equivalent).
Randomization required at least 3 months of symptoms despite angiotensin-converting
enzyme (ACE) inhibitors and diuretics, left ventricular (LV) EF 30% or less,
systolic blood pressure 125 mm Hg or less, and at least 1 sign and 1 symptom
of congestion. Exclusion criteria to minimize confounding comorbidities or
urgent crossover included creatinine level greater than 3.5 mg/dL (309.4 μmol/L),
or prior use of dobutamine or dopamine more than 3 μg/kg/min, or any prior
use of milrinone during the current hospitalization. Right heart catheterization
to assess pulmonary hypertension during transplant evaluation was permitted
in patients receiving therapy guided by clinical assessment alone if performed
at the end of hospitalization.
A concurrent PAC registry was established to characterize hospitalized
patients receiving PACs considered to be required during heart failure management.
Study Design and Analyses
Patients were randomly assigned 1:1 to therapy guided by clinical assessment
only (clinical assessment group) or therapy guided by clinical assessment
and the PAC (PAC group). Randomization was stratified by site using random
block sizes of 2 or 4 through a central telephone center. The treatment goal
in the clinical assessment group was resolution of clinical signs and symptoms
of congestion, particularly jugular venous pressure elevation, edema, and
orthopnea. Treatment goals in the PAC group were the same, with the addition
of pulmonary capillary wedge pressure (PCWP) of 15 mm Hg and right atrial
pressure of 8 mm Hg. Therapy was adjusted in both groups to avoid progressive
renal dysfunction or symptomatic systemic hypotension.
The protocol did not specify drug selection or dosing. Investigators
were encouraged to follow national guidelines for treatment of heart failure
and to primarily use intravenous diuretics and vasodilators. The use of inotropic
agents for routine management was consistently and explicitly discouraged.
No specific instructions were given regarding nesiritide, which became available
during the course of the trial.
The Pulmonary Artery Catheter Education Project, a computer-based program
created by the NHLBI, the Food and Drug Administration, and the American College
of Physicians, was used at study initiation to train investigators and coordinators
(http://www.pacep.org/asahq). Catheters were selected according
to individual institutional practice. In the PAC group, hemodynamics were
measured twice at baseline and at least twice daily thereafter, with pressure
measurement from paper readings. A specific case report form listed anticipated
PAC complications.
Patients were seen at 7 to 14 days, and 1, 2, 3, and 6 months after
discharge. Data were collected on clinical status, medications, exercise,
and quality of life measurements. Race and ethnicity were assessed by the
study coordinator from patients and chart information to determine degree
of diverse representation in the study population. The primary end point,
days alive out of the hospital during 6 months following randomization, was
analyzed using the Cox proportional hazards model. Component end points included
time to events. End points were calculated with patients receiving transplant
or assist devices coded as dead, then recalculated coded as alive.
Because patients and physicians were not blinded to treatment, physiologic
secondary end points, focusing on mitral regurgitation (the subject of pending
analysis), natriuretic peptides, and peak oxygen consumption, were selected
as measurable without knowledge of group assignment. Other functional end
points were 6-minute walk distance,19 the Minnesota
Living with Heart Failure questionnaire,20 and
the time trade-off tool,21 which quantifies
how many months of life out of 24 months patients would trade to feel better,
through a series of binary questions asked by a trained coordinator, as has
been described for moderate-severe heart failure. All baseline functional
measures were made before randomization. A new end point of time trade-off–adjusted
survival was prospectively defined for exploratory analysis as the integrated
product of the days alive and the proportion of months preferred in current
health at each time point.
The original design included 500 randomized patients, based on the assumption
that the control group would have an expected 40 days dead or hospitalized
with an SD of 30. The treated group was assumed to have an expected number
of days of 32 (0.8 × 40). This resulted in an estimated power
of 84%, assuming normality of days hospitalized (assuming a 2-sided test at
an α level of .05). Interim unblinded analyses for efficacy occurred
after 19%, 46%, 59%, and 67% of the patients had been enrolled. Approximate
O’Brien-Fleming boundaries were used based on the group-sequential methods
of Lan et al.22 No provision was made for stopping
early for futility. None of the tests were close to the stopping boundaries.
The secondary end points, including exercise, natriuretic peptides,
and quality of life, were analyzed with the t test
using SAS version 8.2 (SAS Institute Inc, Cary, NC) with an α level
of .05. All analyses were based on intention to treat.
From January 18, 2000, to November 17, 2003, 433 patients were enrolled
(Figure 1). The data and safety monitoring
board recommended that the NHLBI stop the trial before enrolling 500 patients
due to concerns of early adverse events and the unlikelihood of achieving
a significant difference in the primary end point.
The 2 randomized groups had similar baseline characteristics (Table 1), with 391 (90%) taking ACE inhibitors
or angiotensin-receptor blockers, 268 (62%) taking β-blockers, and 31
(7%) with implantable defibrillators. During the same time, patients receiving
the PAC without randomization (PAC registry) had higher LVEF, but more compromise
of blood pressure, serum sodium and creatinine levels, and inotropic therapy
(35% vs 15%).
Treatment After Randomization
Intravenous diuretics were used in all patients. Vasodilator therapy
was used in 80 (37%) patients in the PAC group and 42 patients (19%) in the
clinical assessment group (total nesiritide, 66 [15%]; nitroprusside, 50 [12%];
nitroglycerin, 16 [4%]). Inotropic therapy was used in 94 (44%) patients in
the PAC group and 86 patients (39%) in the clinical assessment group. Discharge
prescriptions included ACE inhibitors/angiotensin-receptor blockers for 196
(91%) patients in the PAC group and 195 patients (89%) in the clinical assessment
group, and β-blockers for 140 (65%) patients in the PAC group and 128
patients (59%) in the clinical assessment group.
PACs were placed for adjustment of therapy in 198 (92%) patients in
the PAC group and 21 patients (10%) in the clinical assessment group during
hospitalization. PACs in patients in the treatment group were in place for
a median of 1.9 days, during which all hemodynamic parameters improved (Table 2). Substantial impact of therapy on clinical
goals by the time of discharge was similar in both groups (Table 3). Although average weight loss was 3.2 kg for patients in
the clinical assessment group vs 4.0 kg for patients in the PAC group, serum
creatinine level worsened less often in the PAC group.
Use of the PAC did not affect the primary end point of days alive out
of the hospital (Figure 2). The overall
neutrality of the intervention was consistent across demographic subgroups
(Figure 3). There were no significant
differences in time to death or hospitalization, deaths, or days hospitalized
(Table 4). Both groups had a median
of 2.0 hospitalizations per patient. Coding the 36 patients who underwent
cardiac transplantation or LV assist device placement as either dead or alive
did not change the results.
There were no clinical subgroups in which benefit or harm was shown.
There was a trend for better PAC outcomes in the centers with higher volume
enrollment. There was no evidence of benefit or harm from the PAC in relation
to intravenous vasoactive therapy (Table 5).
Adverse events specifically attributed to PACs occurred in 9 patients
in the PAC group and 1 patient in the clinical assessment group later receiving
a PAC (Table 6). These specific events
were PAC-related infection (4 patients), bleeding (2 patients), catheter knotting
(2 patients), pulmonary infarction/hemorrhage (2 patients), and ventricular
tachycardia (1 patient). There were no hospital deaths attributed to the PAC.
Adverse events, most commonly infection, occurred in-hospital almost twice
as often in the PAC patients, but occurred in 143 patients in each group over
6 months. Other cardiac procedures occurred in 81 (38%) patients in the PAC
group and 89 (41%) in the clinical assessment group during hospitalization.
Natriuretic peptides decreased similarly in both groups. Functional
end points improved significantly during hospitalization in both groups, with
a trend for more improvement in the PAC group (Figure 4). The Minnesota Living with Heart Failure questionnaire
improved in both groups by 1 month, with greater improvement in the PAC group.
By 6 months, scores in the clinical assessment group had improved to match
the PAC group.
The time trade-off showed greater improvement for the PAC group compared
with the clinical assessment group at all time points (1, 2, 3, and 6 months; P = .001-.02). By the end of the study, the average
improvement (decrease in survival months to be traded for better health) was
6.2 months in the PAC group compared with 0.9 months in the clinical assessment
group. Benefit remained if LV assist device or transplant patients were given
the worst score (P = .03-.05). When the
missing data were modeled using the newly described method of Davidian et
al,23 the results were no longer significant,
but the effects trended in the same direction. The exploratory secondary end
point of direct time trade-off–adjusted survival was dominated by survival
and was neutral.
The ESCAPE trial selected a population more severely compromised than
any other NHLBI-sponsored trial of medical therapy in patients with heart
failure. The addition of PAC monitoring to clinical assessment had no overall
effect on the primary end point. Although there were more adverse events in-hospital
associated with the PAC, there was no excess early mortality. There was a
consistent trend for greater functional improvement after therapy guided by
the PAC.
Neutral Impact of PAC on Primary End Point
The absence of benefit for the PAC on the primary end point could have
resulted from multiple factors listed below, as anticipated in the original
design.18
Previous retrospective studies raised the possibility that the catheter
itself was associated with sufficient adverse events to influence major outcomes.16,24,25 The PAC, as used
by the investigating sites in ESCAPE, appeared overall to be safe. The results
suggest that retrospective reports of excess mortality with PACs were confounded
by the severity of clinical status leading to the decision to use PACs. This
is supported by the more severe clinical compromise in PAC registry patients
in this study (Table 1). In ESCAPE there
were only 9 (4.2%) direct procedural complications, which may reflect both
experienced sites and specific education prior to site enrollment.
Impact of Therapy to Reduce Filling Pressures
In the PAC group, therapy tailored to approach a PCWP of 15 mm Hg and
a right atrial pressure of 8 mm Hg reduced these pressures effectively. Marked
clinical resolution of the signs and symptoms of congestion occurred in both
groups (Table 3), providing a benchmark
for the effectiveness of therapy during hospitalization for heart failure.
The accuracy of skilled investigators in clinical assessment of filling pressures
may have been adequate to identify and monitor the clinical interventions
required without precise hemodynamic confirmation.
The prognostic importance of achieving low PCWP at discharge has been
previously described.26-28 The
relation between filling pressures and mortality likely reflects multiple
interactions with disease progression.29-31 As
in prior experiences, it is not possible to determine whether achievement
of lower filling pressures actually caused better outcomes or merely identified
patients with more favorable outcomes regardless of therapy.
Benefit derived from the PAC might have been offset if knowing hemodynamic
information triggered excess use of medications with deleterious consequences.
Such differences appeared to result from PAC use following surgery.32 Differences in use of intravenous vasoactive agents
did occur in the ESCAPE study and may have affected mortality,33 but
there was no benefit of PAC use on the primary end point, even for patients
who received neither intravenous inotropic nor vasodilator therapy (Table 5). The possibility remains that a potential
benefit of hemodynamic information was obscured by variability in how therapies
were adjusted in response.
Comparison With Previous Results in Advanced Heart Failure
There have been no previous randomized trials of therapy tailored during
continuous hemodynamic monitoring in heart failure. Use of an indwelling PAC
to adjust therapy in advanced heart failure was first described by Kovick
et al34 and subsequently by Pierpont35 for vasodilator therapy in decompensated heart failure
with high systemic vascular resistance. It became common to assess reversibility
of secondary pulmonary hypertension during transplant evaluation, for which
reduction of LV filling pressures is crucial. The approach of tailoring therapy
to reduce filling pressures was then extended to improve clinical status for
patients awaiting or ineligible for transplantation.36 This
approach, combined with intensive outpatient heart failure management, was
associated with reduced hospitalizations, decreased clinical congestion, and
improved exercise capacity.14,37,38 Similar
experiences elsewhere demonstrated recognition of clinically unappreciated
volume overload and improved exercise capacity when therapy was adjusted using
PAC information.39
The advanced heart failure population and therapies have evolved since
these experiences. Decompensation was previously accompanied by severe vasoconstriction,
such that aggressive vasodilation in addition to diuresis was required to
reduce filling pressures.15,40 Patients
now have longer duration of heart failure and ACE inhibitor use prior to advanced
symptoms, and many have received β-blockers. The average systemic vascular
resistance at baseline in ESCAPE was only 1500 dynes × s/cm5, compared with over 1800 dynes × s/cm5 in several
previous experiences.15 However, progression
of renal dysfunction and diuretic resistance more commonly limits therapy
than previously.41,42 The average
discharge furosemide equivalent was 180 mg, compared with less than 100 mg
in earlier experiences.14 Current therapy during
hospitalization for heart failure now may focus less on high filling pressures
with vasoconstriction and more on high filling pressures with renal dysfunction.
There have been 11 previous randomized trials of PACs in critical illness,
in which the goals of therapy diverged from those described here for heart
failure.32,43-46 A
meta-analysis of these trials, including ESCAPE, showed a hazard ratio of
1.00 for mortality and hospitalization.47 The
recently published PAC-Man trial of 1014 patients from varied practice settings
in the United Kingdom also demonstrated no effect on major end points in the
overall population or in the 11% of patients with heart failure.48 These
trials support the safety of PACs and the overall neutral effect, while highlighting
the challenge of assessing a diagnostic tool without a consistent strategy
of response with effective therapies.
Secondary Functional End Points
Function and quality of life are crucial to patients with heart failure,
a chronic debilitating disease. ESCAPE is distinct from other trials of PAC,
which have included patients during acute events with anticipated complete
recovery. As revealed in our patients’ preferences, survival is not
the only, and for some not the most important, metric of benefit. While improvement
in clinical status in both groups was substantial and sustained, a consistent
trend suggested greater improvement in patients in whom therapy had been adjusted
using PACs. This could reflect the close relation between filling pressures
and symptoms of congestion. Exercise capacity has been shown to improve with
reduction of filling pressures beyond that needed to treat edema.38,39 The heart failure questionnaire improvement
was greater by 5 points at 1 month in the PAC group, a level that has been
established as clinically meaningful to patients.20,49
The time trade-off tool has only recently been used to assess patients
with heart failure.21,50,51 Primarily
used in severe illnesses such as cancer, it correlates with functional assessments
and symptom scales, but with marked individual variation. Some patients want
survival at any cost, while others focus more on improving daily life than
prolonging it.21 The improvement in the PAC
group was more than twice as great at every time point, suggesting that the
patients awarded more value to their lives after therapy adjusted to lower
filling pressures. The time trade-off instrument has shown a strong relation
between elevated jugular venous pressure and willingness to trade time for
better health quality.21 In ESCAPE, the average
time to be traded out of 24 months was 9 months at the time of randomization,
confirming that patients with this severity of illness place high value on
improving their quality of life.
Applicability of ESCAPE Results
There were no subgroups identified in which the impact of PAC use was
significantly different from the overall trial. The representation of 175
(40%) minority subjects and 112 (26%) women suggests that similar considerations
apply to PAC use in these groups. The population was defined specifically
to exclude patients in whom PAC insertion seemed likely for urgent management.
ESCAPE centers were specifically selected for experience with clinical
and hemodynamic assessment during therapy for advanced heart failure. The
ESCAPE benchmark for clinical improvement during hospitalization for heart
failure derives from experienced clinicians, recognized to be more accurate
with both physical assessment and interpretation of hemodynamic measurements.52 The safety of the PAC procedure also applies only
to experienced centers, with a trend for better outcomes in those with the
highest enrollment. With the absence of benefit for the primary end point,
there is no rationale at this time to increase the number of centers using
the PAC for the management of heart failure.
Interpretation of the ESCAPE results is limited by the lack of definition
of precise strategy in response to the hemodynamic information obtained. There
was considerable variation between sites in use of medications. Exercise tests,
quality of life questionnaires, and the time trade-off utility assessments
were secondary end points, with missing data that could not be assumed to
occur randomly. Challenge arises in interpreting positive findings among an
array of secondary end points dominated by a neutral primary end point.
Implications for PAC Use in Advanced Heart Failure
Based on ESCAPE, there is no indication for routine use of PACs to adjust
therapy during hospitalization for decompensation of chronic heart failure.
It seems probable that there are some patients and some therapies that yield
improved outcome with PAC monitoring and others with counterbalancing deleterious
effects. The ESCAPE trial does not provide information on using PACs in cardiogenic
shock or in triage for LV assist devices and cardiac transplantation.
For patients in whom signs and symptoms of congestion do not resolve
with initial therapy, consideration of PAC monitoring at experienced sites
appears reasonable if the information may guide further choices of therapy.
In light of accumulating information regarding the deleterious effect of intravenous
inotropic therapy, the PAC might be used to guide therapies for patients in
whom inotropic therapy would otherwise be used.
The ESCAPE trial defined the most compromised patient population to
be studied in an NHLBI heart failure trial with medical therapy, with 19%
(83 patients) mortality at 6 months. No diagnostic test by itself will improve
outcomes. New strategies should be developed to test both the interventions
and the targets to which they should be tailored. Although most trials in
a high-event population have focused on reducing mortality, patients with
advanced heart failure express willingness to trade survival time for better
health during the time remaining. How patients value their daily lives should
help guide both the design and evaluation of new therapies.
Corresponding Author: Lynne W. Stevenson,
MD, Brigham and Women’s Hospital, Cardiovascular Division, Department
of Medicine, 75 Francis St, PBB-1, Boston, MA 02115 (lstevenson@partners.org).
Author Contributions: Dr Stevenson had full
access to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Stevenson, O’Connor,
Califf, Sopko, Shah, Leier.
Acquisition of data: Stevenson, O’Connor,
Califf, Miller, Shah, Hasselblad, Francis, Leier, Binanay.
Analysis and interpretation of data: Stevenson,
O’Connor, Califf, Sopko, Shah, Hasselblad, Francis.
Drafting of the manuscript: Stevenson, O’Connor,
Miller, Shah, Hasselblad.
Critical revision of the manuscript for important
intellectual content: Stevenson, O’Connor, Califf, Sopko, Shah,
Hasselblad, Francis, Leier, Binanay.
Statistical analysis: Hasselblad.
Obtained funding: Stevenson, O’Connor,
Califf, Shah, Leier.
Administrative, technical, or material support:
Califf, Sopko, Shah, Leier, Binanay.
Study supervision: Stevenson, Sopko, Shah.
Financial Disclosures: None reported.
Authors/ESCAPE Executive Committee:Cynthia Binanay, RN, BSN,
Project Leadership, Duke Clinical Research Institute, Durham, NC; Robert M. Califf, MD,
Division of Cardiology, Duke University Medical Center and Duke Clinical Research
Institute, Durham, NC; Vic Hasselblad, PhD, Biostatistics and Bioinformatics,
Duke Clinical Research Center, Durham, NC; Christopher
M. O’Connor, MD,
Division of Cardiology, Duke University Medical Center and Duke Clinical Research
Institute, Durham, NC; Monica R. Shah, MD, MHS, MSJ , Department of Cardiology,
Columbia University Medical Center, New York, NY; George Sopko, MD, MPH, Division
of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, Md; Lynne W. Stevenson, MD, Cardiovascular
Division, Brigham and Women’s Hospital, Boston, Mass.
Authors/ESCAPE Publications Committee:Gary S. Francis, MD,
Coronary Intensive Care Unit, The Cleveland Clinic Foundation, Cleveland,
Ohio; Carl V. Leier, MD, Division of Cardiovascular Medicine, The Ohio
State University, Columbus; Leslie W. Miller, MD, Division of Cardiology,
University of Minnesota, Minneapolis.
ESCAPE Site Investigators, Study Coordinators:University of Florida: James A. Hill, MD/Daniel F. Pauly,
MD, Debra R. Olitsky; Duke University Medical Center:
Stuart Russell, MD/Christopher M. O'Connor, MD, Beth Patterson; LAC-USC: Uri Elkayam, MD, Salman Khan; Brigham and
Women's Hospital: Lynne W. Stevenson, MD, Kimberly Brooks; University of Cincinnati: Lynne Wagoner, MD, Ginger Conway; University of Michigan: Todd Koelling, MD, Carol Van Huysen; Johns Hopkins: Joshua Hare, MD, Elayne Breton; The University of North Carolina: Kirkwood F. Adams, Jr, MD, Jana Glotzer; UCLA: Gregg Fonarow, MD/Michele Hamilton, MD, Julie Sorg; UT Southwestern: Mark Drazner, MD, Shannon Hoffman; University of Minnesota: Leslie W. Miller, MD, Judith A.
Graziano, Mary Ellen Berman; Mayo Clinic: Robert
Frantz, MD, Karen Hartman; The Ohio State University:
Carl V. Leier, MD/William T. Abraham, MD, Laura Yamokoski; Mass General: Thomas G. DiSalvo, MD, Janice Camuso; Northwestern: Mihai Gheorghiade, MD, Karen Fachet; Rush-Presbyterian: Alain Heroux, MD, Soo Jin Kim; University of Calgary: J. Wayne Warnica, MD, Jane Grant; University of Kentucky: Mian Hasan, MD, Lydia Withrow; The Cleveland Clinic Foundation: James Young, MD, Barbara Gus; Vanderbilt University: Javed Butler, MD, Laurie Hawkins; University of Alabama: Barry K. Rayburn, MD, Jessica Robinson; University Hospitals of Cleveland: Ileana Piña,
MD, Lori Shelby; Washington University: Joseph Rogers,
MD, Heidi Craddock; Anaheim Heart: Melvin Tonkon,
MD, Shane Miller; UCSF: Teresa DeMarco, MD, Debra
Lau; University of Wisconsin: Maryl Johnson, MD,
Cassondra Vander Ark.
Operations Team: Wanda Tate, BA, Michael Wilson,
BSPH, Nevia Hayes, Gudaye Tasissa, PhD, Valerie Morrow, MD, and Cynthia Binanay,
RN, BSN, Duke Clinical Research Institute, Durham, NC.
Funding/Support: This research was supported
by contract N01-HV-98177 from the National Heart, Lung, and Blood Institute
to Duke University Medical Center.
Role of the Sponsor: The National Heart, Lung,
and Blood Institute oversaw the formulation and activities of the data and
safety monitoring board. Dr Sopko contributed to the trial design and execution
and participated in the analysis of the data and preparation of the manuscript.
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