Short-term Intravenous Milrinone for Acute Exacerbation of
Chronic Heart Failure
A Randomized Controlled Trial
Michael S. Cuffe, MD; Robert M. Califf, MD; Kirkwood F. Adams, Jr, MD;
Raymond Benza, MD; Robert Bourge, MD; Wilson S. Colucci, MD; Barry M. Massie,
MD; Christopher M. O'Connor, MD; Ileana Pina, MD; Rebecca Quigg, MD; Marc A.
Silver, MD; Mihai Gheorghiade, MD; for the Outcomes of a Prospective Trial of
Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF)
Investigators
Context Little randomized evidence is available to guide the in-hospital
management of patients with an acute exacerbation of chronic heart failure.
Although intravenous inotropic therapy usually produces beneficial hemodynamic
effects and is labeled for use in the care of such patients, the effect of such
therapy on intermediate-term clinical outcomes is uncertain.
Objective To prospectively test whether a strategy that includes short-term
use of milrinone in addition to standard therapy can improve clinical outcomes
of patients hospitalized with an exacerbation of chronic heart failure.
Design Prospective, randomized, double-blind, placebo-controlled trial
conducted from July 1997 through November 1999.
Setting Seventy-eight community and tertiary care hospitals in the United States.
Participants A total of 951 patients admitted with an exacerbation of systolic
heart failure not requiring intravenous inotropic support (mean age, 65 years;
92% with baseline New York Heart Association class III or IV; mean left
ventricular ejection fraction, 23%).
Intervention Patients were randomly assigned to receive a 48-hour infusion of
either milrinone, 0.5 µg/kg per minute initially (n = 477), or saline placebo
(n = 472).
Main Outcome
Measure Cumulative days of
hospitalization for cardiovascular cause within 60 days following
randomization.
Results The median number of days hospitalized for cardiovascular causes
within 60 days after randomization did not differ significantly between
patients given milrinone (6 days) compared with placebo (7 days; P = .71). Sustained hypotension requiring
intervention (10.7% vs 3.2%; P<.001)
and new atrial arrhythmias (4.6% vs 1.5%; P
= .004) occurred more frequently in patients who received milrinone. The
milrinone and placebo groups did not differ significantly in in-hospital
mortality (3.8% vs 2.3%; P =
.19), 60-day mortality (10.3% vs 8.9%; P
= .41), or the composite incidence of death or readmission (35.0% vs 35.3%; P = .92)
CONCLUSION These results do not support the routine use of intravenous
milrinone as an adjunct to standard therapy in the treatment of patients
hospitalized for an exacerbation of chronic heart failure.
JAMA. 2002;287:1541-1547
Chronic heart failure is one of the most common
and life-threatening cardiovascular conditions, affecting nearly 5 million
people in the United States.1 It causes more than
200 000 deaths each year2-4 and is the leading
discharge diagnosis among the Medicare population.5, 6 Treatment costs for
chronic heart failure, most of which are incurred by inpatients, are more than
$30 billion yearly.7 Almost half of the
patients with advanced disease will die within 1 year.8 Hospitalization is
common in these patients and is associated with a poor prognosis.9 From 3 to 6 months
after discharge, readmission rates for chronic heart failure range from 30% to
50%.10-12
Hospitalization for chronic heart failure is
often associated with worsening hemodynamic function,13 which may be partly
responsible for the volume retention that is usually the precipitating factor.
Inotropic agents produce beneficial hemodynamic effects in heart failure
patients and may facilitate earlier achievement of hemodynamic improvement and
titration of standard oral therapy, particularly when used with hemodynamic
monitoring by right-sided heart catheterization.14, 15
Milrinone, a commonly used inotropic agent that
is labeled for use in the short-term intravenous treatment of acute
exacerbation of chronic heart failure, has several characteristics that make it
physiologically attractive. It has both inotropic and vasodilator properties,
which increase cardiac output and reduce systemic vascular resistance and
pulmonary capillary wedge pressures.16 The drug exerts its
hemodynamic effects without excessive changes in heart rate or increases in
myocardial oxygen consumption,16 important because
coronary artery disease and chronic heart failure often coexist.17 Although intravenous
agents (eg, milrinone and dobutamine) are often used as adjuncts to standard
therapy and, with or without hemodynamic guidance, represent a rational
approach to treatment of patients with an acute exacerbation of chronic heart
failure, no placebo-controlled clinical trials have evaluated their proper
role.
The Outcomes of a Prospective Trial of
Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF)
study sought to further evaluate a strategy that includes the short-term use of
milrinone in addition to standard therapy. Although use of milrinone is
indicated for and often used in treatment of patients with heart failure, the
study population of OPTIME-CHF was not in such a severe state (eg, manifesting
cardiogenic shock with end-organ or tissue hypoperfusion) that, in the opinion
of the treating physician, inotropic or vasopressor agents were absolutely
required. The primary hypothesis of this study was that in this population,
short-term treatment with milrinone compared with placebo would result in fewer
days of hospitalization for cardiovascular events within the 60 days following
randomization by either reducing the initial length of stay or preventing
readmission.
METHODS
Study Overview
The design of the study has been described.18 The OPTIME-CHF was a
multicenter, randomized, double-blind, placebo-controlled trial. Patients who
had known systolic chronic heart failure and had been hospitalized for
exacerbation of chronic heart failure no more than 48 hours earlier were
eligible. After approval of each site's institutional review board and written
informed consent was obtained, patients were randomly assigned to receive an
intravenous infusion of either milrinone or saline placebo. To avoid
hypotension, the study drug was administered without a loading dose at an
initial infusion of 0.5 µg/kg per minute, and investigators were encouraged to
continue this rate for 48 hours. The rate could be adjusted downward to 0.375
µg/kg per minute if hypotension or significant improvement occurred and upward
to 0.75 µg/kg per minute if neither occurred. Treatment was to continue for at
least 48 hours and could be continued for up to 72 hours at the discretion of
investigators.
Patients were otherwise treated at the
discretion of their physicians, although recommended guidelines were provided.
Guidelines represented steering-committee consensus of the best conventional
therapy during hospitalization for exacerbation of chronic heart failure,
according to the limited published evidence and outpatient-treatment
guidelines.18 These
guidelines were not a formal part of the protocol but rather recommendations to
be followed with study drug infusion. Critical components of these guidelines
included the initiation and upward titration of angiotensin-converting enzyme
(ACE) inhibitors, adequate diuresis, expeditious conversion to oral therapy,
and comprehensive discharge planning. The target dose of ACE inhibitor was
defined as that shown in randomized trials to reduce mortality, or
dose-equivalent for ACE inhibitors for which mortality data were unavailable.
Follow-up occurred at 30 and 60 days after randomization, in person or by
telephone.
Patients
Eligible patients were at least 18 years of age and had demonstrated left
ventricular ejection fraction below 40% within the past year. Patients were
ineligible if the treating physician judged that intravenous inotropic therapy
was essential (eg, for shock, metabolic acidosis, or severe hypotension).
Patients also were excluded if they had active myocardial ischemia within the
past 3 months, atrial fibrillation with poor ventricular rate control
(>110/min), or sustained ventricular tachycardia or ventricular
fibrillation. Because milrinone is a vasodilator and excreted renally,16 patients with a
baseline systolic blood pressure of less than 80 mm Hg or serum creatinine
level higher than 3.0 mg/dL (265 µmol/L) were excluded.
Study Organization
Patients were recruited at 78 US centers from July 1997 through November 1999.
Institutional review boards at the hospitals approved the protocol and consent
documents. Data management procedures included source data verification of 20%
of all case-report forms, biannual site-monitoring visits, and standard double
data entry. The primary end point of cardiovascular hospitalization was
monitored against source documents for all patients. A steering committee
provided oversight for the scientific conduct of the study. An independent
safety committee reviewed the safety data after 250, 500, and 750 patients had
completed the in-hospital phase of the protocol to ensure the safety of the
active drug and placebo infusion.
Outcomes
The primary efficacy end point was the total number of days hospitalized for cardiovascular
causes (or days deceased) within the 60 days after randomization, a period that
represents the highest risk for heart failure rehospitalization.19 This composite end
point reflects the need to define therapies that safely decrease the length of
index heart failure hospitalization and reduce rehospitalization, which is
common. Acute intravenous hemodynamic therapy was not expected to affect
outcome beyond 60 days. Multisystem disease and social-support problems
frequently coexist with heart failure, and the primary efficacy of this
investigational hemodynamic strategy was evaluated on cardiovascular
hospitalization. Hospital days were defined as inpatient days and emergency
department visit days. Days lost to follow-up and days deceased were
prospectively included in the primary end point to avoid bias toward a therapy
with increased mortality. Site investigators determined whether individual
hospital days were related to cardiovascular causes.
The main secondary outcome included the
proportion of cases failing therapy because of adverse events or worsening
heart failure 48 hours after initiation of therapy. Adverse events included
sustained hypotension, defined as a systolic blood pressure below 80 mm Hg for
more than 30 minutes, requiring intervention; development of myocardial
ischemia; significant atrial arrhythmias; and sustained ventricular arrhythmias
(>30 seconds). Investigators determined worsening heart failure or inadequate
improvement on the basis of persistent pulmonary congestion, inadequate
diuresis, or hypotension with organ hypoperfusion. Other secondary outcomes
included the proportion of patients achieving target doses of ACE-inhibitor
therapy and time to achieve target dose, symptoms, improvement in heart failure
score (Table 1),20 length of initial
hospitalization, days of hospitalization for cardiovascular events from initial
hospital discharge to 60 days, days of hospitalization for cardiovascular
events within 30 days after randomization, all-cause hospitalization, and
mortality.
Statistical Analyses
Analyses were performed with SAS version 6.12 (SAS Institute Inc, Cary, NC) and
S-Plus version 3.4 (Insightful Corp, Seattle, Wash). They included all data
from all but 2 patients randomized (both had withdrawn consent and had been
randomized to the milrinone treatment group) and were performed on an
intent-to-treat basis including all other patients as randomized. Analyses were
conducted at 
= .05 unless
otherwise indicated. For the primary analysis, days with uncertain status
because of lack of follow-up were prospectively and conservatively included as
hospitalized in the primary end point; this principle did not change the
outcome results.
Categorical variables were compared between the
treatment groups with the likelihood ratio 
2 statistic, unless event rates warranted use of the
Fisher exact test. The log-rank test was used to compare survival to 60 days
between the treatment groups. Continuous variables were compared with the
Wilcoxon rank sum test. Treatment groups were compared with a Cox proportional
hazards model for the primary outcome. For patients whose clinical course was
not followed to 60 days, the number of days hospitalized for cardiovascular
causes was augmented by the number of days between the date of death or last
contact and day 60. Cox proportional hazards modeling also was used to compare
the length of initial hospitalization, the number of days patients were
hospitalized for cardiovascular causes between discharge and 60 days, and the
number of days patients were hospitalized (all-cause) within 60 days.
The study was designed with an estimated sample
size of 500 patients per treatment group, based on an 80% power to observe a
clinically meaningful difference of 1 hospital day by using a 2-sided test with
= .05 for
comparison. If the primary end point was normally distributed and given an
anticipated SD of 5 days, at least 392 patients per group would be required if
a 2-sample t test was used.
Safety was determined by blinded monitoring of
treatment failures and serious adverse events. Because both treatment groups
represented accepted care, review of the primary end point occurred only at
trial completion. The proportion of patients with treatment failure or at least
1 serious adverse event between treatment groups was compared by using a
Bayesian approach assuming a noninformative prior.21 The safety committee
was to recommend early termination of the trial to the steering committee if
the Bayesian analyses indicated that P>.95
that the odds ratio of treatment effect for treatment failure or for the rate
of serious adverse events differed from 1.0. Similarly, P>.90 that the odds ratio of treatment
effect differed from 1.0 for mortality was recommended as a guideline for the
safety committee to consider recommending early termination of the trial.
The trial was terminated because of slow
enrollment after 951 patients had been randomized, with the steering committee
and sponsor's agreement after review of the primary end point in
placebo-treated patients. The variance of the distribution of the primary end
point in this group indicated that the study would retain a power of 77%
(compared with 79.5% at 1000 patients) if terminated at the 940 patients
already enrolled in the trial at the time of calculation.
RESULTS
In all, 951 patients were randomized, of whom 2
withdrew consent before treatment, leaving 949 patients available for analysis
(Figure 1).
The 2 groups were well balanced with respect to all but 2 baseline characteristics
(Table 2):
there were a mean 2.1 hospitalizations in the prior year for patients
randomized to milrinone vs 1.9 hospitalizations for patients randomized to placebo
(P = .04), and milrinone-treated
patients were more likely to have been treated with a calcium channel blocker
(15.9% [milrinone] vs 11.2% [placebo]; P
= .03). Similarly, apart from the use of intravenous diuretics at 48 hours
(76.9% [milrinone] vs 82.2% [placebo]; P
= .02), the care of the 2 treatment groups did not differ significantly at
discharge or in regard to the use of medications at 48 hours after
randomization or of major procedures, including right-sided heart
catheterization (Table 3).
Primary efficacy results are shown in Table 4.
Treatment with milrinone did not reduce the primary end point of days
hospitalized for cardiovascular causes within 60 days compared with placebo.
The groups did not differ in the length of the initial hospitalization or
number of days of readmission. The milrinone and placebo groups did not differ
significantly in in-hospital mortality or 60-day mortality. The composite rate
of death or readmission within 60 days was similar in the 2 groups (Table 3).
Clinical status was measured by a composite
heart failure score, a subjective questionnaire on health status (not
previously validated), and a visual analog scale.22 Both groups had a
significant and equivalent reduction in heart failure score from baseline at
day 3 and even more so at discharge. Milrinone-treated patients reported that
they felt better than placebo-treated patients, as measured by the visual
analog scale at one point, 30 days (67 vs 63; P
= .02); no overall significant differences or trends were identified for other
points. There were no differences in procedures between the groups: 5.9% of
patients had invasive hemodynamic monitoring by right-sided heart
catheterization, 2.5% had mechanical ventilation, and 7.0% had left-sided heart
catheterization during the initial hospitalization. There was also no
significant difference between the groups' reaching the target dose of ACE
inhibitor at 48 hours (40.5% milrinone vs 35.8% placebo; P = .14) and at discharge from initial
hospitalization (43.8% milrinone vs 40.9% placebo; P = .36).
Although there was no significant difference in
treatment failures defined by progression of chronic heart failure, treatment
failures caused by adverse events by 48 hours were more common in
milrinone-treated patients (Table 5
and Table 6).
This treatment failure rate reflects the increased incidence of sustained
hypotension and atrial fibrillation in the milrinone-treated patients. During
index hospitalization, serious sustained hypotension (systolic blood pressure
of 
80 mm Hg for at least 30
minutes and requiring intervention) was more common in the milrinone group. Milrinone
use was also associated with new atrial arrhythmias during the index
hospitalization and trended toward an association with more serious ventricular
arrhythmias. Multivariable predictors of any new arrhythmia during the index
hospitalization included milrinone use (P
= .001), lack of previous myocardial infarction (P = .04), use of amiodarone (P = .02), and systolic blood pressure less than 90 mm Hg (P = .047).
In Cox proportional hazards multivariable
analysis, independent baseline predictors of increased days hospitalized
included higher serum urea nitrogen level (P<.001),
lower systolic blood pressure (P<.001),
male sex (P = .008), number of
previous hospitalizations (P =
.002), worse New York Heart Association classification (P = .008), and hyponatremia (P = .03).
COMMENT
The OPTIME-CHF study is, to our knowledge, the
first large, placebo-controlled clinical trial designed to clarify the role of
milrinone, a commonly used intravenous inotropic agent approved by the Food and
Drug Administration in treatment of patients hospitalized for an exacerbation
of chronic heart failure. The underlying rationale for the study was that the
known hemodynamic improvements with short-term intravenous milrinone
administration would translate into clinical benefit measured by shorter
hospitalizations, improved symptoms, or improved dosing of standard therapy. In
this study, however, the routine addition of intravenous milrinone, even though
labeled for this indication, did not demonstrate any benefit in the duration of
hospitalization, dosing of ACE inhibitor, or symptoms. The 48-hour infusion of
milrinone was associated with increased early treatment failures, particularly
caused by new atrial arrhythmias and significant hypotension. This excess of
adverse events did not clearly translate into overall significantly longer
hospitalizations, increased readmission, or mortality.
The clinical characteristics of this population
were typical of patients with worsening chronic heart failure.19 They were generally
older, had significant comorbidities, and showed clinical findings of volume
overload. Nearly all had New York Heart Association class III or IV symptoms at
baseline, had been hospitalized the previous year, and were manifesting
significant signs of persistent volume overload an average of 15 hours after
admission. Such patients with chronic heart failure who required admission
would be treated with intravenous diuresis and titration of standard oral
therapy and, in many cases, with inotropic agents.
Achieving better hemodynamics earlier in
hospitalization might allow increases in ACE inhibitor dose to more desirable
levels before discharge. Some evidence suggests that the short-term use of
milrinone can aid in the upward titration of ACE inhibitors to doses known to
improve outcomes.15, 23 If true, long-term
benefits could result. In this trial, however, ACE inhibitor dosing was not
significantly improved with active milrinone treatment.
Regardless of hemodynamic improvement or impact
on length of stay, drug efficacy must be balanced with safety. Survival in
chronic heart failure relates more closely to severity of left ventricular
dysfunction, neurohormonal abnormalities, and the extent and progression of
coronary disease than to hemodynamics.17 Hospitalization more
closely relates to worsening of the hemodynamic profile and volume retention,
often the result of a high-sodium diet, hypertension, ischemia, or a
combination of these. Particular concern remains over the risks associated with
positive inotropic agents: studies with drugs of this and similar classes have
shown that short-term improvements in hemodynamics may correlate inversely with
mortality.24 Most agents
studied have a common mechanism of action that results in elevated myocardial
cyclic adenosine monophosphate through either 
-receptor
agonism or phosphodiesterase inhibition. Although these agents are
hemodynamically effective with short-term use, their long-term use, including
use of oral milrinone, particularly in patients with more advanced chronic
heart failure, has been strongly associated with increased mortality or
morbidity.25
The OPTIME-CHF study had several limitations. It
did not directly address patients with acutely decompensated chronic heart
failure for whom inotropic therapy was felt to be essential (eg, low cardiac
output state with tissue hypoperfusion), although this is an area in which
physicians may disagree. For all patients, milrinone was used within its
labeled indication. This study was not structured to assess patients for
self-limited ventricular tachycardia, a known adverse effect of milrinone.
Although the excess adverse events did not result in significantly increased
mortality, this study was inadequately powered to evaluate mortality.
CONCLUSION
The OPTIME-CHF study enrolled a population of
patients with severe chronic heart failure and for whom inotropic therapy was
indicated but not, in the opinion of the investigators, essential. Literature
and practice suggest that the patients enrolled in this study are typical of
heart failure patients admitted to US hospitals. No benefit from milrinone
treatment was observed in hospital days, other measurements of chronic heart
failure improvement, or the ability to institute oral drugs that improve long-term
prognosis, although milrinone caused an increase in early adverse events
related to hypotension and atrial arrhythmias. Our results do not support the
routine use of milrinone in patients hospitalized with an exacerbation of
chronic heart failure.
Author/Article Information
Author Affiliations: Duke Clinical
Research Institute, Durham, NC (Drs Cuffe, Califf, and O'Connor); Heart Failure
Program, University of North Carolina, Chapel Hill (Dr Adams); University of
Alabama, Birmingham (Drs Benza and Bourge); Boston University School of
Medicine, Boston, Mass (Dr Colucci); Veterans Affairs Medical Center, San
Francisco, Calif (Dr Massie); University Hospital of Cleveland, Cleveland, Ohio
(Dr Pina); Christ Hospital and Medical Center, Oak Lawn, Ill (Dr Silver); and
Northwestern University, Chicago, Ill (Drs Quigg and Gheorghiade).
Corresponding Author and Reprints:
Mihai Gheorghiade, MD, Northwestern University Medical School, Division of
Cardiology, 201 E Huron St, Galter 10-240, Chicago, IL 60611 (e-mail: [log in to unmask]).
Financial Disclosure: All authors served as consultants for Sanofi-Synthelabo Inc,
received grants or honoraria from the company, or both.
Author Contributions: Dr Gheorghiade, as principal investigator of the study, had full
access to all of the data in this study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Study concept and design: Cuffe, Califf, O'Connor, Gheorghiade.
Acquisition of data: Cuffe, Califf, O'Connor, Gheorghiade.
Analysis and interpretation of
data: Cuffe, Califf, Adams,
Benza, Bourge, Colucci, Massie, O'Connor, Pina, Quigg, Silver, Gheorghiade.
Drafting of the manuscript: Cuffe, Califf, O'Connor, Gheorghiade.
Critical revision of the
manuscript for important intellectual content: Cuffe, Califf, Adams, Benza, Bourge, Colucci, Massie, O'Connor,
Pina, Quigg, Silver, Gheorghiade.
Statistical expertise: Cuffe, Califf, Adams, Benza, Bourge, Colucci, Massie, O'Connor,
Pina, Quigg, Silver, Gheorghiade.
Obtained funding: Califf, Gheorghiade.
Administrative, technical, or
material support: Cuffe, Califf, O'Connor,
Gheorghiade.
Study supervision: Cuffe, Califf, Gheorghiade.
Funding/Support: This investigator-initiated study was designed and conducted by
the steering committee and Duke Clinical Research Institute, Durham, NC. The
study was sponsored by Sanofi-Synthelabo Inc, New York, NY.
Role of Sponsor: The study sponsor, Sanofi-Synthelabo Inc, assisted in the initial
design of this study and helped oversee its conduct to ensure the study's
timely completion. The independent steering committee had complete scientific
oversight throughout the study design and completion. Data analysis was
conducted independent of the study sponsor by the Duke Clinical Research
Institute. The study sponsor and steering committee provided written comment
that was considered by the authors for the manuscript.
OPTIME-CHF Investigators
Steering Committee: M. Gheorghiade (chair), R. M. Califf (cochair), K. F. Adams, Jr,
W. S. Colucci, C. M. O'Connor, R. Quigg, R. Bourge, B. M. Massie, I. Pina, and
M. A. Silver.
Main Writing Committee: M. S. Cuffe, R. M. Califf, C. M. O'Connor, and M. Gheorghiade.
Safety Committee: S. Goldstein (chair), F. E. Harrell, Jr, and L. W. Stevenson.
Sanofi-Synthelabo
Representatives: A. Akbary and J.
Kocsis.
Statistical Analysis: J. D. Leimberger.
Study Coordinators: K. Lucas and L. Robinson.
Clinical Sites and
Investigators: University of Alabama,
Birmingham: R. Benza; St Thomas Hospital, Nashville, Tenn: D. Pearce; Duke
University Medical Center, Durham, NC: C. O'Connor, M. Cuffe; Henry Ford
Hospital, Detroit, Mich: S. Borzak; William Beaumont Hospital, Royal Oak, Mich:
G. Timmis; Georgia Baptist Medical Center, Atlanta: L. Berger; Baptist Medical
Center-Princeton, Birmingham, Ala: M. Wilensky; Osf Saint Francis Medical
Methodist Medical Center,
Peoria, Ill: A. Chu; Deborah Heart & Lung Center, Brown Mills, NJ: R.
Bender; Sacred Heart HospitalBaptist Hospital
Behavioral Medicine Center, Pensacola, Fla: S. Teague; Northeast Medical
Center, Concord, NH: P. Campbell; LSU Medical Center, Shreveport, La: F.
Sheridan; Medical University of South Carolina, Charleston: G. Hendrix;
Northwestern Memorial Hospital, Chicago, Ill: M. Johnson; Hennepin County
Medical Center, Minneapolis, Minn: B. Bart; Saint Luke's Hospital, Kansas City,
Mo: D. Bresnahan; University Hospital, Augusta, Ga: B. Chandler; Margaret R.
Pardee Memorial Hospital, Hendersonville, NC: P. Goodfield;
Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill: W. Kao; James H.
Haley Veterans Affairs Hospital, Tampa, Fla: D. Schocken; John L. McClellan
Veterans Affairs Medical Center and University Hospital of Arkansas for Medical
Sciences, Little Rock: E. Smith; North Shore University Hospital, Manhasset,
NY: D. Grossman; Michigan Heart and Vascular Institute, Ypsilanti: M. Leonen;
Saint Vincent Hospital and Health Care Center, Indianapolis, Ind: E. Fry;
Washington University-Barnes Jewish Hospital, St Louis, Mo: J. Rogers;
Jefferson Hospital, Pittsburgh, Pa: S. Tauberg; Lawrence Memorial Hospital,
Lawrence, Kan: K. M. Zabel; Williamsport Hospital & Medical
Center-Susquehanna Heart Center, Williamsport, Pa: J. Burks; Robert Wood
Johnson University Hospital, New Brunswick, NJ: R. Hilkert; Cedars-Sinai
Medical Center, Los Angeles, Calif: R. Davidson; Medical College of Virginia,
Richmond: M. Hess; Baptist Memorial Hospital, Memphis, Tenn: F. McGrew; Loyola
University Medical Center, Maywood, Ill: J. Mendez; Abbott Northwestern
Hospital, Minneapolis, Minn: M. Pritzker; Good Samaritan Regional Medical
Center, Phoenix, Ariz: E. Selsky; Wuesthoff Hospital, Rockledge, Fla: K.
Sheikh; Evanston Hospital, Evanston, Ill: R. Williams; South Jersey Hospital
System, Elmer, NJ: J. Kramer; Oakwood Hospital and Medical Center, Dearborn,
Mich: A. Riba; Chesapeake General Hospital, Chesapeake, Va: C. Ashby;
Westchester County Medical Center, Valhalla, NY: R. Belkin; Sarasota Memorial
Hospital, Sarasota, Fla: M. Frey; Harper Hospital, Detroit, Mich: P. Gordon;
Virginia Beach General Hospital, Virginia Beach, Va: S. Jones; University of
Minnesota, Minneapolis: L. Miller; Columbia University Hospital, Tamarac, Fla:
R. Schneider, L. Simkins; Mercy Hospital of Pittsburgh, Pa: P. Bannon;
Providence Hospital, Mobile, Ala: C. Brown; North Ridge Medical Center, Ft
Lauderdale, Fla: L. Cioci; Medical Center of Delaware, Newark: E. Marshall;
Roper Hospital, Charleston, SC: B. Reeves; Lutheran General Hospital, Park
Ridge, Ill: L. Brookfield; University of Pennsylvania Medical Center, Braddock:
S. Tauberg; Jewish Hospital, Louisville, Ky: J. Adams; Columbia-Blake Hospital,
Bradenton, Fla: S. Mehanny; Riverside Methodist Hospital, Columbus, Ohio: R.
Frazier; University of Utah Health Science Center, Salt Lake City: D. Renlund;
Illinois Masonic Medical Center, Chicago: C. Chiu; Mary Washington Hospital,
Fredericksburg, Va: T. Martyak; Tulane University School of Medicine, New Orleans,
La: H. Ventura; Memorial Hospital, Chattanooga, Tenn: K. Wright; University of
North Carolina, Chapel Hill: K. Adams; University of Illinois Medical Center,
Chicago: S. Dunlap; Lakeview Regional Medical Center, Covington, La: M. Gomez;
Mount Sinai Medical Center, New York, NY: M. Kukin; Louis A. Weiss Memorial
Hospital, Chicago, Ill: A. Sheikh; Glenbrook Hospital, Glenview, Ill: R.
Williams; Allegheny University Hospital-Graduate, Philadelphia, Pa: B. Berger;
Middletown Regional Hospital, Middletown, Ohio: G. Brown; Morton Plant
Hospital, Clearwater, Fla: M. Hepp; Christ Hospital, Cincinnati, Ohio: D.
Kereiakes; Bayfront Medical Center, St Petersburg, Fla: M. McIvor; Erlanger
Medical Center, Chattanooga, Tenn: M. Mutter; Sentara Hampton General Hospital,
Hampton, Va: K. Newby; Latter-Day Saints Hospital, Salt Lake City, Utah: D.
Renlund; and Madigan Army Medical Center, Tacoma, Wash: M. Yandel.
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Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.