beta -Blocker Therapy in Heart Failure
Scientific Review
JAMA. 2002;287:883-889
Author Information <http://jama.ama-assn.org/issues/v287n7/rfull/#aainfo>
JoAnne Micale Foody, MD; Michael H. Farrell, MD; Harlan M. Krumholz, MD
Context Care of patients with heart failure has been revolutionized
throughout the past decade. A paradigm shift in the strategy for treating
heart failure caused by systolic dysfunction is in progress. Despite the
initial perception about beta-blockers' safety, they are now the most
extensively studied class of agents in the treatment of heart failure and
have emerged as an important intervention to improve the clinical outcomes
of heart failure patients.
Objective To provide scientific rationale for the use of beta-blockers for
patients with heart failure.
Data Sources All English-language articles of large, randomized controlled
clinical trials assessing the mortality benefits of beta-blockers in
patients with heart failure were identified to provide the scientific
rationale for the use of beta-blockers in heart failure. Basic science
studies were reviewed to provide an overview of the potential physiologic
role of beta-blockers in heart failure. Finally, clinical guidelines for the
treatment of patients with heart failure were assessed to determine current
recommendations for the use of these agents.
Study Selection and Data Extraction Randomized controlled clinical trials
of beta-blockers that included more than 300 subjects and assessed mortality
as a primary end point.
Data Synthesis Of the 4 beta-blockers tested in large randomized controlled
clinical trials of patients with heart failure, 3 are available in the
United States, bisoprolol, carvedilol, and metoprolol; 2 of these,
carvedilol and metoprolol, have Food and Drug Administration indications for
the treatment of heart failure. Compared with placebo treatment,
beta-blocker use is associated with a consistent 30% reduction in mortality
and a 40% reduction in hospitalizations in patients with class II and III
heart failure.
Conclusions Tested in more than 10 000 patients, beta-blockers reduce
morbidity and mortality in class II through IV heart failure. Along with
angiotensin-converting enzyme inhibitors, digoxin, and diuretics,
beta-blockers have strengthened the armamentarium to improve clinical
outcomes of heart failure patients. The science supporting beta-blockers
must be translated into practice safely and rationally if the agents are to
achieve their full potential.
JAMA. 2002;287:883-889
JSR10002
A medication once thought to be dangerous 1-3
<http://jama.ama-assn.org/issues/v287n7/rfull/#r1> for patients with heart
failure, beta-blockers have been shown to reduce morbidity and mortality 4-9
<http://jama.ama-assn.org/issues/v287n7/rfull/#r4> and are strongly
supported by consensus recommendations and clinical guidelines. 10-12
<http://jama.ama-assn.org/issues/v287n7/rfull/#r10> Clinicians are now
challenged to translate this important new information into clinical
practice.
For half a century, beta-blockers have been an important therapy for
patients with cardiovascular disease. Originally developed as a drug to
treat angina and hypertension, beta-blockers have also become essential
therapies for patients with acute myocardial infarction (AMI) and those with
tachyarrhythmias. Even before beta-blockers were shown to benefit patients
with heart failure, the Nobel Committee declared James W. Black's
development of propranolol as the greatest breakthrough in pharmaceuticals
to treat heart illness since the discovery of digitalis 200 years earlier.
13 <http://jama.ama-assn.org/issues/v287n7/rfull/#r13> , 14
<http://jama.ama-assn.org/issues/v287n7/rfull/#r14>
Enthusiasm for the use of beta-blockers as a treatment for heart failure
emerged slowly. Conventional wisdom held that heart failure was solely due
to a decline in systolic function and was an absolute contraindication for
the prescription of any medication with negative inotropic action. Initial
small studies demonstrating the significant negative inotropic effects and
poor clinical response to beta-blockers 15
<http://jama.ama-assn.org/issues/v287n7/rfull/#r15> , 16
<http://jama.ama-assn.org/issues/v287n7/rfull/#r16> only reinforced this
view. Consequently, early trials of beta-blockers in hypertension or AMI
excluded patients with heart failure. Until recently, national guidelines,
17-20 <http://jama.ama-assn.org/issues/v287n7/rfull/#r17> the US Food and
Drug Administration, and package inserts stated that beta-blockers were
contraindicated in patients with heart failure.
In 1973, Finn Waagstein et al, 21
<http://jama.ama-assn.org/issues/v287n7/rfull/#r21> convinced that the
heart-rate–lowering properties of beta-blockers could provide benefit to
patients with heart failure, administered practolol to a 59-year-old woman
with heart failure, with dramatic improvement in the patient's clinical
status. 22 <http://jama.ama-assn.org/issues/v287n7/rfull/#r22> In another
study, 23 <http://jama.ama-assn.org/issues/v287n7/rfull/#r23> Waagstein and
colleagues demonstrated that beta-blockers were well tolerated by patients
with heart failure. Subsequent studies from his group demonstrated the
clinical benefits of beta-blockers in patients with heart failure. 24
<http://jama.ama-assn.org/issues/v287n7/rfull/#r24> , 25
<http://jama.ama-assn.org/issues/v287n7/rfull/#r25> These studies, however,
did not influence mainstream medical culture, and concerns about the
potential adverse effects of beta-blockers for these patients remained.
Throughout the next 30 years, experts began to perceive that heart failure
was a complex disorder characterized not only by declines in systolic
function, but also by a maladaptive increase in adrenergic drive. 26
<http://jama.ama-assn.org/issues/v287n7/rfull/#r26> , 27
<http://jama.ama-assn.org/issues/v287n7/rfull/#r27> Only after decades of
laboratory science demonstrating biological plausibility, 26-35
<http://jama.ama-assn.org/issues/v287n7/rfull/#r26> mechanistic studies
showing direct cardiovascular effects, 36-41
<http://jama.ama-assn.org/issues/v287n7/rfull/#r36> and large randomized
clinical trials 4-9 <http://jama.ama-assn.org/issues/v287n7/rfull/#r4>
demonstrating mortality benefits did beta-blockers become accepted as a
treatment for heart failure.
This article reviews the scientific rationale supporting the use of
beta-blockers for patients with heart failure and presents current therapy
recommendations 10-12 <http://jama.ama-assn.org/issues/v287n7/rfull/#r10>
based on guidelines from professional organizations. Our goal is to provide
information for clinicians caring for patients with heart failure to
accelerate the appropriate use of beta-blockers for their patients.
Laboratory Science
After the discovery of propranolol, laboratory science laid the groundwork
for beta-blocker use for patients with heart failure 28-35
<http://jama.ama-assn.org/issues/v287n7/rfull/#r28> as it came to be
understood that the pathophysiology of heart failure was related to
activation of the adrenergic nervous system. Early in heart failure, drops
in cardiac output lead to decreased organ perfusion, a compensatory increase
in adrenergic drive, and the subsequent release of neurohormones such as
norepinephrine. 35 <http://jama.ama-assn.org/issues/v287n7/rfull/#r35> , 42
<http://jama.ama-assn.org/issues/v287n7/rfull/#r42> In turn, norepinephrine
stimulates ventricular contraction and increases vascular resistance,
thereby increasing cardiac output and blood pressure. This increase in the
cardiac adrenergic drive, initially a compensatory mechanism for the failing
heart, is one of the earliest measurable responses in heart failure 43
<http://jama.ama-assn.org/issues/v287n7/rfull/#r43> , 44
<http://jama.ama-assn.org/issues/v287n7/rfull/#r44> occurring while
patients are still asymptomatic. 45
<http://jama.ama-assn.org/issues/v287n7/rfull/#r45> , 46
<http://jama.ama-assn.org/issues/v287n7/rfull/#r46>
This chronic activation of the adrenergic nervous system leads to several
potentially deleterious effects on the heart. 47-51
<http://jama.ama-assn.org/issues/v287n7/rfull/#r47> Sustained adrenergic
activation and norepinephrine release raise cardiac output and heart rate,
which then increase myocardial oxygen demand, ischemia, and oxidative
stress. At the same time, peripheral vasoconstriction increases both preload
and afterload, causing additional stress on the failing ventricle. This
long-term mechanical stress in conjunction with cardiac fibrosis 52-55
<http://jama.ama-assn.org/issues/v287n7/rfull/#r52> and necrosis 28-35
<http://jama.ama-assn.org/issues/v287n7/rfull/#r28> promoted by
norepinephrine contributes to cardiac remodeling and a dilated, less
contractile cardiac chamber. Norepinephrine down-regulates the
beta1-adrenergic receptor and uncouples the beta2-adrenergic receptor, 56-58
<http://jama.ama-assn.org/issues/v287n7/rfull/#r56> leaving the myocyte
less responsive to adrenergic stimuli, and further decreases contractile
function. Thus, prolonged activation of the adrenergic system may be
maladaptive, 46 <http://jama.ama-assn.org/issues/v287n7/rfull/#r46> , 59-62
<http://jama.ama-assn.org/issues/v287n7/rfull/#r59> causing progressive
deterioration of myocardial function and portending a poor prognosis. 37
<http://jama.ama-assn.org/issues/v287n7/rfull/#r37> , 41
<http://jama.ama-assn.org/issues/v287n7/rfull/#r41> , 63
<http://jama.ama-assn.org/issues/v287n7/rfull/#r63>
As the neurohormonal hypothesis emerged, so too did a new understanding of
the potential role of beta-blockers in heart failure. Although acute
treatment with beta-blockers decreases blood pressure and cardiac index,
long-term administration of beta-blockers is associated with significant
increases in ejection fraction 64-77
<http://jama.ama-assn.org/issues/v287n7/rfull/#r64> and cardiac index and a
decrease in left ventricular (LV) end diastolic pressure. 61
<http://jama.ama-assn.org/issues/v287n7/rfull/#r61> , 77-87
<http://jama.ama-assn.org/issues/v287n7/rfull/#r77> beta-Blockers reverse
the deleterious changes associated with LV remodeling and decrease
myocardial mass and LV volume, leading to improved hemodynamics. Finally,
beta-blockers may also mediate benefit via regulating heart rate and
decreasing cardiac arrhythmias. 67
<http://jama.ama-assn.org/issues/v287n7/rfull/#r67> These direct cardiac
effects led to the hypothesis that beta-blockers would provide substantial
clinical benefits in patients with heart failure.
Clinical Trials
beta-Blockers have been evaluated in more than 10 000 patients with mild,
moderate, or severe heart failure and ejection fractions less than 40% in
randomized clinical trials. Five meta-analyses 88-92
<http://jama.ama-assn.org/issues/v287n7/rfull/#r88> have arrived at the
same conclusions: the use of beta-blockers was associated with a consistent
30% reduction in mortality and a 40% reduction in hospitalizations in
patients with heart failure. In the most recent of these meta-analyses, 92
<http://jama.ama-assn.org/issues/v287n7/rfull/#r92> it was estimated that
26 patients would need to be treated to avoid 1 death; 25, to avoid 1
hospitalization. Despite differences in patient selection, target doses,
methodology, and clinical end points, results were remarkably consistent
across these trials. The evidence suggests that virtually all patients with
heart failure caused by LV systolic dysfunction benefit from beta-blockers.
Seven mortality trials with more than 300 subjects evaluated the impact of
the second- and third-generation beta-blockers (metoprolol, bisoprolol,
bucindolol, or carvedilol) on patients with symptomatic LV systolic
dysfunction ( Table 1
<http://jama.ama-assn.org/issues/v287n7/fig_tab/jsr10002_t1.html> ). These
trials included the Metoprolol in Dilated Cardiomyopathy (MDC) 93
<http://jama.ama-assn.org/issues/v287n7/rfull/#r93> , 94
<http://jama.ama-assn.org/issues/v287n7/rfull/#r94> study, the Metoprolol
CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF), 6
<http://jama.ama-assn.org/issues/v287n7/rfull/#r6> , 9
<http://jama.ama-assn.org/issues/v287n7/rfull/#r9> the Cardiac
Insufficiency Bisoprolol Studies (CIBIS I and II), 4
<http://jama.ama-assn.org/issues/v287n7/rfull/#r4> , 5
<http://jama.ama-assn.org/issues/v287n7/rfull/#r5> the Australia, New
Zealand, and United States Carvedilol Clinical Trial 8
<http://jama.ama-assn.org/issues/v287n7/rfull/#r8> program, the Carvedilol
Prospective Randomized Cumulative Survival Trial (COPERNICUS), 95
<http://jama.ama-assn.org/issues/v287n7/rfull/#r95> and the Beta-Blocker
Evaluation of Survival Trial (BEST) 96
<http://jama.ama-assn.org/issues/v287n7/rfull/#r96> ( Table 2
<http://jama.ama-assn.org/issues/v287n7/fig_tab/jsr10002_t2.html> ).
One of the earliest controlled trials of beta-blockers in heart failure,
MDC, 93 <http://jama.ama-assn.org/issues/v287n7/rfull/#r93> , 94
<http://jama.ama-assn.org/issues/v287n7/rfull/#r94> was designed to assess
the impact of metoprolol on the combined end point of death or progression
to heart transplantation. In this trial, 383 patients with mild to moderate
heart failure and an ejection fraction less than 40% were randomized to
placebo or metoprolol. Metoprolol initiated at a dose of 5 mg twice daily
and titrated to a high dose of 100 to 150 mg/d was associated with a 34%
decrease in the combined primary end point. Although the improvement was due
entirely to a reduction in the need for cardiac transplantation without a
significant difference in mortality (P = .12), this study was the first
larger-scale trial to add support to the role of beta-blockers in heart
failure therapy. Despite its limitations and negative mortality results, the
MDC trial sparked renewed interest in beta-blockers as a therapy for heart
failure.
In follow-up to the MDC trial, the MERIT-HF 6
<http://jama.ama-assn.org/issues/v287n7/rfull/#r6> , 9
<http://jama.ama-assn.org/issues/v287n7/rfull/#r9> was designed to
determine whether therapy with the long-acting metoprolol CR/XL was
associated with a reduction in all-cause mortality. Larger than the MDC
trial, this study randomized 3991 patients with stable New York Heart
Association class II through IV heart failure and already receiving standard
medical treatment (including angiotensin-converting enzyme [ACE] inhibitors,
diuretics, and digitalis) to increasing doses of metoprolol CR/XL or
placebo. The MERIT-HF trial featured a 2-week placebo run-in period to
assess clinical stability. The starting dosage of metoprolol CR/XL was 12.5
or 25 mg/d and was gradually increased every 2 weeks to the target dose of
200 mg/d. At the conclusion of the study, 64% of the patients were receiving
200 mg of metoprolol per day. Planned follow-up was 2 years, but the study
was stopped early because of a significant decrease in all-cause mortality
in the metoprolol treatment arm. Treatment with metoprolol was associated
with a 34% decrease in all-cause mortality, a 38% decrease in cardiovascular
mortality, a 41% decrease in sudden death, a 49% decrease in death caused by
progressive heart failure, and a 35% reduction in hospitalizations caused by
heart failure. Treatment of 27 patients with metoprolol for 1 year could
prevent 1 death.
At approximately the same time, the CIBIS-I 4
<http://jama.ama-assn.org/issues/v287n7/rfull/#r4> sought to determine
whether bisoprolol therapy was associated with an improvement in survival
and functional status in patients with moderate heart failure and already
receiving diuretics and ACE inhibitors. Although patients treated with
bisoprolol had marked improvements in functional class and reduced
readmissions, the observed difference in mortality between groups did not
reach statistical significance (P = .22; relative risk [RR], 0.80; 95%
confidence interval [CI], 0.56-1.15). In general, CIBIS-I demonstrated the
safety of bisoprolol in patients with moderate heart failure and its
efficacy in improving functional class and decreasing hospitalizations.
The CIBIS-II, 5 <http://jama.ama-assn.org/issues/v287n7/rfull/#r5> with
greater statistical power than its predecessor, CIBIS-I, was designed to
determine whether bisoprolol at optimal target doses of 10 mg/d would be
associated with improved survival. The trial was stopped early after
treatment with bisoprolol was found to have a significant mortality benefit:
156 (11.8%) vs 228 (17.3%) deaths with an RR reduction of 0.66 (95% CI,
0.54-0.81; P<.001) noted in the beta-blocker group. There were significantly
fewer sudden deaths among patients receiving bisoprolol than among those
receiving placebo (48 [3.6%] vs 83 [6.3%] deaths), with an RR reduction of
0.56 (95% CI, 0.39-0.80; P = .001). In addition, all-cause hospital
admission was reduced in the treatment group (hazard ratio, 0.80 [95% CI,
0.71-0.91]; P<.001). Treatment effects were independent of the severity or
cause of heart failure. Of note, CIBIS-II did not have a run-in period and
thus may be more representative of beta-blocker use in clinical practice.
According to these findings, treating 23 patients with bisoprolol would
prevent 1 death.
Carvedilol, a third-generation beta-blocker with alpha1, beta1, and beta2
blocking properties as well as antioxidant activity, was extensively tested
in the US Carvedilol Heart Failure Program, which consisted of different
multicenter trials, 8 <http://jama.ama-assn.org/issues/v287n7/rfull/#r8> ,
81 <http://jama.ama-assn.org/issues/v287n7/rfull/#r81> , 97
<http://jama.ama-assn.org/issues/v287n7/rfull/#r97> each with a run-in
period and including 1094 patients with chronic heart failure. Within each
of the trial protocols, patients with mild, moderate, or severe heart
failure and LV ejection fractions of 35% were randomized to carvedilol (n =
696) or placebo (n = 398). Carvedilol therapy was associated with a
significant reduction in overall mortality rate (3.2% vs 7.8% in the placebo
group). The reduction in mortality was 65% (95% CI, 39%-80%; P<.001).
Carvedilol therapy was associated with a 27% reduction in hospitalizations
for cardiovascular causes (P = .04) and a 38% reduction in the combined end
point of hospitalization or death (P<.001).
In the COPERNICUS, 95 <http://jama.ama-assn.org/issues/v287n7/rfull/#r95>
the first study to target New York Heart Association IIIB to IV patients
with heart failure despite optimal medical therapy, there was a significant
35% decrease in all-cause mortality in patients treated with carvedilol. In
order to address concerns over the safety of these agents in patients with
advanced disease, outcome data were analyzed by high-risk subsets. Even in
patients who had fluid retention, used intravenous inotropes or vasodilators
within 2 weeks, or had 3 heart failure admissions within 1 year, carvedilol
use was associated with a 50% RR reduction in all-cause mortality (95% CI,
27%-90%). Carvedilol was well tolerated at 12 months, with 13% of the
carvedilol-treated patients and 16% of the placebo-treated patients
withdrawing from therapy. According to these results, administering
carvedilol to just 14 patients with severe heart failure would save 1 life.
In contrast to the other recent large trials, the BEST 96
<http://jama.ama-assn.org/issues/v287n7/rfull/#r96> failed to demonstrate
that bucindolol improved overall survival in patients with New York Heart
Association class III to IV heart failure. The data and safety monitoring
board halted this study, which randomized 2708 patients. Patients receiving
bucindolol, a nonselective beta-blocker with vasodilatory properties, showed
a significant decrease in cardiovascular mortality as well as significant
decreases in norepinephrine levels and significant increases in LV function.
Subgroup analysis suggested that black patients may have fared worse with
bucindolol. This result raised questions regarding efficacy of bucindolol in
patients with heart failure as well as concerns that beta-blockers may not
be an effective therapy for black patients with advanced heart failure.
Heart failure patients with recent AMI have also not been extensively
studied. Patients with heart failure were generally excluded from post-AMI
beta-blocker trials, and heart failure patients with recent AMI were
excluded from heart failure beta-blocker trials. The CAPRICORN study 98
<http://jama.ama-assn.org/issues/v287n7/rfull/#r98> was the first large
mortality trial to specifically randomize patients with LV dysfunction
following AMI to assess whether carvedilol in addition to ACE inhibition
would improve all-cause mortality in an era of aggressive reperfusion
therapy. Patients with LV dysfunction (ejection fraction <40%) with or
without heart failure were randomized to carvedilol or placebo early after
an AMI. Patients receiving carvedilol had a lower rate of all-cause
mortality (12% vs 15%), with a hazard ratio of 0.77. The original primary
end point for this study was all-cause mortality. However, because of a
lower-than-anticipated overall mortality in the study sample, a new combined
end point of all-cause mortality or hospital admission for cardiovascular
events was adopted. Although there was no difference in the new primary end
point (35% carvedilol vs 37% placebo), all-cause mortality was lower in
patients receiving carvedilol than in those receiving placebo (12% vs 15%; P
= .03). Although nominally significant for the outcome of all-cause
mortality, P = .03 does not meet the higher level of significance (.005)
established when the primary end point was changed from all-cause mortality
to a combined end point of all-cause mortality and cardiovascular
hospitalizations. In practical terms, however, the observed 23% reduction in
mortality represents a clinically important outcome.
Practice Guidelines
With the emergence of strong new evidence demonstrating that beta-blockers
decrease morbidity and mortality in a broad range of patients with heart
failure, guidelines from the American College of Cardiology and the American
Heart Association, 12 <http://jama.ama-assn.org/issues/v287n7/rfull/#r12>
the European Society of Cardiology, 11
<http://jama.ama-assn.org/issues/v287n7/rfull/#r11> and the Heart Failure
Society of America 10 <http://jama.ama-assn.org/issues/v287n7/rfull/#r10>
all strongly support the use of beta-blockers in patients with heart
failure. The recently published, revised heart failure guidelines of the
American College of Cardiology–American Heart Association 12
<http://jama.ama-assn.org/issues/v287n7/rfull/#r12> and the European
Society of Cardiology clinical practice guidelines 11
<http://jama.ama-assn.org/issues/v287n7/rfull/#r11> recommend use of
beta-blockers in a broader range of heart failure patients, including those
with asymptomatic LV systolic dysfunction and those with severe symptomatic
disease.
These guidelines emphasize that the majority of patients with heart failure
are candidates for beta-blockers, with few exceptions. Currently, only
patients with absolute contraindications to these drugs or patients with
severe heart failure requiring intravenous inotropes or mechanical support
should not receive these agents. Not only are these agents beneficial in
patients with mild to moderate symptomatic heart failure caused by systolic
dysfunction, but also they improve survival in patients with severe
symptomatic heart failure.
Conclusions
Developed nearly half a century ago by Sir James Black, beta-blockers have
become the most extensively scrutinized treatment for heart failure. Basic
science, mechanistic studies, and large, randomized controlled clinical
trials support the value of beta-blockers for patients with heart failure
caused by systolic dysfunction. Tested in more than 10 000 patients, they
reduce morbidity and mortality in class II through IV heart failure. Along
with ACE inhibitors, digoxin, and diuretics, beta-blockers have strengthened
the armamentarium to improve clinical outcomes of heart failure patients.
The science supporting beta-blockers must be translated into practice safely
and rationally if the agents are to achieve their full potential.
Author/Article Information
Author Affiliations: Department of Internal Medicine, Sections of
Cardiovascular Medicine (Drs Foody and Krumholz) and General Medicine (Dr
Farrell), and the Section of Health Policy and Administration, Department of
Epidemiology and Public Health (Dr Krumholz), Yale University School of
Medicine, New Haven, Conn; and the Center for Outcomes Research and
Evaluation, Yale–New Haven Hospital, New Haven, Conn (Dr Krumholz).
Corresponding Author: Harlan M. Krumholz, MD, Yale University School of
Medicine, 333 Cedar St, PO Box 208025, New Haven, CT 06520-8025.
Acknowledgment: We wish to acknowledge the helpful comments of Stephen
Gottlieb, MD, William Abraham, MD, Ed Havranek, MD, Fred Masoudi, MD, and
Javed Butler, MD. We also wish to acknowledge the outstanding editorial
assistance of Ms Maria Johnson.
Financial Disclosure: Dr Krumholz has provided consultation to AstraZeneca
and CV Therapeutics. He has received grant support from Pfizer, Merck,
Sanofi, Biogen, and Bristol-Myers Squibb.
Scientific Review and Clinical Applications Section Editor: Wendy Levinson,
MD, Contributing Editor.
REFERENCES
1. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr1>
Levy JV.
Catecholamine stores and the negative inotropic effect of beta-adrenergic
blocking drugs on the isolated rabbit heart.
Arch Int Physiol Biochim.
1967;75:381-404.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
4167703>
2. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr2>
Nayler WD, Chipperfield D, Lowe TE.
The negative inotropic effect of adrenergic betareceptor blocking drugs on
human heart muscle.
Cardiovasc Res.
1969;3:30-36.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
4391090>
3. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr3>
Epstein S, Robinson BF, Kahler RL, Braunwald E.
Effects of beta-adrenergic blockade on the cardiac response to maximal and
submaximal exercise in man.
J Clin Invest.
1965;44:1745-1753.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
5843708>
4. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr4>
CIBIS Investigators and Committees.
A randomized trial of beta-blockade in heart failure: the Cardiac
Insufficiency Bisoprolol Study (CIBIS).
Circulation.
1994;90:1765-1773.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7923660>
5. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr5>
CIBIS-II Investigators and Committees.
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II).
Lancet.
1999;353:9-13.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10023943>
6. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr6>
The International Steering Committee, MERIT-HF.
Rationale, design, and organization of the Metoprolol CR/XL Randomized
Intervention Trial in Heart Failure (MERIT-HF).
Am J Cardiol.
1997;80:54J-58J.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9375952>
7. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr7>
Cohn JN, Fowler MB, Bristow MR, et al.
Safety and efficacy of carvedilol in severe heart failure: the US Carvedilol
Heart Failure Study Group.
J Card Fail.
1997;3:173-179.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9330125>
8. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr8>
Packer M, Bristow MR, Cohn JN, et al.
The effect of carvedilol on morbidity and mortality in patients with chronic
heart failure: US Carvedilol Heart Failure Study Group.
N Engl J Med.
1996;334:1349-1355.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8614419>
9. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr9>
Goldstein S, Hjalmarson A.
The mortality effect of metoprolol CR/XL in patients with heart failure:
results of the MERIT-HF Trial.
Clin Cardiol.
1999;22(suppl 5):V30-V35.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10526701>
10. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr10>
Heart Failure Society of America (HFSA).
HFSA guidelines for management of patients with heart failure caused by left
ventricular systolic dysfunction.
J Card Fail.
1999;5:357-382.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10634677>
11. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr11>
Remme WJ, Swedberg K.
Guidelines for the diagnosis and treatment of chronic heart failure.
Eur Heart J.
2001;22:1527-1560.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
11492984>
12. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr12>
Hunt SA, Baker DW, Chin MH, et al.
ACC/AHA guidelines for the evaluation and management of chronic heart
failure in the adult: executive summary and recommendations.
J Am Coll Cardiol.
2001;38: 2101-2113.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
11738322>
13. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr13>
Raju TN.
The Nobel chronicles.
Lancet.
2000;355:1022.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10768469>
14. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr14>
Meijler FL.
Sir James Black, FRS, FRCP, FACC.
J Am Coll Cardiol.
1989;13:769-770.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
2537350>
15. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr15>
Currie PJ, Kelly MJ, McKenzie A, et al.
Oral beta-adrenergic blockade with metoprolol in chronic severe dilated
cardiomyopathy.
J Am Coll Cardiol.
1984;3:203-209.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
6140277>
16. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr16>
Ikram H, Fitzpatrick D.
Double-blind trial of chronic oral beta blockade in congestive
cardiomyopathy.
Lancet.
1981;2:490-493.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
6115247>
17. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr17>
Agency for Health Care Policy and Research.
Heart failure: management of patients with left-ventricular systolic
dysfunction.
Clin Pract Guidel Quick Ref Guide Clin.
1994;(11):1-25.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8012418>
18. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr18>
Guidelines for the evaluation and management of heart failure: report of the
American College of Cardiology/American Heart Association Task Force on
Practice Guidelines (Committee on Evaluation and Management of Heart
Failure).
Circulation.
1995;92:2764-2784.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7586389>
19. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr19>
Baker DW, Konstam MA, Bottorff M, Pitt B.
Management of heart failure.
JAMA.
1994;272:1361-1366.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7933398>
20. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr20>
Brooks NH.
Five points from the AHCPR guideline on heart failure.
Am Fam Physician.
1994;50:531-532.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8067317>
21. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr21>
Waagstein F, Hjalmarson AC, Wasir HS.
Apex cardiogram and systolic time intervals in acute myocardial infarction
and effects of practolol.
Br Heart J.
1974;36:1109-1121.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
4451589>
22. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr22>
Waagstein F, Hjalmarson A, Varnauskas E, Wallentin I.
Effect of chronic beta-adrenergic receptor blockade in congestive
cardiomyopathy.
Br Heart J.
1975;37:1022-1036.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
1191416>
23. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr23>
Waagstein F, Hjalmarson AC.
Double-blind study of the effect of cardioselective beta-blockade on chest
pain in acute myocardial infarction.
Acta Med Scand Suppl.
1976;587:201-208.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
3098>
24. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr24>
Waagstein F, Hjalmarson AC.
Effect of cardioselective beta-blockade on heart function and chest pain in
acute myocardial infarction.
Acta Med Scand Suppl.
1976;587:193-200.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
1062128>
25. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr25>
Waagstein F, Reiz S, Ariniego R, Hjalmarson A.
Clinical results with prenalterol in patients with heart failure.
Am Heart J.
1981;102:548-554.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7270401>
26. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr26>
Katz AM.
Future perspectives in basic science understanding of congestive heart
failure.
Am J Cardiol.
1990;66:468-471.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
2201184>
27. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr27>
Katz AM.
Heart failure in 2001: a prophecy.
Am J Cardiol.
1992;70:126C-131C.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
1414889>
28. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr28>
Kappagoda CT, Linden RJ, Scott EM, Snow HM.
Proceedings: the efferent pathway of the reflex increase in heart rate
produced by stimulation of left arterial receptors.
J Physiol (Lond).
1974;242:79P-80P.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
4156368>
29. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr29>
Pool PE, Covell JW, Levitt M, Gibb J, Braunwald E.
Reduction of cardiac tyrosine hydroxylase activity in experimental
congestive heart failure.
Circ Res.
1967;20:349-353.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
6025614>
30. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr30>
Braunwald E.
Alterations in the activity of the adrenergic nervous system in heart
failure.
UCLA Forum Med Sci.
1970;10:289-294.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
4398780>
31. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr31>
Pool PE, Braunwald E.
Fundamental mechanisms in congestive heart failure.
Am J Cardiol.
1968;22:7-15.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
4232344>
32. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr32>
Kramer RS, Mason DT, Braunwald E.
Augmented sympathetic neurotransmitter activity in the peripheral vascular
bed of patients with congestive heart failure and cardiac norepinephrine
depletion.
Circulation.
1968;38:629-634.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
4300395>
33. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr33>
Spann JF Jr, Chidsey CA, Pool PE, Braunwald E.
Mechanism of norepinephrine depletion in experimental heart failure produced
by aortic constriction in the guinea pig.
Circ Res.
1965;17:312-321.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
5834293>
34. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr34>
Braunwald E, Chidsey CA.
The adrenergic nervous system in the control of the normal and failing
heart.
Proc R Soc Med.
1965;58:1063-1066.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
5852681>
35. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr35>
Chidsey CA, Sonnenblick EH, Morrow AG, Braunwald E.
Norepinephrine stores and contractile force of papillary muscle from the
failing human heart.
Circulation.
1966;33:43-51.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
5901758>
36. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr36>
Cohn JN, Rector TS.
Prognosis of congestive heart failure and predictors of mortality.
Am J Cardiol.
1988;62:25A-30A.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
3389302>
37. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr37>
Cohn JN, Levine TB, Olivari MT, et al.
Plasma norepinephrine as a guide to prognosis in patients with chronic
congestive heart failure.
N Engl J Med.
1984;311:819-823.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
6382011>
38. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr38>
Cohn JN.
Plasma norepinephrine and mortality.
Clin Cardiol.
1995;18:I9-I12.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7743697>
39. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr39>
Francis GS, Goldsmith SR, Ziesche SM, Cohn JN.
Response of plasma norepinephrine and epinephrine to dynamic exercise in
patients with congestive heart failure.
Am J Cardiol.
1982;49:1152-1156.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7064841>
40. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr40>
Francis GS, Cohn JN.
The autonomic nervous system in congestive heart failure.
Annu Rev Med.
1986;37:235-247.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
2871803>
41. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr41>
Francis GS, Cohn JN, Johnson G, Rector TS, Goldman S, Simon A.
Plasma norepinephrine, plasma renin activity, and congestive heart failure.
Circulation.
1993;87:VI40-VI48.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8500238>
42. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr42>
Chidsey CA, Braunwald E.
Sympathetic activity and neurotransmitter depletion in congestive heart
failure.
Pharmacol Rev.
1966;18:685-700.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
5904181>
43. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr43>
Minami M, Yasuda H, Yamazaki N, et al.
Plasma norepinephrine concentration and plasma dopamine-beta-hydroxylase
activity in patients with congestive heart failure.
Circulation.
1983;67:1324-1329.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
6851028>
44. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr44>
Pierpont GL, Francis GS, DeMaster EG, et al.
Heterogeneous myocardial catecholamine concentrations in patients with
congestive heart failure.
Am J Cardiol.
1987;60:316-321.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
3303889>
45. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr45>
Rundqvist B, Elam M, Bergmann-Sverrisdottir Y, Eisenhofer G, Friberg P.
Increased cardiac adrenergic drive precedes generalized sympathetic
activation in human heart failure.
Circulation.
1997;95:169-175.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8994433>
46. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr46>
Packer M.
Evolution of the neurohormonal hypothesis to explain the progression of
chronic heart failure.
Eur Heart J.
1995;16(suppl F):4-6.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8521884>
47. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr47>
Francis GS, Benedict C, Johnstone DE, et al.
Comparison of neuroendocrine activation in patients with left ventricular
dysfunction with and without congestive heart failure.
Circulation.
1990;82:1724-1729.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
2146040>
48. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr48>
Levine TB, Francis GS, Goldsmith SR, Simon AB, Cohn JN.
Activity of the sympathetic nervous system and renin-angiotensin system
assessed by plasma hormone levels and their relation to hemodynamic
abnormalities in congestive heart failure.
Am J Cardiol.
1982;49:1659-1666.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7044086>
49. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr49>
Viquerat CE, Kereiakes D, Morris DL, et al.
Alterations in left ventricular function, coronary hemodynamics and
myocardial catecholamine balance with MDL 17043, a new inotropic vasodilator
agent, in patients with severe heart failure.
J Am Coll Cardiol.
1985;5:326-332.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
3155761>
50. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr50>
Viquerat CE, Daly P, Swedberg K, et al.
Endogenous catecholamine levels in chronic heart failure.
Am J Med.
1985;78:455-460.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
3976704>
51. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr51>
Swedberg K, Viquerat CE, Rouleau JL, et al.
Comparison of myocardial catecholamine balance in chronic congestive heart
failure and in angina pectoris without failure.
Am J Cardiol.
1984;54:783-786.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
6486028>
52. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr52>
Mann DL, Cooper G IV.
Neurohumoral activation in congestive heart failure: a double-edged sword?
Clin Cardiol.
1989;12:485-490.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
2571439>
53. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr53>
Mann DL.
Mechanisms and models in heart failure.
Circulation.
1999;100:999-1008.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10468532>
54. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr54>
Mann DL.
Basic mechanisms of disease progression in the failing heart: the role of
excessive adrenergic drive.
Prog Cardiovasc Dis.
1998;41:1-8.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9715817>
55. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr55>
Hasegawa K, Iwai-Kanai E, Sasayama S.
Neurohormonal regulation of myocardial cell apoptosis during the development
of heart failure.
J Cell Physiol.
2001;186:11-18.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
11147805>
56. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr56>
Bristow MR.
Mechanism of action of beta-blocking agents in heart failure.
Am J Cardiol.
1997;80:26L-40L.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9412540>
57. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr57>
Bristow MR, Roden RL, Lowes BD, Gilbert EM, Eichhorn EJ.
The role of third-generation beta-blocking agents in chronic heart failure.
Clin Cardiol.
1998;21:I3-I13.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9853189>
58. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr58>
Feldman AM, Bristow MR.
The beta-adrenergic pathway in the failing human heart: implications for
inotropic therapy.
Cardiology.
1990;77(suppl 1):1-32.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
1970755>
59. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr59>
Bristow MR.
Mechanistic and clinical rationales for using beta-blockers in heart
failure.
J Card Fail.
2000;6:8-14.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10908093>
60. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr60>
Cohn JN.
Is neurohormonal activation deleterious to the long-term outcome of patients
with congestive heart failure? III: antagonist's viewpoint.
J Am Coll Cardiol.
1988;12:554-558.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
2899100>
61. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr61>
Eichhorn EJ.
The paradox of beta-adrenergic blockade for the management of congestive
heart failure.
Am J Med.
1992;92:527-538.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
1349791>
62. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr62>
Ferrari R, Ceconi C, Curello S, Visioli O.
The neuroendocrine and sympathetic nervous system in congestive heart
failure.
Eur Heart J.
1998;19(suppl F):F45-F51.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9651735>
63. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr63>
Rector TS, Olivari MT, Levine TB, Francis GS, Cohn JN.
Predicting survival for an individual with congestive heart failure using
the plasma norepinephrine concentration.
Am Heart J.
1987;114:148-152.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
3604856>
64. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr64>
Anthonio RL, Brouwer J, Lechat P, et al.
Different effects of bisoprolol on heart rate in patients with ischemic or
idiopathic dilated cardiomyopathy (a 24-hour Holter substudy of the Cardiac
Insufficiency Bisoprolol Study [CIBIS]).
Am J Cardiol.
1999;83:1286-1289, A10.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10215303>
65. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr65>
Cohn JN, Johnson GR, Shabetai R, et al.
Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio,
ventricular arrhythmias, and plasma norepinephrine as determinants of
prognosis in heart failure.
Circulation.
1993;87:VI5-V16.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8500240>
66. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr66>
Frankenberger O, Steinberg JS.
Beta-blockers and amiodarone for the primary prevention of sudden cardiac
death.
Curr Cardiol Rep.
1999;1:274-281.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10980854>
67. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr67>
Lechat P, Hulot J-S, Escolano S, et al.
Heart rate and cardiac rhythm relationships with bisoprolol benefit in
chronic heart failure in CIBIS II Trial.
Circulation.
2001;103:1428-1433.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
11245648>
68. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr68>
Barone FC, Campbell WG Jr, Nelson AH, Feuerstein GZ.
Carvedilol prevents severe hypertensive cardiomyopathy and remodeling.
J Hypertens.
1998;16:871-884.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9663928>
69. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr69>
Cohn JN.
Critical review of heart failure.
Clin Cardiol.
1995;18:IV4-IV12.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7489620>
70. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr70>
Jaffe R, Flugelman MY, Halon DA, Lewis BS.
Ventricular remodeling: from bedside to molecule.
Adv Exp Med Biol.
1997;430:257-266.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9330735>
71. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr71>
Patten RD, Udelson JE, Konstam MA.
Ventricular remodeling and its prevention in the treatment of heart failure.
Curr Opin Cardiol.
1998;13:162-167.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9649938>
72. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr72>
Basu S, Senior R, Raval U, van der Does R, Bruckner T, Lahiri A.
Beneficial effects of intravenous and oral carvedilol treatment in acute
myocardial infarction.
Circulation.
1997;96:183-191.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9236433>
73. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr73>
Dernellis JM, Vyssoulis GP, Zacharoulis AA, Toutouzas PK.
Acute changes of left atrial distensibility in congestive heart failure.
Clin Cardiol.
1998;21:28-32.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9474463>
74. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr74>
Doughty RN, Sharpe N.
Beta-adrenergic blocking agents in the treatment of congestive heart
failure.
Annu Rev Med.
1997;48:103-114.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9046949>
75. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr75>
Feldman RL, Prida XE, Hill JA.
Systemic and coronary hemodynamic effects of combined oral alpha- and
beta-adrenergic blockade (labetalol) in normotensive patients with stable
angina pectoris and positive exercise stress tests.
Clin Cardiol.
1988;11:383-388.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
3396239>
76. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr76>
Feldman RL, Prida XE, Lambert CR, Hill JA.
Systemic and coronary hemodynamics of labetalol in normotensive patients
with ischemic heart disease.
Cardiovasc Drugs Ther.
1988;2:355-361.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
3155428>
77. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr77>
Gilbert EM, Abraham WT, Olsen S, et al.
Comparative hemodynamic, left ventricular functional, and antiadrenergic
effects of chronic treatment with metoprolol versus carvedilol in the
failing heart.
Circulation.
1996;94:2817-2825.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8941107>
78. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr78>
Bristow MR, O'Connell JB, Gilbert EM, et al.
Dose-response of chronic beta-blocker treatment in heart failure from either
idiopathic dilated or ischemic cardiomyopathy.
Circulation.
1994;89:1632-1642.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7908610>
79. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr79>
Bristow MR, Gilbert EM, Abraham WT, et al.
Carvedilol produces dose-related improvements in left ventricular function
and survival in subjects with chronic heart failure.
Circulation.
1996;94:2807-2816.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8941106>
80. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr80>
Carson P, Johnson G, Fletcher R, Cohn J.
Mild systolic dysfunction in heart failure (left ventricular ejection
fraction >35%).
J Am Coll Cardiol.
1996;27:642-649.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8606276>
81. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr81>
Colucci WS, Packer M, Bristow MR, et al.
Carvedilol inhibits clinical progression in patients with mild symptoms of
heart failure: US Carvedilol Heart Failure Study Group.
Circulation.
1996;94:2800-2806.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8941105>
82. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr82>
DiBona GF, Sawin LL.
Effect of metoprolol administration on renal sodium handling in experimental
congestive heart failure.
Circulation.
1999;100:82-86.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10393685>
83. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr83>
Hash TW II, Prisant LM.
Beta-blocker use in systolic heart failure and dilated cardiomyopathy.
J Clin Pharmacol.
1997;37:7-19.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9048267>
84. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr84>
Hjalmarson A, Goldstein S, Fagerberg B, et al.
Effects of controlled-release metoprolol on total mortality,
hospitalizations, and well-being in patients with heart failure: the
Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure
(MERIT-HF): MERIT-HF Study Group.
JAMA.
2000;283:1295-1302.
ABSTRACT <http://jama.ama-assn.org/issues/v283n10/abs/joc92053.html> |
FULL TEXT <http://jama.ama-assn.org/issues/v283n10/rfull/joc92053.html> |
PDF <http://jama.ama-assn.org/issues/v283n10/rpdf/joc92053.pdf> |
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10714728>
85. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr85>
McDonald KM, Francis GS, Carlyle PF, et al.
Hemodynamic, left ventricular structural and hormonal changes after discrete
myocardial damage in the dog.
J Am Coll Cardiol.
1992;19:460-467.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
1732376>
86. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr86>
Metra M, Nardi M, Giubbini R, Dei CL.
Effects of short- and long-term carvedilol administration on rest and
exercise hemodynamic variables, exercise capacity and clinical conditions in
patients with idiopathic dilated cardiomyopathy.
J Am Coll Cardiol.
1994;24:1678-1687.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7963115>
87. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr87>
Eichhorn EJ.
Do beta-blockers have a role in patients with congestive heart failure?
Cardiol Clin.
1994;12:133-142.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7910113>
88. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr88>
Avezum A, Tsuyuki RT, Pogue J, Yusuf S.
Beta-blocker therapy for congestive heart failure.
Can J Cardiol.
1998;14:1045-1053.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9738164>
89. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr89>
Lechat P, Packer M, Chalon S, Cucherat M, Arab T, Boissel JP.
Clinical effects of beta-adrenergic blockade in chronic heart failure.
Circulation.
1998;98:1184-1191.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9743509>
90. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr90>
Doughty R, Rodgers A, Sharpe N, MacMahon S.
Effects of beta-blocker therapy on mortality in patients with heart failure.
Eur Heart J.
1997;18:560-565.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9129883>
91. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr91>
Heidenreich PA, Lee TT, Massie BM.
Effect of beta-blockade on mortality in patients with heart failure.
J Am Coll Cardiol.
1997;30:27-34.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
9207617>
92. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr92>
Brophy JM, Joseph L, Rouleau JL.
Beta-blockers in congestive heart failure: a Bayesian meta-analysis.
Ann Intern Med.
2001;134:550-560.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
11281737>
93. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr93>
Waagstein F, Bristow MR, Swedberg K, et al.
Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy:
Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group.
Lancet.
1993;342:1441-1446.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7902479>
94. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr94>
Wiklund I, Waagstein F, Swedberg K, Hjalmarsson A.
Quality of life on treatment with metoprolol in dilated cardiomyopathy:
results from the MDC trial: Metoprolol in Dilated Cardiomyopathy trial.
Cardiovasc Drugs Ther.
1996;10:361-368.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8877080>
95. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr95>
Packer M, Coats AJS, Fowler MB, et al.
Effect of carvedilol on survival in severe chronic heart failure.
N Engl J Med.
2001;344:1651-1658.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
11386263>
96. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr96>
BEST Investigators.
A trial of the beta blocker bucindolol in patients with advanced chronic
heart failure.
N Engl J Med.
2001;344:1659-1667.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
11386264>
97. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr97>
Bristow MR, Gilbert EM, Abraham WT, et al.
Effect of carvedilol on LV function and mortality in diabetic versus
non-diabetic patients with ischemic or non-ischemic dilated cardiomyopathy.
Circulation.
1996;94:I-644.
98. <http://jama.ama-assn.org/issues/v287n7/rfull/#rr98>
Dargie HJ.
Effect of carvedilol on outcome after myocardial infarction in patients with
left-ventricular dysfunction: the CAPRICORN randomized trial.
Lancet.
2001;357:1385-1390.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
11356434>
Edward E. Rylander, M.D.
Diplomat American Board of Family Practice.
Diplomat American Board of Palliative Medicine.
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