Crit Care Nurs Q

Vol. 30, No. 4, pp. 299–306

Copyright  c 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Pharmacological Treatment of
Heart Failure
Beverly Quinn, MSN, RN

This article provides an overview of heart failure (HF) and pharmacological treatment of systolic
left ventricular dysfunction. The purpose of this article is to provide nurses the knowledge of cur-
rent treatment recommendations and the Five Million Lives campaign sponsored by the National
Institute of Healthcare Improvement. This initiative is a national campaign to protect 5 million
patients from medical harm by promoting evidence-based standards of practice to improve the
healthcare of Americans. HF has become part of this national initiative and the National Institute
of Healthcare Improvement in conjunction with the American College of Cardiology/American
Heart Association has implemented guidelines to improve the care of HF patients. Nurses would
be expected to be familiar with these guidelines, as regulatory agencies will be using these guide-
lines as a benchmark to evaluate the quality of care provided to patients with this diagnosis.
Key words: key indicators, left ventricular heart dysfunction, renin-angiotensin-aldosterone
system

A CCORDING to the American Heart As-

sociation (AHA), congestive heart failure
(CHF) affects approximately 5 million people
in the United States. There are 550 000 new
cases diagnosed each year, and 6.5 million
hospital days are used for management of the
disease yearly. These numbers are expected to
increase with the growth in our elderly popu-
lation over the next decade.1
The Joint Commission, the Centers for
Medicare and Medicaid Services, and the
Institute for Healthcare Improvement (IHI)
have collectively agreed that evidence-based
medicine is the best method for standardizing
healthcare practices that have demonstrated
improvement of morbidity and mortality rates
for specific diseases common in the United
States. These standards of care are evaluated
by core measures or indicators used to bench-
mark an institution’s performance in provid-
ing disease specific care. These data will be
collected by the Joint Commission and the
Centers for Medicare and Medicaid Services
Author Affiliation: Scripps Memorial Hospital
Encinitas, Encinitas, California.
Corresponding Author: Beverly Quinn, MSN, RN,
Scripps Memorial Hospital Encinitas, 354 Santa Fe Dr,
Encinitas, CA 92024 (Bevquinn1@sbcglobal.net).
and publicly reported. Future reimbursement
to healthcare organizations will be based on
the institution’s ability to meet these stan-
dards. Because of the increased prevalence
rate and heightened awareness of CHF, the
IHI has included “Improved care for the pa-
tients with CHF”as part of its Five Million Lives
campaign.2 This campaign is a national initia-
tive to improve quality of American health-
care by shielding patients from 5 million
incidents of medical harm. Part of this ef-
fort utilizes evidence-based practices and the
guidelines for the care of patients with CHF
in conjunction with the American College of
Cardiology (ACC) and the AHA 2005 Clin-
ical Performance Measures for Adults with
Chronic Heart Failure.2
In the 2006, the IHI has identified 7 key indi-
cators of quality measures: left ventricular sys-
tolic heart function assessment; angiotensin-
converting enzyme (ACE) inhibitors or
angiotensin receptor blockers (ARBs) at
discharge for HF patients with left ventricular
systolic dysfunction; anticoagulant for CHF
patients with chronic or recurrent atrial fib-
rillation; record of influenza; pneumococcal
immunization; smoking cessation counseling;
and discharge instructions including activity
level, diet, discharge medications, follow-up
appointment, weight monitoring, and what
299
300 CRITICAL CARE NURSING QUARTERLY/OCTOBER–DECEMBER 2007
to do if symptoms worsen.2 Although it is im-
portant for nurses to have knowledge of these
7 key indicators and the rational behind the
medical treatment of this population set, this
article focuses on the pharmacological treat-
ments used for symptoms of HF and reduced
left ventricular ejection fraction (LVEF).
PATHOPHYSIOLOGY OF HF
Current therapies for the treatment of HF
are aimed at regression and prevention of left
ventricular dysfunction. HF is currently de-
fined as a clinical syndrome characterized by
symptoms of pump failure secondary to struc-
tural and functional disorders that impairs the
ability of the ventricle to fill or eject blood.3,4
Alterations in hemodynamics and neurohu-
moral balance are the major culprits in the de-
velopment of ventricular dysfunction. HF can
affect both ventricles; however, this article fo-
cuses on reduced LVEF and its pharmacologi-
cal approach to treatment. It is important to
understand the type of HF the patient has,
as therapeutic goals may differ for individuals
who do not have reduced LVEF.
Depending on the primary etiology, HF can
manifest itself as systolic or diastolic dys-
function. Systolic dysfunction is characterized
by changes in left ventricular contractility in
which LVEF is less than 0.40; this is character-
ized by the thinning of the heart wall and dila-
tion of filling chamber. The end result is the el-
evated left ventricular filling pressure, which
leads to fluid overload and elevated pressures
in left atrium and pulmonary vasculature. In-
creased left heart and pulmonary pressures
cause fluids to escape into the pulmonary
interstitial spaces, leading to pulmonary
congestion. The elevation of pulmonary pres-
sure leads to increased right-sided heart pres-
sures, and subsequently symptoms of right-
sided HF.3
Diastolic dysfunction is the impairment of
left ventricular relaxation, which decreases
filling of the ventricle during diastole. Ventric-
ular contractility and LVEF are usually normal;
the problem is a filling defect. Diastolic dys-
function is characterized by concentric wall
thickness, which leads to decreased compli-
ance in wall motion and decreased size of the
filling chamber.4
The contributing factors that lead to the de-
velopment of HF are considered the precursor
to the vicious cycle of events that cause the
remodeling of the heart muscle. These events
include uncontrolled hypertension, myocar-
dial infarction, valvular disease, and atrial fib-
rillation. Essentially, any insult that results in a
compensatory rise in the left ventricular end
diastolic filling pressure can lead to the activa-
tion of neurohumoral responses.3,4
Activation of the sympathetic nervous
system (SNS) and the renin-angiotensin-
aldosterone system causes the retention of
sodium and water by the release of rennin
from the distal tubules of the kidney. This
process triggers vasoconstriction, which
continues to perpetuate the release of hor-
mones that contributes to the development
of HF. Renin converts angiotensinogen to
angiotensin I. Angiotensin I is converted
to angiotensin II by ACE, which potentates
vasoconstriction. The increased level of
angiotensin II triggers the adrenals glands to
release aldosterone, an antidiuretic hormone.
Aldosterone, in turn, causes the kidneys
to retain more sodium and water, which
continues to increase the circulating volume.
As the cardiac output decreases and the
circulating levels of angiotensin II increase,
the posterior pituitary gland is stimulated to
release vasopressin. Vasopressin promotes
vasoconstriction and fluid retention; in
response to impaired release of nitric oxide,
the endothelial lining of the vessels releases
an endothelin hormone, which increases
vasoconstriction.
The retention of fluids increases the stretch-
ing of myocardial tissue, which stimulates the
release of natriuretic peptides.3,4
There are 2 natriuretic peptides that are
released by the heart in response to the
increased filling pressures or stimulation of
stretch receptors located in the heart. One
is human atrial natriuretic hormone (hANP),
which is released by receptors located in the
atria, and the other is human brain natriuretic
 Pharmacological Treatment of Heart Failure
hormone (hBNP) released from receptors lo-
cated in the ventricles. Both of these hor-
mones stimulate the kidneys to increase the
excretion of sodium and water in an effort
to decrease the circulating volume. The re-
lease of hBNP also promotes vasodilatation of
veins, arteries, and coronary arteries, which
decreases preload and afterload, which, in
turn, reduces blood pressure.3,4
Over time the body’s compensatory re-
sponses fail, which leads to stiffening of the
endothelial layer of blood vessels and the
heart, causing the tissue to become noncom-
pliant, which promotes ventricular remod-
eling. As the cycle of events continues, it
perpetuates the signs and symptoms of HF,
which can lead to repeated hospital admis-
sions for the treatment of acute symptoms.
Understanding the underlying mechanisms
that lead to HF can help demystify the cur-
rent evidence-based guidelines. It will allow
nurses to understand the rational behind the
drug therapy and treatment standards recom-
mended by the ACC/AHA and the IHI, while
improving care for HF patients.
PHARMACOLOGICAL TREATMENT OF HF
To understand recommendations for drug
treatment, it is necessary to have knowledge
of the classification of recommendations and
levels of evidence system that have been as-
signed by the ACC/AHA guidelines. These rec-
ommendations are based on multiple clinical
trials and are relevant to the size of the popu-
lation studied.5
Classification of recommendations assigns
an estimated value to the effectiveness of the
treatments. The ACC/AHA classification sys-
tem ranks treatment effectiveness from class
I to class III. Class I recommendations sup-
port the use of a particular procedure or treat-
ment as being beneficial, useful, and/or ef-
fective based on the evidence and/or general
agreement of the data. Class II recommen-
dations indicate that there is conflicting evi-
dence and/or a divergence of opinion about
the usefulness or efficacy of a procedure or
therapy. Class II has 2 subdivisions: class IIa
301
states that the evidence or opinion is in favor
of the usefulness or efficacy of the data. Class
IIb states that the evidence or opinions are not
well established. Class III recommendations
do not support use, since the procedure or
therapy is not effective, and may be harmful.5
Levels of evidence examine the number of
study groups involved in the clinical trials or
analyses, which determines the generalized
application of the recommendations on the
size and types of populations studied. Lev-
els of evidence are graded from A through
C. Level A means that the data are derived
from multiple random clinical trials or meta-
analyses. This level of evidence provides more
validity across diverse population sets. Level B
data are obtained from a single random trial or
nonrandomized studies; these studies are lim-
ited to the population used to conduct the re-
search. Level C states that recommendations
are based on the consensus opinion of ex-
perts, case studies, or standards of care.5
CURRENT PHARMACOLOGICAL
TREATMENT
Lifestyle changes and the use of medica-
tions are the primary means for prevention
and regression of left ventricular dysfunction.
The frequency of rehospitalizations can be de-
creased if patients are compliant with their
medication and monitoring based on their
plan of care. Patients need to be educated on
their medications prior to discharge from the
hospital, with nurses playing an intricate part
in this process.
ACE inhibitors
The first-line drug of choice is an ACE in-
hibitor, with a class I, level A of evidence rec-
ommendation, which causes a positive effect
on cardiac function by reducing preload and
afterload, while increasing cardiac output and
ejection fraction.5 The mechanism of action
is vasodilation of both the venous and arte-
rial sides of the heart. ACE inhibitors are ef-
fective in managing HF by interrupting the
stimulation of renin-angiotensin-aldosterone
system. The specific properties of ACE
302 CRITICAL CARE NURSING QUARTERLY/OCTOBER–DECEMBER 2007

Table 1. Selected pharmacological treatment for heart failure

Initial Titrated Adverse

dosing daily maximum dose effects

ACE inhibitors
Captopril 6.25 mg 3 times 50 mg 3 times Cough, hypotension,
hyperkalemia, loss of taste,
leucopenia, angioedema,
rash
Enalapril 2.5 mg twice 10–20 mg twice Same as above
Fosinopril 5–10 mg once 40 mg once Same as above
Lisinopril 2.5–5 mg once 20–40 mg once Same as above
Perindopril 2 mg once 8–16 mg once Same as above
Quinapril 5 mg twice 20 mg twice Same as above
Ramipril 1.25–2.5 mg once 10 mg once Same as above
Trandolapril 1 mg once 4 mg once Same as above
β-Blockers
Carvedilol 3.125 mg twice 25 mg twice, 50 mg Bradycardia, CHF, postural
twice, if patient >85 kg hypotension, atrioventricular
block, fatigue, depression,
bronchospasm, impotence,
decreased exercise tolerance
Bisoprolol 1.25 mg once 10 mg once Same as above
Metoprolol 12.5–25 mg once 200 mg once Same as above
ARBs
Candesartan 4–8 mg once 32 mg once
Losartan 25–50 mg once 50–100 mg once
Valsartan 20–40 mg twice 160 mg twice

Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CHF, congestive heart failure.

inhibitors allow them to bind to active sites
of ACE, which block the conversion of an-
giotensin I to angiotensin II, both of which are
potent vasoconstrictors. The inhibition of an-
giotensin II decreases aldosterone-mediated
sodium and water retention by the kidneys,
which decreases the circulating volume. The
reduction in volume decreases ventricular
end diastolic pressure (preload), which in-
directly produces vasodilation and decreases
systemic vascular resistance (afterload). In
turn, cardiac output increases and patients ex-
perience a decrease of their HF symptoms.4
ACE inhibitors are initiated at low doses
followed by gradual increases if lower doses
are well tolerated. Renal function and serum
potassium level should be monitored 1 to
2 weeks after starting therapy and then pe-
riodically (Table 1). ACE inhibitors should
be used with caution in patients with very
low systemic blood pressures (systolic pres-
sure <80 mm Hg), increased serum crea-
tinine level above 3 mg/dL, bilateral renal
artery stenosis, and serum potassium levels
above 5.5 mmol/L. Patients should not re-
ceive an ACE inhibitor if they have experi-
enced angioedema or renal failure symptoms
with previous use of the drug, or if they are
pregnant.4,6
The most common adverse effects of ACE
inhibitors are headaches, dizziness, fatigue, di-
arrhea, coughing, and hypotension. The most
frequent of these adverse effects is cough-
ing. Patients describe their cough as dry and
nagging, which is reversible once the drug has
been discontinued. If the side effects can be
 Pharmacological Treatment of Heart Failure
tolerated the patient should be encouraged to
stay on the ACE inhibitor, as its benefits out-
weigh the adverse effects.4,6
β-Blockers
β-Blockers, specifically carvedilol, bisopro-
lol, and metoprolol, are recommended as a
class I, level A of evidence for the treat-
ment of HF with reduced LVEF.5 Historically,
β-blockers had been contraindicated for the
treatment of HF. The combination of their
negative inotropic effect, bradycardia, and pe-
ripheral vascular constriction can exacerbate
signs and symptoms of HF. However, the re-
sults from recent experimental and controlled
clinical trails suggest that prolonged activa-
tion of the SNS can accelerate the progression
of HF, which is where β-blockers are helpful.7
These agents decrease the effects of the SNS
on the heart and blood vessels. Activation of
the SNS causes the release of catecholamines,
which triggers cellular changes that promote
the loss of myocardial cells. These cells lead
to cell death (apoptosis). β-Blockers decrease
the adrenergic effects generated by this
process. Both carvedilol and metoprolol have
been shown to improve left ventricular func-
tion, hemodynamics, and symptoms of HF.8
Multiple clinical trials demonstrated a 65% re-
duction in death rates when using carvedilol
versus placebo.8 The clinical trials on
β-blockers were performed on patients re-
ceiving ACE inhibitor therapy. ACE inhibitors
are still the preferred first-line agent, how-
ever, evidence supports the combined use of
both agents.7,8
Initiation of β-blockers therapy starts with
the lowest dose possible to prevent symptoms
of excessive vasodilation such as hypotension,
dizziness, or lightheadedness. Blood pressure
should be closely monitored during treat-
ment. Drug titration should be done slowly,
doubling the dose each time. β-Blockers may
cause fluid retention after 3 to 5 days of start-
ing initial dose (Table 1). Diuretic therapy
can be added or adjusted to treat this initial
fluid retention until weight returns to pre-
treatment levels. Taking the β-blocker, ACE in-
303
hibitor, or vasodilator at different times dur-
ing the day can reduce the risk of developing
hypotension.5,6
β-Blockers are contraindicated in patients
who experience bronchospasm, symptomatic
bradycardia, or advanced heart blockage with-
out pacemaker backup. Liver functions need
monitoring, as rare cases of hepatic injury
have been reported with carvedilol. It is im-
portant for patients to understand that initial
effects of early therapy usually do not pre-
clude the long-term use of the drug, because
the benefits of β-blocker outweigh the side
effects. Most symptoms improve within 2 to
3 months of initial treatment.5,6
Angiotensin II receptor blockers
ARBs inhibit stimulation of the renin-
angiotensin-aldosterone system by blocking
the physiologic effect at the level of an-
giotensin receptors. They do not block
degradation of vasoactive chemicals such as
bradykinin and substance P; they are not
associated with the adverse effects caused
by ACE inhibitors from the accumulation of
bradykinin. ARBs are an acceptable alternative
for treatment of HF patients who cannot toler-
ate ACE inhibitors, and are assigned a class I,
level A of evidence recommendation.5
Initial doses of the drug start out low to pre-
vent hypotension and then increased accord-
ing to the patient’s tolerance levels (Table 1).
Patient’s renal function and blood pressure
need monitoring during treatment to prevent
renal impairment and hypotension. The most
common adverse effect of ARBs is hypoten-
sion, with patients suffering from hypona-
tremia, hypovolemia, renal impairment, and
low baseline blood pressures are more at risk
for developing hypotension. ARBs can worsen
renal function as well as hyperkalemia, and
are contraindicated in pregnancy.5,6
ADJUNCTIVE TREATMENT
Alternative vasodilator therapy
Alternative vasodilation therapy is an
appropriate option for patients with
304 CRITICAL CARE NURSING QUARTERLY/OCTOBER–DECEMBER 2007
contraindications or intolerance to ACE
inhibitors and/or ARBs. The ACC/AHA has
ranked them as a class IIa recommendation,
with a level A of evidence.5 They can be used
in addition to ACE inhibitors when a patient
requires more systemic vasodilation to reduce
preload and after load. This, in turn, improves
cardiac output and hemodynamic parameters
without direct inotropic effect.9 Hydralazine
and isosorbide dimitrate combinations are
the favored drugs for this type of therapy.
Vasodilators are classified by their mechanism
of action; they can be a venodilator, arteriolar
dilator, or a balanced vasodilator. Isosorbide
is a venodilator that redistributes blood from
the venous side of the heart to systemic cir-
culation, which causes a decrease in preload.
Hydralazine is an arteriolar dilator, as it causes
a decrease in afterload. ACE inhibitors and
ARBs are considered balanced vasodilators,
as they exert their effect on both the venous
and arterial sides of the heart.5,6
Diuretics
In HF patients, significant volume overload
should be treated with diuretics in conjunc-
tion with an ACE inhibitor and a β-blocker.
This drug classification is ranked a class I, level
C of evidence and is recommended for pa-
tients with symptoms of fluid retention.4 Di-
uretics promote an increase of sodium and
water excretion by the kidneys. Thiazide-type
diuretics effects occur in the distal tubules of
the kidneys. Loop diuretics work at the loop
of Henle as well as at the proximal and distal
tubules. Diuretics decrease preload by reduc-
ing volume overload.6
Dosages are commonly prescribed at the
lowest fixed dose possible (Table 2). Admin-
istrations of intravenous loop diuretics are
used for patients in the acute care setting
who may require aggressive therapy to con-
trol onset of severe symptoms. Diuretics are
titrated to achieve maximum improvement of
volume overload. Overuse of diuretics should
be avoided before starting ACE inhibitors, as
volume depletion can lead to hypotension and
renal insuffiency.5
Calcium channel blockers
First-generation calcium channel blockers
(CCBs) are not recommended because of their
myocardial depressant effect. Newer vascular
selective dihydrpyridine CCBs, such as am-
lodipine and felodipine, have fewer myocar-
dial depressant effects and are used in ad-
junct to standard HF therapy for treatment of
resistant hypertension and angina.9 Amlodip-
ine and flodipine are prescribed for the treat-
ment of hypertension or angina at a dosage
of 5 to 10 mg daily. The most common side
effects are hypotension, flushing, headaches,
and edema.5,6
Digoxin
The use of digoxin for the treatment of HF
remains controversial, as clinical trials have
not shown a decrease in the mortality rate in
HF patients who were taking digoxin in com-
bination with diuretics and ACE inhibitors.6
However, digoxin is associated with the im-
provement of symptoms when administered
with standard therapy for HF caused by sys-
tolic dysfunction. It has a class IIa, level B
of evidence.5 Digoxin has an inotropic effect
that is caused by inhibiting the cell membrane
sodium-potassium adenosine triphosphatase
activity, which increases calcium entry into
the cell. Calcium has been shown to improve
contractility of myocardium.4
Loading doses of digoxin are not usually
required in the treatment of HF. The dosing
is based on renal function, age, and body
weight, with recommended doses ranging
from 0.125 to 0.25 mg daily. A serum digoxin
level should be drawn approximately 1 to 2
weeks after initial treatment. Once a steady
state is reached, the patient should be mon-
itored periodically for symptoms of toxicity,
including serum electrolytes, serum urea ni-
trogen, creatinine, and serum digoxin level.6
Digoxin toxicity is an adverse effect that
is manifested by central nervous system and
gastrointestinal symptoms. Central nervous
system adverse effects include headaches,
fatigue, malaise, disorientation, confusion,
delirium, seizures, and visual disturbances.6
 Pharmacological Treatment of Heart Failure 305

Table 2. Additional pharmacological treatment for heart failure

Initial Maximum Adverse

dose daily daily dose effects

Aldosterone antagonists
Spironolactone 12.5–25 mg once 25 mg once to Hyperkalemia, gastrointestinal (GI)
twice disturbances, rash
Epherenone 25 mg once 50 mg once Hyperkalemia
Loop diuretics
Bumetanide 0.5–1.0 mg once 10 mg daily, 4–6 h Dehydration, hypokalemia,
or twice hyponatremia, hypomagnesemia,
metabolic alkalosis, hyperuricemia
Furosemide 20–40 mg once or 600 mg, 6–8 h Same as above
twice
Torsemide 10–20 mg once 200 mg, 12–16 h Same as above
Thiazide diuretics
Chlorothiazide 250–500 mg once 1000 mg, 6–12 h Hyperuricemia, hypokalemia,
or twice hypomagnesemia,
hypercholesterolemia
Chlorthalidone 12.5–25 mg once 100 mg, 24–72 h Hyperuricemia, hypokalemia,
hypomagnesemia,
hypercholesterolemia,
hyponatremia, pancreatitis, rashes
Hydrochloroth- 25 mg once or 200 mg, 6–12 h Same as above
iazide twice
Metalazone 2.5 mg once 20mg, 12–24 h Same as above, except less
hypercholesterolemia
Potassium-sparing diuretics
Amiloride 5 mg once 20 mg, 24 h Hyperkalemia, GI disturbances, rash
Spironolactone 12.5–25 mg once 50 mg, 2–3 d Same as above
Triamterene 50–75 mg twice 200 mg, 7–9 h Hyperkalemia, GI disturbances,
nephrolithiasis

Aldosterone antagonists these agents. Baseline creatinine and potas-

Aldosterone antagonists have a class I,
level B of evidence; they should be used care-
fully in selected patient populations.5 These
drugs are classified as aldosterone receptor
blockers. Some HF patients may continue to
have high levels of circulating aldosterone
even if they are on an ACE inhibitor or an ARB.
This is the reason the recommendations sup-
port low dose use of aldosterone antagonists
in patients with moderately severe to severe
symptoms of HF and reduced LVEF. Patients
need monitoring for renal function and potas-
sium concentration during treatment with
sium levels are required prior to initial dos-
ing. Therapy can be initiated if creatinine is
less than or equal to 2.5 mg/dL in men or less
than or equal to 2.0 mg/dL in women and a
potassium level of less than 5.0 mEq/dL.6
CONCLUSION
The ACC/AHA published its first guidelines
for evaluation and management of HF in 1995,
with subsequent revisions in 2001 and 2005.5
These guidelines will continue to be revised
as new evidence emerges from our academic
306 CRITICAL CARE NURSING QUARTERLY/OCTOBER–DECEMBER 2007
centers. Understanding the current guidelines
will provide the knowledge to support their
use in other clinical settings. This will al-
low nursing staff to promote quality patient
outcomes and assist their healthcare institu-
tions and participating healthcare providers
to meet the core indicators set by the IHI and
the ACC/AHA.
REFERENCES
1. American Heart Association. Heart Disease and
Stroke Statistics: 2005 Update. Dallas, TX: American
Heart Association; 2005.
2. Institute of Healthcare Improvement. Improved care
for patients with congestive heart failure. www.ihi.
org/IHI/Programs/Campaign. Accessed January 23,
2007.
3. Francis GS, Tang WH. Pathophysiology of conges-
tive heart failure. Rev Cardiovasc Med. 2003;4(suppl
2):S14–S20.
4. McCance KL, Huether SE. Pathophysiology: The Bio-
logic Basis for Disease in Adults and Children. Salt
Lake City, UT. Mosby; 2002:1030–1034.
5. American Heart Association. Diagnosis and man-
agement of chronic heart failure: 2005 update.
Knowledge of the current recommen-
dations for drug therapy, mechanism of
action, adverse effects, precautions, and
recommended dosing schedule allows nurses
to collaborate with physicians about the
patient’s plan of care, educate patients and
their families, and provide vigilance of the
IHI core standard.
http://circ.ahajournals.org/cgi/conent/full. Accessed
October 08, 2006.
6. Greenberg GH, Hermann DD. Contemporary Diagno-
sis Manag Heart Failure. Newtown, PA: AMM Co Inc;
2002:57–141.
7. Bristow MR. Mechanism of action of beta blocking
agents in heart failure. Am J Cardiol. 1997;80:26–40.
8. Krum H, Sackner-Bernstein JD, Goldsmith RL, et al.
Double-blind, placebo-controlled study of the long-
term efficacy of carvedilol in patients with severe
heart failure. Circulation. 1995;92:1499–1506.
9. Packer M, O’Connor CM, Ghali JK, et al. Effects
of amlodipnine on morbidity and mortality in se-
vere chronic heart failure. N Eng J Med. 327:1107–
1114.