• Approximately 5 million American adults are

affected by chronic heart failure (CHF), with

550,000 new cases occurring each year.

• Prevalence approaches 10% of the population

older than age 75.

• CHF is the most common cause for

hospitalization within the Medicare population.

• After hospitalization for CHF, 40% of the

patients are readmitted within 3 months.

• Annual health care costs exceed $24 billion,

with the majority spent on hospitalizations.

• Within the VA health care system, in 2001

there were more than 311,000 veteran patients

with a diagnosis of CHF, and more than

110,000 hospitalizations.

• In FY 2002, VA costs for CHF care were

estimated at $2.4 billion.

PRACTICE PRACTICE Matters Matters

February, 2004 VOL. 9 ISSUE 1

A publication of the Management Decision and Research Center

A program within the Department of Veterans Affairs Health Services Research and Development Service

TREATING

CHRONIC

HEART

FAILURE
2 PRACTICEMatters

BACKGROUND

Chronic heart failure (CHF) is a highly

prevalent and costly disease, especially in the elderly

– 1 in every 10 elderly persons has this condition.1

Almost one-half of CHF patients are readmitted to

the hospital within six months of discharge, and

approximately two-thirds of veterans with CHF die

within five years of their initial hospitalization.

Hospital and health care resource use associated

with CHF is high, with heavy utilization of both

inpatient and outpatient services.

While CHF can be cured only rarely, the goal is

to maintain the quality of life and independent

living, and to improve life expectancy. Approaches

to the CHF patient should include disease

counseling and education, dietary and exercise

recommendations, and a wide range of

pharmacological treatment options. 

Diagnosis

Common presentations of patients with CHF

include: shortness of breath, decreased exercise

tolerance, fatigue, and fluid retention. However,

many patients have asymptomatic left ventricular

dysfunction (LVD) and are diagnosed only

incidentally.

Initial evaluation in patients suspected of having

heart failure should include an in-depth history and

physical exam. A detailed history is critical for

determining the precipitating factor(s) leading to

decompensation (e.g., medication or dietary nonadherence, use of concomitant medications, etc.).

The physical exam should focus on the assessment

of fluid status, including serial weights, evaluation of

jugular venous pressure (JVP), checking for

peripheral edema, and listening to the lungs and

heart for the presence of rales and an S3 gallop,

respectively, as well as cardiac murmurs that might

indicate valvular abnormalities. Physical findings

help not only in diagnosis, but may also aid in

prognosis.2

A two dimensional echocardiogram, using

Doppler flow studies, is useful in determining the

presence of structural disease while assessing the

extent of LVD, and potentially delineating the

etiology, such as valvular disease or coronary artery

disease (CAD). It should be emphasized, however,

that an echocardiogram is predominantly useful for

assessing left ventricular function that can add to the

probability of a patient’s symptoms being attributed

to heart failure, but LVD and normal left ventricular

function can both be present with and without

symptoms of heart failure. Thus, the diagnosis of

CHF remains a clinical entity based on symptoms

and the physical exam.

The New York Heart Association (NYHA)

functional classification system has withstood the test

of time as a simple but effective system to provide

important prognostic information and to aid the

clinician in determining appropriate therapy.

According to the NYHA system, Class I patients are

those with impaired LV function, but who have no

limitation with ordinary physical activity. Class II

patients have slight limitation of physical activity.

Those with Class III symptoms are comfortable at

rest but have symptoms with less than ordinary

activity, and Class IV patients are unable to

participate in any physical activity without symptoms.

In addition, a blood test for B-type natriuretic

peptide (BNP) is emerging as an important marker

for diagnosis of heart failure in some patients and

clinical settings. The sensitivity and specificity are

both > 90%.3 Further, BNP correlates with the

extent and prognosis of CHF. 

CHF CLASSIFICATIONS 

AND TREATMENT

The importance of patient self-management

cannot be overstated. Appropriate dietary

counseling should be given with particular emphasis

on sodium restriction. Patients should be advised to

follow a moderate exercise regimen, consisting of

walking for at least 20-30 minutes for a minimum of

three times per week, and advanced as tolerated.

Daily weight measurement can aid in detecting early

signs of fluid accumulation and may guide in flexible

diuretic dosing. Finally, the importance of

maximizing adherence to medical therapy to avoid

hospitalization should be emphasized.

The new classification for CHF underscores the

progressive nature of the disease, and emphasizes

opportunities for early intervention and prevention.

This new approach to CHF has been incorporated

in guidelines published jointly by the American

College of Cardiology and the American Heart

Association.6 Four stages of heart failure have been

defined – Stages A through D. 
Stage A

Patients at this (“pre-CHF”) stage have risk

factors associated with the development of CHF but

do not have any identifiable structural or functional

cardiac abnormalities. The goal of treatment for

stage A patients is the prevention of structural

changes in the heart by identifying and aggressively

treating patients at risk of developing overt heart

failure. This includes treating hypertension, CAD,

and diabetes. Studies have demonstrated that the

incidence of CHF can be reduced by half with

effective treatment of hypertension.

7 Other

recommendations include the treatment of lipid

disorders, and avoidance of habits that may increase

the risk of CHF such as – smoking, excessive

alcohol consumption, and illicit drug use. 

Angiotensin converting enzyme (ACE)

inhibitors decrease morbidity and mortality in

patients with a history of atherosclerotic vascular

disease, diabetes mellitus, or hypertension and

associated cardiovascular risk factors. 

Stage B

Patients who demonstrate LVD in the absence

of symptoms are considered to be in Stage B

(NYHA Class I), which also includes patients with a

history of myocardial infarction. Such patients are

at high risk of developing symptomatic CHF. The

goal of therapy in Stage B is to reduce the risk of

additional injury and to prevent the progression of

LVD.

ACE inhibitors are considered the standard of

care in patients with LVD, whether or not they have

experienced a myocardial infarction, and in patients

with or without LVD who have a recent or remote

history of myocardial infarction. Use of ACE

inhibitors in this stage of CHF reduces the

frequency of hospitalization.8 Beta-blockers, which

are used for angina, arrhythmias, and hypertension,

also reduce mortality in patients with a history of

myocardial infarction. Valve replacement or repair

for patients who have significant valvular disease is

also highly recommended.6

Stage C

Stage C patients have LVD and current or

previous symptoms (NYHA Class II-III). These

patients should be treated with all therapies listed in

Stage A and B, including ACE inhibitors, betablockers, and treatment of risk factors. In the

Studies of Left Ventricular Dysfunction (SOLVD)

and other similar trials with symptomatic CHF,

ACE inhibitors conferred a 20-25% reduction in

mortality.8 Three large beta-blocker trials, enrolling

approximately 10,000 patients with CHF, showed a

35% survival benefit in patients with CHF Stages C

and D.9-11 Close follow-up is needed to guide

specific therapy, such as the use of diuretic

medications in patients with signs of fluid retention. 

While digitalis does not increase survival rates, it

does lead to improvement in symptoms and a

reduction in hospitalization, and continues to be

useful, especially in more symptomatic CHF

patients. Spironolactone is recommended for

patients with advanced symptoms, preserved renal

function, and normal potassium. 

Exercise training and angiotensin receptor

blockers (ARB’s) may be helpful for patients in Stage

C who do not tolerate ACE inhibitors, but this has

not been proven unequivocally.6, 12-14

Stage D

These patients have advanced structural heart

disease and remain symptomatic at rest, despite

optimal medical therapy (NYHA Class IV). All

recommendations for heart failure therapy for

previous stages also apply to Stage D. Patients

developing end-stage and refractory heart failure

should have careful follow-up, with particular

PRACTICEMatters 3

VA Practice Matters is a publication for VA decision makers

and practitioners that summarizes the results of important

research to help inform policy and to promote the

application of research for improved health care delivery and

decision making within VA. It is produced by HSR&D’s

Information Dissemination Program in collaboration with

topic experts in the field. For more information or to

provide us with your suggestions, please contact:

Information Dissemination Program

VA Boston Health Care System

150 South Huntington Avenue

Boston, MA 02130

Phone: (617) 278-4433 

FAX: (617) 278-4438

Email: geraldine.mcglynn@med.va.gov

VA Practice Matters is also available on the 

VA HSR&D internet at

www.hsrd.reasearch.va.gov/publications/practice_matters/
4 PRACTICEMatters

attention to the management of fluid retention.

Referral to a heart failure program with expertise in

the management of refractory heart failure can also

help patients at this stage. All efforts should be

attempted to correct reversible causes of heart

failure, such as revascularization in patients with

signs of ischemia, or performing valvular repair or

replacement. Referral for cardiac transplantation

and implantation of devices in eligible patients

should be made (see below). 

Improving Treatment

Despite substantial evidence of excellent

pharmacologic benefit to prevent and treat heart

failure, as well as agents that reduce mortality in

patients with symptoms, the under-utilization of

appropriate therapy remains surprisingly large.

Surveys show ACE inhibitors are used in only

slightly more than 50% of patients, and betablockers in only about 35% of patients. Thus, there

is a great need for: 

• improved education, 

• easier access and referral to specialists, and 

• establishment of specialized heart failure

programs. 

When patients are treated under these programs,

studies show marked improvement in the use of

appropriate medications, quality of life, and survival. 

While ACE inhibitors and beta blockers have

emerged as standards of care for patients with

CHF due to potent effects on mortality,

hospitalizations, and symptoms, studies suggest

that these agents are still widely under-utilized.

However, mortality for CHF patients remains over

7-8% annually even with optimal treatment, so

studies to evaluate newer approaches for treating

CHF are needed and continue.

New Drug Therapies

Angiotensin Receptor Blockade

While ACE inhibitors block the conversion of

angiotensin I to angiotensin II, other “ACEindependent” pathways can still lead to the

production of angiotensin II. Angiotensin-receptor

blockers (ARBs) block the actions of angiotensin II

at the level of the receptor, regardless of the path by

which angiotensin II is produced. The Evaluation

of Losartan in the Elderly (ELITE-II) Trial

compared the effects of an ACE inhibitor (enalapril)

with an ARB (losartan), and the ACE inhibitor was

marginally superior to the ARB in this study.1,5 

Val-HeFT

A slightly different approach was taken in the

Valsartan in CHF Trial (Val-HeFT), in which 5,010

patients with CHF were randomized to

conventional therapy (ACE inhibitor, digoxin,

diuretics), or conventional therapy plus the ARB

valsartan.16 While valsartan did not alter mortality,

the risk of hospitalization for CHF was decreased

compared to placebo. The benefits were not seen in

patients also taking a beta-blocker. In the small

group of patients not taking ACE inhibitors,

valsartan decreased mortality.

CHARM

The Candesartan in Heart Failure Assessment

of Reduction in Mortality and Morbidity (CHARM)

study examined the use of the ARB candesartan in

7,601 patients with CHF. This study had three

distinct “arms.” CHARM-Alternative, which

enrolled patients intolerant to ACE inhibitors,

confirmed findings from Val-HeFT that ARB’s

reduce morbidity and mortality in patients

intolerant to ACE inhibitors, with good tolerability.

CHARM “Added” examined the use of candesartan

in patients already taking an ACE inhibitor and, in

contrast to Val-HeFT, found that the ARB further

reduced morbidity and mortality. The “Preserved”

arm studied patients with CHF with ejection

fractions (EF) > 40%, and found no reduction in

mortality, but a beneficial effect of the ARB on CHF

hospitalization of borderline statistical significance.

Current guidelines recommend ARBs in patients

who cannot tolerate ACE inhibitors, but the

CHARM results suggested added benefits of

candesartan in CHF patients whether or not they

were taking either ACE inhibitors or beta-blockers,

regardless of EF.

Aldosterone Inhibition 

One of the mechanisms for the toxic effects of

sustained renin angiotensin aldosterone system

activation is through the increased production of
aldosterone. Elevated aldosterone levels have

several adverse consequences in patients with

CHF.17, 18 Given this background, aldosterone

antagonists have been evaluated in CHF patients. 

RALES

In the Randomized Aldactone Evaluation Study

(RALES) 1,663 patients with current or recent

advanced CHF were randomized to receive

conventional therapy (ACE inhibitors, loop

diuretics, digoxin and in some cases beta-blockers),

or conventional therapy plus low dose

spironolactone, an aldosterone antagonist. Low

dose spironolactone was associated with a 30%

reduction in the risk of death and a 35% reduction

in hospitalization for worsening CHF compared to

placebo. Because spironolactone use may lead to

hyperkalemia, it is not recommended in patients

with hyperkalemia or significant renal insufficiency.

After beginning at a dose of 12.5 - 25 mg daily,

serum potassium should be checked at one week and

at one month after the initiation of therapy. This is

recommended in patients with current or recent

NYHA Class IV patients.

EPHESUS

Spironolactone often has unwanted

progestational and antiandrogenic side effects that

may limit its chronic use. Newer mineralocorticoid

receptor antagonists (e.g., eplerenone) have been

developed for more selective aldosterone

antagonism resulting in a much lower incidence of

the sex hormone related side effects.19,20 The

recently completed Eplerenone Post-AMI CHF

Efficacy and Survival Study (EPHESUS) compared

the effect of eplerenone (25-50 mg daily) plus

standard therapy to placebo plus standard therapy

(including ACEIs and beta-blockers) in 6,632

patients with recent acute myocardial infarction,

depressed left ventricular systolic function, and CHF

or diabetes.21 Eplerenone reduced mortality by 15%.

Thus the role of aldosterone antagonists has

been established in patients with advanced CHF, as

well as in post myocardial infarction patients with

left ventricular systolic dysfunction. No data are

available currently that demonstrates benefit of these

agents in patients with moderately severe CHF.

PRACTICEMatters

Alternatives to Pharmacologic Approaches

Even good pharmacotherapy for patients with

CHF does not normalize life expectancy, and

significant numbers of patients continue to have

sub-optimal quality of life. Therefore, alternatives

to pharmacologic approaches have been tested over

the past few years.

Implantable Cardiodefibrillators (ICD’s)

Between 40-60% of patients with CHF die

suddenly, most often from tachyarrhythmias

(disturbance in heart rhythm resulting in rapid heart

beat). While beta-blockers reduce mortality from

sudden death, they do not eliminate the risk entirely.

Multicenter Automatic Defibrillator Implantation

Trial II (MADIT-II)22 studied the effect of

implantable cardiodefibrillators (ICD’s) on the

primary prevention of mortality in 1,232 patients

with a prior myocardial infarction and a left

ventricular ejection fraction of <30% ( 70% of the

patients were receiving an ACE inhibitor, BB, or

both). The ICD group showed a 31% reduction in

all-cause mortality compared to controls. While the

investigators stated that the effect was consistent

regardless of the QRS interval, the data suggested

that the effect was greatest in those patients with the

widest QRS intervals, leading the Centers for

Medicare and Medicaid Services (CMS) to approve

coverage for ICDs in patients meeting this more

stringent criteria, i.e., QRS > 120msec.

Representatives from major cardiology

organizations have hotly contested this decision. 

Biventricular Pacing in CHF (BiV)

Patients with advanced CHF often have enlarged

hearts, slowed electrical activation, and ventricles 

that do not contract in a synchronized manner.

Approximately 30% have intra-ventricular

conduction defects of varying severity.

Biventricular pacing (BiV), or resynchronization

therapy, attempts to improve the pattern of LV

activation, normalize the delay between atrial and

ventricular systole, and improve mechanical

efficiency of the failing heart.

Small, short-term trials targeted advanced CHF

Continued on page 7

5
6 PRACTICEMatters

CLINICAL OPINION

Over the past two decades, remarkable

advances have occurred in the management of

chronic heart failure (CHF). Several warrant

highlighting.

• 1983: First multi-center controlled trial

demonstrating efficacy of an ACE inhibitor 

• 1986: V-HeFT—first demonstration of

improved survival in CHF

• 1987: CONSENSUS—first demonstration of

survival benefit from ACE inhibitor, 

• 1995: First large controlled trial of a heart

failure management program published

• 1996: First multi-center trial demonstrating

improved survival with beta-blockers, 

• 1999: RALES—first demonstration of survival

benefit with aldosterone blockade

• 2001-2003: Evolving evidence of reduced

morbidity and mortality with devices (cardiac

resynchronization, left ventricular assist

devices, and implantable cardiodefibrillators)

Outcomes of CHF patients are improving.

Annual mortality rates of mild to moderate CHF

patients in trials have declined from 15-20% to

7%. Improvements are also apparent in

epidemiological and cohort studies. However, this

is not a time for complacency. As statistics

illustrate, mortality, morbidity, and health care

resource utilization remain unacceptably high. I

would like to emphasize three specific challenges

that must be addressed successfully if we are to

reduce the burden of CHF.

First, the discrepancies between what can be

achieved and what occurs in practice must be reduced.

This is the goal of VA’s Quality Enhancement

Research Initiative (QUERI). QUERI’s mission is

to facilitate the systematic implementation of

clinical research findings and evidence-based

recommendations into routine clinical practice.

Thus for CHF-QUERI – one of eight conditionspecific QUERI groups – the first step is to ensure

that all appropriate patients receive ACE

inhibitors, beta-blockers, and aldosterone

antagonists, as well as appropriate management of

volume status. While provider education remains

a cornerstone of changing practice, it is clearly not

sufficient. Promising approaches include greater

Continued on page 7

KEY RECOMMENDATIONS

• Treatment for CHF should include disease

counseling and education, dietary and exercise

recommendations, and a wide range of

pharmacological treatment options.

• CHF patients should be administered

angiotensin converting enzyme (ACE) inhibitors

at appropriate doses.

• Patients intolerant of ACE inhibitors should

receive an angiotensin receptor blocker (ARB).

• CHF patients should be prescribed a betablocker, shown in clinical trials to be effective at

appropriate doses 

• Patients with advanced CHF, and those with HF

following a myocardial infarction (MI) should

receive an aldosterone antagonist.

• ARB’s should be strongly considered for patients

who remain symptomatic or who have been

hospitalized.

• Bi-ventricular pacing should be reserved for

those patients with LBBB who remain

symptomatic despite optimal medical therapy. 

• Implantable cardiodefibrillators (ICDs) should be

strongly considered in patients with a history of

MI and low ejection fraction.

ACKNOWLEDGEMENTS 

This issue of VA Practice Matters on Treating

Chronic Heart Failure was written by Mark Dunlap,

MD, Clinical Coordinator for the Chronic Heart

Failure Quality Enhancement Research Initiative

(CHF QUERI); Rebecca Beyth, MD, Research

Coordinator for CHF QUERI; Anita Deswal, MD,

Member of the CHF QUERI Executive Committee

and Cardiologist at the VAMC in Houston, TX;

Barbara Kimmel, MS, MSc, Administrative

Coordinator and Acting Implementation Research

Coordinator for CHF QUERI; Barry Massie, MD,

Director of the Coronary Care Unit and Director of

the Heart Failure and Hypertension Unit at the

VAMC in San Francisco, CA; and Jahandar Saleh,

MD, Research Fellow in the Department of

Cardiology at UCLA/VA Greater Los Angeles Health

Care System. Robert L. Jesse, MD, National

Program Director for Cardiology, Richmond, VAMC,

and John G. Demakis, MD, Director of HSR&D,

reviewed the issue and provided comments. This

issue was edited by Geraldine McGlynn, MEd, and

Diane Hanks, MA, with HSR&D’s Information

Dissemination Program.
PRACTICEMatters 7

Continued from page 5

patients with EF of <20% and LBBB (left bundle

branch block). These trials mostly showed

improvements in the magnitude and synchrony of

contraction. In the Multicenter InSync

Randomized Clinical Evaluation (MIRACLE) trial,

more than 400 patients were randomized to either

BiV pacing or placebo pacing (i.e. implant with no

pacing).23 Patients with moderate to severe CHF

were enrolled with EF < 35%, QRS duration > 130

msec, and on medical therapy optimized by the

investigator. More than 90% of patients were

receiving an ACE inhibitor, though < 60% were

taking beta-blockers. The BiV group showed

improvements in exercise tolerance, quality of life,

and degree of CHF, as well as reductions in

hospitalizations and length of stay at six months.

Based primarily on these data, the FDA has

recently approved BiV for adjunctive treatment of

patients with moderate to severe CHF, who, in

spite of medical therapy, remain symptomatic and

have dysynchrony. 

The recently completed Comparison of

Medical Therapy, Pacing and Defibillation in Heart

Failure (COMPANION) trial studied the use of

BiV compared to combined BiV and ICD to

optimal medical therapy in patients with moderate

to severe CHF (EF < 35%, and QRS interval of >

120 ms).24 In this non-blinded trial, the results

pointed to a mortality benefit in the combined BiV

and ICD group, with a reduction in hospitalizations

from BiV alone.

Devices—summary

Since not all patients with current criteria for

BiV improve following implantation of the device,

an important dilemma is identifying patients who

would benefit the most from BiV, in addition to

aggressive medical therapy with ACE inhibitors and

beta-blockers. Additionally, complications,

sometimes serious, can occur with the specialized

lead placement required. At this time, selection

criteria for these patients needs to be better defined.

Referral to a Cardiologist is indicated for patients

who might be candidates, including CHF with

continued Class III or IV symptoms, especially in

patients with a wide QRS complex. ICD’s are

indicated in CHF patients with a high risk of sudden

death, including ischemic cardiomyopathy and EF <

35%, especially with a wide QRS complex. These

indications may change with publication of new

studies, some of which are anticipated this year.

Clinical Opinion Continued from page 6

involvement of specialists even at early stages of the

process, use of multidisciplinary interventions, and

facilitating patient self-care.

Second, in the face of an increasing number of

potentially effective interventions (e.g. new

medications, devices, etc.) we must determine

which ones offer optimal management in which

potential candidates, and at what cost and benefit.

And third, we must address a glaring gap in our

knowledge. For example, approximately 40% of

CHF patients who have preserved systolic function,

which includes the majority of women and those

over age 75, there are no proven effective therapies. 

Great strides have been made in the

management of heart failure. Now is the moment

to address the difficult challenge of translating

these advances into better care and outcomes for

our patients.

Barry Massie, MD

Director, Coronary Care Unit, and Heart

Failure and Hypertension Unit 

VAMC, San Francisco, CA 

REFERENCES:

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Update, American Heart Association. Dallas, Tex. 2003. 

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8 PRACTICEMatters

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