MANAGEMENT OF PATIENTS WITH HEART FAILURE
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Topic
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Beta-blockers are the new standard for patients with chronic heart
failure
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Article
Foody JM, Farrell MH, Krumholz HM.
Beta-blocker therapy in heart failure: scientific review.
JAMA. 2002;287:883-889.
Background
Despite early perceptions that negative inotropes were harmful to patients
with systolic dysfunction, treatment with beta-blockers has ultimately
proven lifesaving for heart failure patients.
Objective
This review was undertaken to provide a scientific rationale for use of
beta-blockers in patients with heart failure. The article reviewed (1)
results of randomised, controlled clinical trials assessing mortality
benefits of beta-blockers, (2) basic science studies to assess the physiologic
role of beta-blockers, and (3) clinical guidelines for current usage of
beta-blockers in heart failure therapy.
Results
When tested in more than 10,000 patients, beta-blockers (bisoprolol, bucindolol,
carvedilol, and metoprolol) consistently reduced morbidity and mortality
in those with class II through IV heart failure (30% reduction in mortality,
40% reduction in hospitalisations).
In a failing heart, increased adrenergic drive by neurohormones such
as epinephrine serves as a compensatory response that raises cardiac output
and heart rate. However, chronic activation of the adrenergic nervous
system also increases myocardial oxygen demand, ischaemia, and oxidative
stress. The prolonged adrenergic activation likewise contributes to cardiac
remodelling and a dilated cardiac chamber—conditions associated with
deteriorating cardiac function and poor prognosis.
The use of beta-blockers is now strongly supported in guidelines from
the American College of Cardiology and the American Heart Association;
the European Society of Cardiology; and the Heart Failure Society of America.
Conclusion
With emergence of strong evidence that beta-blockers can reduce mortality
and morbidity for patients with heart failure, beta-blocker therapy must
be safely and rationally incorporated into practice to achieve full benefits.
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Article
Farrell MH, Foody JM, Krumholz HM.
Beta-blockers in heart failure: clinical applications.
JAMA. 2002;287:890-897.
Background
Beta-blockers are now clearly recognised to reduce mortality and morbidity
in heart failure patients who have left ventricular systolic dysfunction
and stable fluid status.
Patient cases
This article uses five patient cases to illustrate issues about beta-blocker
usage including patient selection, discussions with patients, management
and monitoring, and office system improvements for delivery of care. Patients
exhibited a wide range of disease and symptom severity. Included are:
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1)
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a 60-year-old man with chronic heart failure (left ventricular
ejection fraction 25%; NYHA II-III) who experiences dyspnoea on
mild-to-moderate exertion and is taking angiotensin converting enzyme
(ACE) inhibitor, digoxin, furosemide, and spironolactone for his
condition;
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2)
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an asymptomatic 62-year-old jogger who is taking aspirin daily
and was measured as having LV ejection fraction of 30% last year—following
an acute myocardial infarction two years ago;
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3)
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an 81-year-old black woman who experiences dyspnoea on minimal
exertion and was recently hospitalised for intravenous diuresis;
this patient has diabetes, chronic obstructive pulmonary disease,
and a pacemaker, and she is on a diuretic and ACE inhibitor;
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4)
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a 34-year-old man with heart failure caused by progressive cardiomyopathy;
he was brought to the emergency department just three days after
a recent hospitalisation; his LV ejection fraction was measured
at 14% and his discharge medications included starting-dose beta-blocker,
furosemide,
ACE inhibitor, and digoxin;
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5)
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A 62-year-old man who is now hospitalised with heart failure; he
had LV ejection fraction of 30%
6 months ago, but has been compliant with medications; he presents
with dyspnoea at rest, orthopnoea, and peripheral pitting oedema
after some dietary indiscretion while on vacation.
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Other topics reviewed
This practical article reviews beta-blocker topics such as selecting patients
for therapy, procedures for initiating therapy, starting and target dosages,
monitoring doses and adverse effects, and developing office systems to
effectively manage heart failure patients.
Conclusion
The successful incorporation of beta-blocker guidelines into practice
requires an understanding of the therapy, as well as development of effective
systems for implementing and monitoring care.
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Topic
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Women and heart failure
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Article
Ghali JK, Pina IL, Gottlieb SS, Deedwania PC.
Metoprolol CR/XL in female patients with heart failure: analysis of the
experience in Metoprolol Extended-Release Randomized Intervention Trial
in Heart Failure (MERIT-HF).
Circulation. 2002;105:1585-1591.
Background
Women and the elderly, two often overlapping populations, are under-represented
in clinical trials; this may result in under-use of potentially beneficial
cardiovascular therapies in these groups. In subgroup analyses for a clinical
trial of the beta-blocker metoprolol in patients with heart failure (MERIT-HF),
women were the only group for whom survival benefit was not shown. It
was not clear whether the failure to show benefit could be attributed
to the female gender or to the limited number of female participants (and
deaths) in the trial. Results of the present analysis clarify this issue
and delineate other beta-blocker benefits in women.
Study design
This study was a post hoc analysis of all women in the MERIT-HF
trial (n=898; NYHA class II-IV; LV ejection fraction < 40%), also evaluating
women with severe heart failure (n=183; NYHA III/IV; LV ejection fraction
< 25%). In addition, the study pooled mortality data for women in related
beta-blocker trials (MERIT-HF; Cardiac Insufficiency Bisoprolol Study,
CIBIS II; and Carvedilol Prospective Randomised Cumulative Survival Study,
COPERNICUS) to test overall survival benefits.
Results
Treatment with metoprolol controlled-release/extended-release (CR/XL)
in women resulted in a 29% reduction in the number of cardiovascular hospitalisations
(p=0.013), and a 42% reduction in hospitalisations for worsening heart
failure (p=0.021). For women with severe heart failure, hospitalisations
were reduced by 57% (p=0.005), and hospitalisations due to worsening heart
failure were reduced by 72% (p=0.004). Pooling of results for mortality
from MERIT-HF, CIBIS-II, and COPERNICUS showed similar survival benefits
in women and men alike.
Conclusion
Benefits of metoprolol CR/XL for patients with chronic heart failure—previously
shown for predominantly male populations—extend to women, including
those women with severe heart failure. Beta-blocker therapy also yields
survival benefits in women with heart failure.
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NEW CONCEPTS IN HEART FAILURE
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Topic
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Current and future drug therapies for congestive heart failure
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Article
Wells G, Little WC.
Current treatment and future directions in heart failure.
Curr Opin Pharmacol. 2002;2: 148-153.
Background
Recent research in the pathophysiology of the failing heart has focused
on deleterious responses of neurohormonal systems, so rational therapies
to blockade such responses (beta-blockers and angiotensin-converting-enzyme
inhibitors) have proven beneficial for patients with chronic heart failure.
Despite these effective therapies, the mortality from heart failure remains
high; current research is investigating other pathological mechanisms
involved in heart failure, as well as new agents that interrupt these
pathways.
Objective of review
This article summarises recently published guidelines for the management
of congestive heart failure, and it also reviews current basic and clinical
research findings for new management approaches.
Conclusions
Hospitalisations and mortality rates remain high for acute and chronic
heart failure, despite abundant clinical trial results to guide therapy.
Over the past 10 years, ACE inhibitors and beta-blockers have emerged
as the cornerstones of treatment of heart failure therapy. In the past
year, study results have extended use of beta-blockers even to patients
with severe heart failure (NYHA IV). It has also become clear that angiotensin
receptor blockers should be reserved for patients unable to tolerate ACE
inhibitors. New classes of drugs—vasopeptidase inhibitors and endothelin
receptor antagonists—are promising. Despite initial excitement over
TNF-a antagonists, studies have been halted because of adverse outcomes.
While most clinical studies have focused on the problem of systolic heart
failure, patients with diastolic dysfunction represent a substantial proportion
of individuals with symptomatic heart failure. Clinical studies that identify
rational treatment for this group of patients are needed in the future.
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Topic
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Groundbreaking new cellular therapies for heart attacks
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Article
Anversa P, Nadal-Ginard B.
Myocyte renewal and ventricular remodeling.
Nature. 2002;415: 240-243.
Background
Continuous renewal of myocardial cells has long been considered impossible.
However, new evidence suggests that multipotent cardiac stem cells may
be able to renew the myocardium, and perhaps even repair the ‘broken
heart’ after myocardial infarction.
Objective of review
The authors concisely review the latest research findings about the
origin and behaviour of cycling myocytes, and discuss how this understanding
can yield clinical advances in myocardial growth and repair. They discuss
new data suggesting that cardiac stem cells do exist and are the source
of tissue renewal. Implanted skeletal myoblasts and bone marrow-derived
cardiomyocytes have not yet been used successfully to reconstitute injured
myocardium. However, new evidence suggests that it may be possible to
tap the growth potential of adult bone marrow cells (BMCs). When injected
locally in the heart, BMCs ‘home to’ infarcted regions; such
cells can then proliferate and differentiate into myocytes, smooth muscle
cells, and endothelial cells, resulting in partial regeneration of the
injured myocardium.
Conclusions
Identification, localisation, and purification of cardiac stem cells are
essential to understanding how the heart remains healthy or progressively
fails. Characterisation of cardiac stem cell biology will ultimately lead
to the discovery of mediators that control cardiac stem cell migration,
proliferation, and differentiation. This understanding could eventually
lead to mending of the ‘broken heart.’
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THE LATEST INFORMATION FOR PATIENTS
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Topic
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Alcohol and heart failure
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Article
Alcohol and risk for heart failure. Summaries for patients.
Ann Intern Med. 2002;136:I-16.
The problem
Heavy and regular alcohol drinking for many years can weaken the muscle
walls of the heart. Weakened muscles stretch and allow the heart to enlarge.
A large, dilated heart cannot pump blood efficiently, and symptoms of
fatigue, shortness of breath, and ankle swelling result. Doctors call
this problem alcohol-related heart failure or alcoholic cardiomyopathy.
On the other hand, it is thought that drinking moderate amounts of alcohol
may actually provide protection against heart failure.
The latest findings
A large, long-term study (2,796 men and 3,493 women followed over six
to 10 years) examined the relationship between different amounts of drinking
and the risk for heart failure. Individuals reported drinking as one to
7 drinks per week, eight to 14 drinks per week, and more than 15 per week.
In men, all levels of drinking were associated with reduced risk of heart
failure, but those who drank moderately (eight to 14 per week) had the
lowest risk. In women, risk for heart failure was not associated with
drinking.
Conclusions
Regular drinking of small, moderate, and heavy amounts of alcohol
for six to 10 years does not increase risk for heart failure. In fact,
drinking may protect men from heart failure. However, because alcohol
affects many organs other than the heart, patients should not base their
decisions about drinking solely on these study results.
The full clinical study report
Walsh CR et al.
Alcohol consumption and risk for congestive heart failure in the Framingham
Heart Study.
Ann Int Med 2002;136: 181-191.
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Topic
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Improving heart function by reducing or quitting drinking
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Article
Drinking less alcohol improves heart function in people with alcohol-related
heart failure. Summaries for patients. Ann Intern Med. 2002;136:
I-20.
The problem
Most doctors believe that patients with alcoholic cardiomyopathy should
avoid all alcohol. Experts have not agreed whether reduced alcohol intake
rather than complete abstinence has any benefits, so further study was
needed.
The latest findings
A new study included 55 men with alcoholic cardiomyopathy. All reported
daily drinking of at least 100 g of alcohol, (i.e., one litre of wine,
10 12-oz. cans of beer, or 10 shots of 80-proof liquor) for at least 10
years. Researchers grouped the men into their level of drinking during
a 4-year study: 1) non-drinkers; 2) moderate drinkers (20-60 g alcohol
daily); 3) heavy drinkers (60-80 g daily); and alcohol abusers (more than
80 g daily). Heart failure worsened in the 16 men who continued to abuse
alcohol (10 died). Heart function improved in the 17 men who stopped drinking
and in the 15 men who drank moderately (none died).
Conclusions
Quitting drinking and reducing drinking to a moderate level are similarly
effective in improving heart function in people with alcoholic cardiomyopathy.
However, physicians should continue to recommend that alcoholic persons
stop drinking entirely, due to their risk for reverting to alcohol abuse.
The full clinical study report
Nicolas JM, et al. The effect of controlled drinking in alcoholic cardiomyopathy.
Ann Int Med. 2002;136:192-200.
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