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Vol. 19 No. 2, June 2004
Tanzania Medical Journal
1
THE CURRENT MANAGEMENT OF CONGESTIVE HEART FAILURE
Eden E Maro
Introduction
Congestive heart failure (CHF) represents a complex
clinical syndrome characterized by abnormalities of left
ventricular function and neurohormonal regulation; which
are accompanied by effort intolerance, fluid retention and
reduced longevity. The four major diagnostic criteria for
this syndrome are: left ventricular dysfunction, exercise
intolerance, pulmonary congestion or oedema and
ventricular arrhythmias.
In 1990, congestive cardiac failure affected 4.7 million
patients in the USA. Annually the condition is newly
diagnosed in 400,000 persons and the total cost of care
exceeds 10 billion US dollars. In Tanzania heart failure
accounted for about 0.3% of all admissions and 2.8% of all
hospital deaths among patients older than 5 years, in the
year 1995.(1)
As the primary and secondary treatment of
hypertension, rheumatic heart diseases and myocardial
infarction improves, the number of patients with CHF will
rise, which will present an increasing medical challenge and
an increasing economic impact.
Cardiac glycosides and diuretics have been considered
standard treatment for patients with CHF for many years.
Within the last decade, however, the use of digitalis has
been debated. Physicians have achieved improved results
by using additional drugs.
Vasodilators, including
angiotensin converting enxyme inhibitors, have been used
with some success, as have B-blockers, phosphodiesterase
inhibitors and other inotropic agents.
The role of
antiarrhythmic agents in treating patients at high risk for
sudden death remains unclear. Anticoagulation clearly has a
role to play in patients with dilated cardiomyopathy as well
as patients with history of thromboembolism.
With our new understanding of neurohormonal
systems and the vascularendothelum, physicians are now
able to derive rational approach to clinical management and
to the development of suitable medications to treat this
chronic disease.
Non-Pharmacologic Therapy
The goals of treatment for patients with CHF are to
make the patient feels better and live longer. Successful
treatment generally requires careful monitoring of salt and
fluid intake and output. Patients should be placed on a lowsodium diet, with the degree of salt restriction depending on
the severity of heart failure. For the majority of patients,
non-added salt diet (2-3g sodium per day) is sufficient.
However stricter salt restriction should be instituted in
patients with refractory symptoms.
Correspondence to: Maro EE, Box 65001, Muhimbili National Hospital , Dar-esSalaam, Tanzania
Dept. of Internal Medicine
Restriction of fluid intake should be increased in those
patients with hyponatraemia or symptoms refractory to
diuretic therapy. The fluid restriction may result in an
uncomfortable sensation of thirst, thus patients should be
advised about measures to quench the thirst such as
lozenges or mints. Exercise training may be beneficial in
CHF and patients should be encouraged to do regular light
aerobic exercise. Patients should be advised to avoid
substances which may exacerbate their condition, including
alcohol and drugs like non-steroidal anti-inflammatory
drugs. Patients as well as family members should be
counselled and educated about CHF, the goal of treatment
and the importance of compliance with diet, fluid restriction
and medications.
Pharmacologic Therapy
It is now well recognized that 10% to 30% of patients
with CHF have normal systolic function, implying that
abnormal left ventricular diastolic function is the main
mechanism responsible for producing congestive symptoms
in these patients. Although heart failure patients with
systolic dysfunction and those with primarily diastolic
dysfunction may show similar symptoms and signs, the
differentiation between the two syndrome has important
therapeutic and prognostic implications. Certainly different
pathophysiologic processes underlie the two syndromes and
compensatory neuroendocrine activation appears to be
largely seen in those patients with systolic dysfunction.
Because the clinical features may fail to distinguish patients
with systolic or diastolic dysfunction, most centres
recommend echocardiography in all patients with suspected
CHF.
Systolic Dysfunction
Systolic dysfunction is characterized by reduced left
ventricular contractility for the degree of preload and
manifest in a reduced left ventricular ejection fraction
(LVEF). As systolic dysfunction is usually associated with
dilatation of the left ventricle and/or prior myocardial
infarction, suggestive clues for the physician include
displacement of the apex, a third heart sounds, enlarged
cardiac shadow on the chest x-ray and Q waves on the ECG.
The agents currently employed in the treatment of
systolic heart failure include: diuretics, ACE inhibitors, Bblockers, and digoxin.
Diuretics
The main action of diuretics is to decrease pre-load.
Although this effect does not improve cardiac output or
survival, diuretics are essential agents for the management
of CHF because they relieve bothersome pulmonary and
peripheral congestion and thus prevent costly
hospitalisation. They are now rarely used as single agents.
Vol. 19 No. 2, June 2004
Tanzania Medical Journal
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The choice between a loop diuretic or a thiazide
depends on the degree of fluid overload and the patients
renal function (thiazides have greatly reduced efficacy in the
setting of renal failure). Patients with refractory fluid
overload despite massive doses of loop diuretics should be
given in addition agents which act on different segments of
the rephron such as thiazides or metolazone which may help
induce a brisk diuresis. Potassium sparing diuretics should
be used cautiously in patients on ACE inhibitors because
ACE inhibitors are known to counteract the depletion of
potassium and magnesium caused by diuretics
similar actions to ACE inhibitors captopril (as measured by
symptoms scores and functional class) but was better
tolerated. Other short term studies have shown survival
benefit with losartan and Irbersatan 3. The valsartan heart
failure trial (val-HeFT) showed that valsartan significantly
reduced the combined end-point of mortality and morbidity
by 13.2% when added to the prescribed therapy of patients
with heart failure. The discussion of whether ACE
inhibitors, angiotensin II antagonists or the combination of
both are superior in the pharmacotherapy of congestive
heart failure is still being investigated.
Ace Inhibitors
Other Vasodilators
ACE inhibitors have become a cornerstone in the
treatment of chronic congestive heart failure as they reduce
morbidity and mortality of these patients. They are the
agents of first choice in the treatment of systolic congestive
heart failure for both symptomatic and asymptomatic
patients. They have been shown to reduce morbidity and
cardiac mortality, decreased hospitalisations and improved
exercise tolerance(2) while in asymptomatic patients with
reduced left ventricular systolic function, hospitalisations
and the progression to overt congestive heart failure were
reduced. Also ACE inhibitors have been shown to reduce
cardiovascular mortality and hospitalisations for congestive
heart failure and acute coronary events (fatal and non-fatal)
in patients with reduced left ventricular function and NYHA
Class II-IV failure or recent myocardial infarction as well as
in post-infarction patients.(2)
The beneficial effects of ACE inhibitors are thought to
be secondary to after-load reduction and amelioration of
neurohormonal activation.(3)
These benefits of ACE
inhibitors appear to be a consistent class effect, thus the
choice of specific agent should be based on the duration of
action and cost. Although the dose required for maximal
therapeutic efficacy is not known, however some studies
support the contention that ACE inhibitor dosage should be
maximised in patients with congestive heart failure (20mg
of enalapril, 150mg of captopril and 10mg of ramipril).
High doses of ACE inhibitors are superior to low doses with
respect to prognosis and symptoms.(3) Euvolaemic or fluid
overloaded patients tend to tolerate ACE inhibitors well,
however those who develop hypotension should have the
dose of their diuretic reduced..
The combination therapy with hydralazine and
isosorbide dinitrate has been shown to improve exercise
tolerance and reduced mortality in patients with moderate to
severe systolic dysfunction (NYHA II-III). The Veteran
Administration Cooperative Study on vasodilator therapy of
heart failure VHeFT-1)(5) studied men with moderately
severe heart failure who were receiving standard therapy.
When hydralazine and isosorbide dinitrate were added to the
therapy, the cumulative mortality at 2 years fell from 34% in
the placebo group to 26% in the treated group, a “mortality
risk reduction” of 25%. To sum up, the combination of
hydralazine with nitrates seems to improve survival.
However, the survival benefits are usually greater with ACE
inhibitors than hydralazine/isosorbide dinitrate combination.
Thus hydralazine/isosorbide dinitrate is now recommended
only for those patients unable to tolerate ACE inhibitors
(due to renal dysfunction, hyperkalaemia, hypersensitivity,
or persistent cough). No evidence that the other direct
vasodilators such as minoxidil and prazosin are of any
benefits in congestive heart failure.
Angiotensin II (A-II) Receptor Antagonists
ACE inhibitors remain first line therapy in patients with
CHF due to systolic dysfunction. However, in patients not
able to tolerate ACE inhibitors induced side effects in
particular cough, angiotensin II antagonists are an
acceptable alternatives. Angiotensin receptor blockers
produce a more complete blockade of the effects of
angiotensin II by a combination of both ACE dependent and
non-ACE dependent pathways but they lack some of the
effects thought to be important to the benefits of ACE
inhibitors such as inhibition of bradykinin degradation(4)
The study of Losartan in the elderly (ELITE) study(4)
confirmed that the angiotensin II antagonist losartan had
Calcium Channel Blockers
The first generation calcium channel blockers
(nifedipine, diltiazem and verapamil) have negative
inotropic effects and they may increase mortality in cardiac
patients.
The Prospective Randomized Amlodipine
Survival Evaluation (PRAISE) trial(6) reported that
amlodipine (a second generation calcium channel blocker)
significantly reduced mortality when added to usual therapy
(including ACE inhibitors) in patients with non-ischaemic
dilated cardiomyopathy and exhibited a neutral effect in
patients with ischaemic disease. Further studies are required
before routine use is recommended.
Beta Blockers
Beta adrenergic receptor blockers have become
established therapy for a broad spectrum of patients with
heart failure due to left ventricular systolic dysfunction, as a
result of the experience from the US Carvedilol Program
and two dedicated survival trials, the Cardiac Insufficiency
Bisoprolol Study II (CIBIS II) and the Metoprolol CR/XL
(controlled
release/extended
release)
Randomized
Intervention Trial on Chronic Heart Failure (MERIT-HF).(7)
In the two survival trials, the beta-blockers, bisoprolol and
Vol. 19 No. 2, June 2004
metoprolol CR/XL, have been shown significantly decrease
mortality by 34%. Speculation about the benefit of betablockers in heart failure has been ongoing for more than two
decades. The results from these recent trials however, have
clearly established their beneficial effects on total mortality,
death due to progressive heart failure and sudden death,
when added to standard therapy with diuretics and ACE
inhibitors. In addition to their effect on mortality, they also
reduce the need for hospitalisation for worsening heart
failure and they are well tolerated.(7) The results of these
trials have changed the attitude about the use of these drugs.
Nevertheless resistance to their incorporation into clinical
care continues largely due to concerns about their benefit in
patients with severe heart failure. The recent Carvedilol
Prospective
Randomized
Cumulative
Suvival
(COPERNICUS) trial showed a 35% decrease in mortality
(95% confidence interval (CI), 19% to 48%, p=0.00014) in
a patient population with a mean baseline ejection fraction
of 0.20 i.e. severe heart failure.(8)
On the basis of several trials, beta-blocker treatment has
been included in the current guidelines for CHF therapy and
is now strongly recommended as standard therapy for all
patients with CHF and systolic dysfunction. Beta-blocker
treatment should be initiated in stabilized patients with no
pulmonary oedema, hypoperfusion, hypotension or the other
contraindications of B-Blockers. The doses should be
carefully uptitrated to the target dose or the highest tolerated
dose.
Digoxin
Digoxin is a positive inotrope which reduces
neurohormonal activation and inhibits AV nodal
conduction. It is strongly recommended in patients with
systolic dysfunction and atrial fibrillation, however its role
in heart failure with sinus rhythm was once debatable.
Studies have shown addition of digoxin to the treatment
regiment of patients with systolic dysfunction significantly
reduced deaths and hospsitalisations due to worsening heart
failure, however there was no change in overall mortality.
Patients with lower ejection fractions, dilated hearts, severe
symptoms (NYHA II-IV) and non-ischaemic aetiologies
benefited most from digoxin. Based on the available
evidence digoxin has a role as a fourth line agent for
symptom relief in those patients with sinus rhythm and
systolic heart failure refractory to ACE inhibitors Bblockers and diuretics.
Other Inotropes
Studies on inotropic agents other than digoxin have not
been encouraging. Intravenous dobutamine and dopamine
do improve the short-term hemodynamic profile in patients
with systolic congestive heart failure but do not improve
long-term survival. Thus they have a role in the critical care
areas only.
Natriuretic Peptides
Tanzania Medical Journal
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Despite the first line use of ACE inhibitors, and more
recently beta-adrenergic blocking agents, the prognosis of
CHF remains poor. The Natriuretic peptides are counter
regulatory to the rennin angiotension system, causing
vasodilatation; diuresis and natriuresis. Augmention of their
levels with exogenously administered atrial natriuretic
peptide (ANP) and brain natriuretic peptide (BNP) resulted
in a reduction in filling pressures, natriuresis and deuresis in
acute studies on CHF.
However, their therapeutic
usefulness is limited by a short half-life, due to rapid
degradation by neutral endopeptidase (NEP). Omapatrilat is
the first of a new class of drugs known as vasopeptidase
inhibitors which simultaneously inhibit both neutral
endopeptidase (NEP) and angiotension converting emyme,
resulting in increased levels of natriuretic peptides and
bradykinin with a reduction in angiotension II. In patients
with heart failure, omapatrilat therapy for 24 weeks showed
a similar increase in week 12, exercise tolerance but
conferred more benefit than lisinopril in the composite of
death, hospital admission or discontinuation of study
treatment for worsening heart failure.(9)
Although
promising, more trials are required.
Anti-Arrhythmic Therapy
In patients with symptomatic or life threatening
arrhythmias (sustained ventricular tachycardia or ventricular
fibrillation), the type III anti-arrhythmic drugs amiodarone
and perhaps sotalol, are the agents of first choice. In the
GESICA trial addition of amiodarone to standard therapy in
patients with systolic congestive heart failure was associated
with a statistically significant reduction in mortality.
Currently amiodarone is recommended for routine use in
congestive heart failure patients with symptomatic
arrthymias. On the other hand sotalol was shown to cause
excess mortality and thus it has no place in patients with
compromised left ventricular function. Despite the progress
in therapy for congestive heart failure at least 40% of
patients die suddenly, mainly as a result of ventricular
tachyarrhythmias.
Anticoagulation
Warfarin prophylaxis is recommended for most patients
with coexistent congestive heart failure and atrial
fibrillation. Also in the absence of clear contraindications,
Warfarin anticonagulation (with a goal PT.INR of 2-3) is
recommended for patients who have a history of
thromboembolism, episodes of atrial fibrillation, dilated
poorly functioning left ventricle (ejection fraction < 25%)
with
evidence
of
intracardiac
thrombus
on
echocardiography.
Diastolic Dysfunction
The main defect in patients with diastolic dysfunction is
impaired ventricular relaxation and decreased compliance in
diastole. Thus, these patients with diastolic dysfunction,
usually have normal left ventricular ejection fraction, but
increased left atrial pressures and chamber pressures
Vol. 19 No. 2, June 2004
increases markedly in response to increases in left
ventricular volume. The common causes of left ventricular
diastolic dysfuntion are: hypertension, mitral stenosis, aortic
stenosis,
hypertrophic
obstructive
cardiomyopathy,
restrictive cardiomyopathy and myocardial ischaemia and/or
infarction. These conditions which are associated with
diastolic dysfunction, usually do not lead to significant
cardiac enlargement and the only clues may be a normal
heart size on chest x-ray and the presence of left ventricular
hypertrophy on physical examination (sustained apex heave,
fourth heart sound) or ECG.
The central goals to the treatment of diastolic
dysfunction is to improve the compliance of the left
ventricle and increase diastolic filling. Slowing of the heart
rate (and therefore increasing diastolic filling time) and
treating myocardial ischaemia with beta-blockers or calcium
channel antagonists is indicated where appropriate. Studies
have shown that the non-dihydtropyridine calcium channel
blockers (verapamil and diltiazem) given to patients with
congestive heart failure with diastolic dysfunction,
improved clinical status, exercise capacity and diastolic
filling by altering the calcium flux in the myocardium.
Reduction of mortality or hospitalisation was not reported.
Diuretics are recommended for symptomatic treatment,
however with caution so as not to excessively reduce
preload.
In patients with constrictive pericarditis, cardiac
tamponade, mitral stenosis and restrictive cardiomyopathy,
ACE inhibitors are contraindicated.(10) The notion that ACE
inhibitors are useful in patients with mainly diastolic
dysfunction requires proof in well executed studies.
Conclusion
In patients with congestive heart failure, the distinct
syndrome of systolic dysfunction and diastolic dysfunction
do determine the therapy. Results from previous studies
supported the concept that triple therapy with diuretic, ACE
inhibitors and digoxin was the most effective treatment
strategy in symptomatic heart failure due to systolic
dysfunction. However recent trials showed that adding
beta-blockers (carvedilol, metoprolol and bisoprolol) to
ACE inhibitors do significantly reduce the morbidity,
mortality, progression of heart failure and the recurrent
hospitalisation
risk
(and
accompanying
costs).
Angiotension II antagonists are acceptable alternatives in
those patients unable to tolerate ACE inhibitor side effects.
Amiodarone appears to be safe for symptomatic arrhythmias
in heart failure.
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