Download MANAGEMENT OF CHRONIC HEART FAILURE

MANAGEMENT OF CHRONIC
HEART FAILURE
(Congestive Cardiac Failure)
1
Heart Failure
• Is a clinical syndrome characterized by
symptoms of breathlessness and/or fatigue,
usually with signs of fluid overload (edema,
crackles heard when listening to the chest).
• The underlying physiological abnormality is a
cardiac output that is inadequate to meet the
metabolic demands of the body, initially during
exercise but, as the syndrome progresses, also
at rest.
2
Heart failure…
• It may be caused by:
-disease of the myocardium itself (most
commonly ischaemic heart disease), or
-by circulatory factors such as volume overload
(e.g. leaky valves, or arteriovenous shunts
caused by congenital defects) or
-pressure overload (e.g. stenosed-i.e.
narrowed-valves, arterial or pulmonary
hypertension).
3
Heart failure…
• Some of these underlying causes are
surgically correctable, and in some either
the underlying disease (e.g.
hyperthyroidism;), or an aggravating factor
such as anaemia or atrial fibrillation, is
treatable with drugs.
4
Heart Failure:Definition
• is an inability of the heart to maintain a
cardiac output sufficient to meet the
requirements of the metabolizing
tissues despite a normal filling
pressure.
5
Aims of treatment:
• Improve quality of life by:
improving symptoms
avoiding side effects
preventing major morbid events such as
myocardial infarction or stroke
delay death
6
Secondary aims of treatment:
• improval cardiac performance
• improve exercise capacity
• reduce arrhythmiasis (ventricular &
supraventricular)
• maintain renal function
• prevent electrolyte disturbance
7
Relevant pathophysiology:
• There is a poor relationship between symptoms
and cardiac performance in chronic heart
failure.
• Treatment that improves cardiac function does
not necessarily improve symptoms or prognosis
and many treatments that have only modest
beneficial effects on cardiac function may have
clear beneficial effects on symptoms and
prognosis.
• In contrast, there may be a relationship
between haemodynamics, symptoms and
prognosis in patients with acute pulmonary
oedema or cardiogenic shock.
8
Cardiac performance is
influenced by:
1)
2)
3)
4)
5)
Preload
Force of Cardiac contraction
Myocardial compliance
After load
Neuro endocrine activation
9
1) Preload:
• This determines ventricular end-diastolic
pressure and volume.
• In normal hearts an increased preload
leads to increased end-diastolic fibre
length, which, in turn, causes increased
force of contraction.
• In heart failure, this response is
reduced or even reversed.
10
2) Force of cardiac contraction:
•
This is determined largely by the intrinsic
strength and integrity of the muscle cells.
Force of contraction is decreased by:
• ischaemic heart disease (myocardial infarction
or chronic severe ischaemia).
• Specific disorders affecting heart muscle e.g.
hypertension and myocarditis.
• Disorders of heart muscle of unknown cause
e.g. idiopathic dilated cardiomyopathy.
11
3) Myocardial compliance:
•
This is an important determinant of
ventricular filling and therefore of CO.
Compliance is decreased by:
• Fibrosis
• Hypertrophy
• Ischaemia
12
4) Afterload:
•
This is the ventricular wall tension
developed during ejection.
Afterload is increased by:
• systemic arterial vasoconstriction
• increased arterial pressure
• obstruction to outflow e.g. aortic stenosis
13
5) Neuro endocrine activation:
•
After an acute cardiac insult plasma
concentrations of renin, angiotension II,
aldosterone, noradrenaline, endothelin, ADH
(arginine vasopressin) and the natriuretic
peptides are increased.
•
If the patient survives and does not require
treatment, then the activity of the reninangiotensin-aldosterone system (RAAS)
return to normal, probably a consequence of
compensatory salt and water retention, but
plasma concentrations of other
neuroendocrine systems remain elevated.
14
5) Neuro endocrine activation:
...
• Once diuretics have been administered,
RAAS activity increases, as do the
concentrations of other neuro-hormones
with the exception of the natriuretic
peptides, which may decline.
• However, as the heart failure progresses,
all the above neuroendocrine system
becomes markedly activated.
15
5) Neuro endocrine activation:
...
• Increased sympathetic activation via
arterial baroreflexes (and possibly a downregulation of inhibitory activity of
baroreceptors leads to sympathetically
mediated increases in renal renin
secretion and further increases in
angiotensin II and aldosterone.
16
5) Neuro endocrine activation:
...
• Neuroendocrine activation may be
responsible for many of the characteristics
features of heart failure. Examples
include:
• Angiotensin II: Vasoconstriction (esp
renal) sodium retention, continuing cardiac
myocyte damage causing progressive
ventricular dilatation (remodelling);
stimulates aldosterone secretion.
17
5) Neuro endocrine activation:
...
• Aldosterone: Sodium retention; potassium loss
and myocardial fibrosis (both may lead to
arrhythmias).
• Sympathetic activation:
 Vasoconstriction, arrhythmias, hypokalaemia
sodium retention. May initially increase cardiac
contractility but has adverse effects on long-term
cardiac function as for angiotensin II by
progressive remodelling following myocardial
damage.
18
5) Neuro endocrine activation:...
• In the mestermined countries heart failure is
caused by one of the following:
ischaemic heart disease
Hypertension
heart muscle disorders
valvular heart disease
19
DRUGS USED TO TREAT HEART
FAILURE
20
Drugs Used to Treat Heart Failure:
1) Diuretics: thiazides, loop diuretics
•
•
2)
•
•
•
•
3)
•
•
4)
•
decrease peripheral and pulmonary oedema
decrease preload by reduction in circulatory volume.
Neuroendocrine antagonists:
ACE inhibitors
β-receptor antagonists
ARBs
Aldosterone antagonists
Drugs with positive inotropic effect;
cardiac glycosides (mainly chronic heart failure)
β-adrenoceptor agonists (acute heart failure only)
Vasodilator agents:
Mainly decrease preload: nitrates (glyceryl trinitrate, isorbide dinitrate and
isosorbide mononitrate).
• Mainly decrease afterload: hydralazine
• Decrease preload and afterload: sodium nitroprusside (acute HF only).
21
Steps In The Treatment Of
Chronic Heart Failure
Reduce workload of the heart
(a) Limit activity level
(b) Reduce weight.
(c) Control hypertension.
22
Steps In The Treatment Of
Chronic Heart Failure…
•
•
•
•
Restrict sodium.
Restrict water (rarely required).
Give diuretics.
Give ACE inhibitors or angiotensin
receptor blockers.
23
Steps In The Treatment Of
Chronic Heart Failure…
• Give digitalis if systolic dysfunction with
third heart sound or atrial fibrillation is
present.
• Give beta blockers to patients with stable
class II -IV heart failure.
• Give vasodilators.
24
SODIUM REMOVAL
• Sodium removal is important step----by dietary
salt restriction or diuretic….especially if
oedema is present.
• In mild failure, it is reasonable to start with a
thiazide diuretic, switching to more powerful
agents as required.
• Sodium loss causes secondary loss of
potassium, which is particularly hazardous
if the patient is to be given digitalis.
25
• Hypokalaemia can be treated with
potassium supplementation or through the
addition of a potassium sparing-diuretic
such as spironolactone
26
ACE INHIBITORS AND ANGIOTENSIN
RECEPTOR BLOCKERS
• In patient with left ventricular dysfunction but no
oedema, ACE inhibitors should be used first.
• Several large studies have compared ACE
inhibitors with other traditional therapies for
chronic heart failure.
• The results show clearly that ACE inhibitors
are superior to both placebo and to
vasodilators and must be considered, along
with diuretics, as first-line therapy for chronic
failure.
27
• However, ACE inhibitors cannot replace
digoxin in patients already receiving
that drug because patients withdrawn
from the cardiac glycoside while on
ACE inhibitors therapy deteriorate.
28
• Additional studies suggest that ACE
inhibitors are also valuable in asymptomatic
patients with ventricular dysfunction.
• By reducing pre-load and after-load, these drugs
appear to slow the rate of ventricular dilatation
and thus delay the onset of clinical heart failure.
• Thus, ACE inhibitors are beneficial in all subsets
of patients, from those who are asymptomatic to
those in severe chronic failure.
29
• It appears that all ACE inhibitors tested to date
have beneficial effects in patients with heart
failure.
• Recent studies have documented beneficial
effects with enalapril, captopril, lisinopril,
quinapril and ramipril..
• The angiotensin II receptors antagonists (e.g.
losartan, valsartan, etc) produce beneficial
hemodynamic effects similar to those of the
ACE inhibitors.
• However, large clinical trials suggest that the
angiotensin receptors blockers should be used
in patients who are intolerant of ACE inhibitors
30
(usually because of cough).
VASODILATORS
• Vasodilators drugs can be divided into
selective arteriolar dilators, venous
dilators, drugs with non-selective
vasodilatory effects.
• For this purpose, the ACE inhibitors may
be considered non-selective arteriolar and
venous dilators.
• The choice of agents should be based on
the patient’s signs and symptoms and
haemodynamic measurements.
31
• Thus, in patients with high filling pressures
in whom the principal symptoms is
dyspnoea, venous dilators such as longacting nitrates will be most helpful in
reducing filling pressure and the symptoms
of pulmonary congestion.
• In patients whom fatigue due to low
ventricular output is primary symptom, an
arteriolar dilator such as hydralazine may be
helpful in increasing forward cardiac output.
32
• In most patients with severe chronic failure
that responds poorly to other therapy, the
problem usually involves both elevated
filling pressures and reduced cardiac
output.
• In these circumstances, dilation of both
arterioles and veins is required.
• In one trial, combined therapy with hydralazine
(arteriolar dilation) and isosorbide dinitrate
(venous dilation) prolonged life more than
placebo in patients already receiving digitalis
and diuretics.
33
BETA-BLOCKERS AND CALCIUM
CHANNEL BLOCKERS
• Many trials have evaluated the potential for
beta-blocker therapy in patients with heart
failure.
• The rationale is based on the hypothesis that
excessive tachycardia and adverse effects of
high catecholamine levels on the heart
failure patients contribute to the downward
course of heart failure patients.
• However, such therapy must be initiated very
cautiously at low doses, since acutely blocking
the supportive effects of catecholamines can
worsen heart failure.
34
• Several months of therapy may be required
before improvement is noted, this is usually
consists of a slight rise in ejection fraction,
slower heart rate, and reduction in symptoms.
As noted above, bisoprolol, carvedilol,
metoprolol have been shown to reduce
mortality.
• The calcium-blocking drugs appear to have
no role in the treatment of patients with heart
failure. Their depressant effects on the heart
may worsen heart failure.
35
DIGITALIS
• Digoxin is indicated in patients with heart
failure and atrial fibrillation.
• It is also most helpful in patients with a
dilated heart and third heart sound.
• It is usually given after ACE inhibitors.
• Only about 50% of patients with normal
sinus rhythm have documented relief of
heart failure from digitalis.
36
• Because it has a moderate but persistent
positive inotropic effect, digitalis can, in theory,
reverse the signs and symptoms of heart
failure. In appropriate patient, digitalis
increases the stroke work and cardiac output.
• The increased output (and possibly a direct
action resetting the sensitivity of
baroceptors) eliminates the stimuli evoking
increased sympathetic outflow, and both
heart rate and vascular tone diminish.
37
• With decreased end-diastolic fiber tension
(the result of increased systolic ejection and
decreased filling pressure), heart size and
oxygen demand decrease.
• Finally, increased renal blood flow improves
glomerular filtration and reduces aldosteronedriven sodium reabsorption.
• Thus, oedema fluid can be excreted, further
reduction ventricular pre-load and danger of
pulmonary oedema.
38
• Digitalis reduces hospitalization and death
from progressive heart failure at the expense
of an increase in sudden death.
• It is important to note that the mortality rate
was reduced in patients with serum digoxin
concentration of 1ng/mL or less but increased
in those with digoxin levels greater than
1.5ng/mL.
39
CLINICAL USE OF DIGOXIN
DIGOXIN
Therapeutic plasma
concentration
0.5- 1.5 ng/mL
Toxic plasma
concentration
> 2ng/mL
Daily dose (slow loading 0.25 (0.125-0.5) mg
or maintenance)
Rapid digitalizing dose
(rarely used)
0.5-0.75 mg every 8
hours for three doses
40
• These values are appropriate for adults
with normal renal and hepatic function.
41
DRUGS WITH POSITIVE
INOTROPIC EFFECTS
• Drugs that inhibit phosphodiesterases, the
family of enzymes that inactivate cAMP
and cGMP, have long been used in the
therapy of heart failure.
• The bipyridines inamrinone and
milrinone are the most successful of
these agents found to date.
42
• Levosimendan, an investigational drug
that appears to inhibit phosphodiesterase
and cause some vasodilatation in addition
to its inotropic effects.
43
BIPYRIDINES
• Inamrinone (previously called amrinone)
and milrinone are bipyridine compounds
that inhibit phosphodiesterase.
• They are active orally as well as
parenterally but only available in
parenteral forms.
• They have elimination half-lives of 3 to 6
hours, with 10 to 40% being excreted in
the urine.
44
PHARMACODYNAMICS
• The bipyridines increase myocardial
contractility by increasing calcium influx in
the heart during the action potential.
• They also have important vasodilating
effect.
• These drugs are relatively selective for
phosphodiesterase isoenzyme 3, a form
found in cardiac and smooth muscle.
45
• Inhibition of this enzyme results in an
increase in cAMP and increase in
contractility and vasodilatation.
• The toxicity of inamrinone includes nausea
and vomiting; arrhythmias,
thrombocytopenia and liver enzyme
changes.
46
• Milrinone appears less likely to cause
bone marrow and liver toxicity than
inamrinone, but it does cause arrhythmias.
• Inamrinone and milrinone are now used
only intravenously and only for acute heart
failure or exacerbation of chronic heart
failure.
47
BETA ADRENOCEPTOR
STIMULANTS
• The selective β1 agonist that has been most
widely used in patients with heart failure is
dobutamine.
• This drug produces an increase in cardiac
output together with a decrease in ventricular
filling pressure
• Some tachycardia and increase in myocardial
oxygen consumption have been reported.
48
• The potential for producing angina or
arrhythmias in patients with coronary
artery disease must be considered, as well
as the tachyphylaxis that accompanies the
use of any β stimulant.
• Dopamine has also been used in acute
heart failure and be particularly helpful if
there is need to raise blood pressure
49
DIURETICS
• Their major mechanism of action in
heart failure is to reduce venous
pressure and ventricular pre-load.
• These reductions have two useful effects:
reduction of oedema and its symptoms
and reduction of cardiac size, which leads
to improved pump efficiency.
50
VASODILATORS
• The vasodilators are effective in acute heart
failure because they provide a reduction in preload (through venodilation), or reduction in after
load (through arterial dilatation), or both.
• Some evidence suggests that long-term use of
hydralazine and isosorbide dinitrate can also
reduce damaging remodeling of the heart.
51
• A synthetic form of endogenous peptide
brain natriuretic peptide (BNP) has recently
been approved for use in acute cardiac
failure as nesiritide.
• This recombinant product increases cGMP in
smooth muscle cells and effectively reduces
venous and arteriolar tone in experimental
preparations. It also causes diuresis.
52
• The peptide has a short half-life of about 18
minutes and is administered as a bolus
intravenous dose followed by continuous
infusion.
• Excessive hypotension is the most common
adverse effect.
53
• Bosentan, an orally active competitive
inhibitor of endothelin, has been shown to
have some benefit in experimental animal
models heart failure, but results in human
trials have not been impressive.
• This drug is approved for use in pulmonary
hypertension. It has significant teratogenic
and hepatotoxic effects.
54
BETA ADRENOCEPTOR
BLOCKERS
• Most patients with chronic heart failure respond
favorably to certain beta-blockers in spite of the
fact that these drugs can precipitate acute
decompensation of cardiac function.
• Studies with bisoprolol, carvedilol, metoprolol
showed a reduction in mortality in patients with
stable severe heart failure but this effect was not
observed with another beta-blocker, bucindolol,
55
• The full understanding of the beneficial
action of beta blockade is lacking, but
suggested mechanism include attenuation
of the adverse effects of high
concentration of catecholamines (including
apoptosis), up-regulation of betareceptors, decrease heart rate, and
reduced remodeling through inhibition of
mitogenic activity of catecholamines.
56
THE END!
• Read on:• The General Principles of Management
of Heart Failure
57
58