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Congestive Heart Failure
Dr Ian Coombes
Adopted from Duncan McRobbie
Principal Clinical Pharmacist (with permission)
Signs and
Symptoms
•
•
•
•
•
•
•
•
fatigue
exertional dyspnoea
orthopnoea
PND
cardiomegaly
pitting oedema
crackles
raised JVP
NYHA
Classification
• NYHA I - no limitation
of physical activity
• NYHA II- slight
limitation
• NYHA III - marked
limitation
• NYHA IV - inability to
carry out physical
activity
Causes
•
•
•
•
•
•
acute MI
hypertension
toxins (alcohol, cytotoxics)
viruses/bacteria
valve disease
cardiomyopathies
Prevalence
•
•
•
•
•
1-2% population
3-5% of those >65 years of age
10% of those >80 years
50% patients die within 2 years of diagnosis
65% of patients with severe CHF die within 1 yr
Survival After Initial Diagnosis of HF
100%
50%
0%
3 months
18 months
Hospitalisations
74,500 hospital admissions in 2000/2001
Length of stay > 13 days (3x average LOS)
1,000,000 in-patient days
Admission rates projected to increase by >50% over the
next 25 years
Readmission rates as high as 50% over 3 months
Readmission - causes
Causes of Readmission
Arrythmias
Infections
Frequency (%)
8-28
16-23
Poor compliance
Angina
Iatrogenic factors
Inadequate drug therapy
15-32
14-33
10
17
Inadequate discharge/follow up
Failed social support system
Erhardt and Cline 1998 (Lancet)
35
21
Signs and Symptoms
Symptoms
SOA
Signs
Tachycardia
Investigations
Chest X-ray
SOBOE
Fatigue
Orthopnoea
PND (Paroxysmal
nocturnal dyspnoea)
Nocturia
Increased JVP
Oedema
Rales
Hepatomegaly
Echocardiogram
Ambulatory ECG
Exercise treadmill
Cardiac catheter
Anorexia
Weight loss
Cardiomegaly
Ascites
Classifying Heart Failure – the New York
Heart Association method
• NYHA I
No symptoms with ordinary physical activity (walking and climbing
stairs)
• NYHA II (mild)
Slight limitation of activity with dyspnoea on moderate to severe activity (climbing
stairs or walking uphill)
• NYHA III (moderate)
Marked limitation of activity. Less than ordinary activity causes dyspnoea
(restricting walking distance and limiting climbing to one flight of stairs)
• NYHA IV (severe)
Severe disability, dyspnoea at rest (unable to carry out physical activity without
discomfort)
Rules of HF
Remember
symptoms
haemodynamics
symptoms
survival
Remember
CO=SVxHR
BP=TPRxCO
Remember
Starling’s Law: preload = force of contraction
Lapace’s Law: large heart = inefficient
Neurohormonal model of Heart Failure –
Sympathetic Response
afterload
cardiac workload
arterioconstriction
norepinephrine
aortic
blood
flow
cardiac output
SNS
Remember
CO = SV x HR
Neurohormonal model of Heart Failure –
renin-angiotensin-aldosterone
afterload
preload
cardiac workload
arterioconstriction
Remember
Starlings
Law
remodelling
Na+ and H2O
retention
aldosterone
cardiac output
Renal
blood flow
RAS
angiotensin
venoconstriction
Treatment of Heart Failure
Remember
Survival = drug treatment
afterload
hydralazine
preload
cardiac workload
diuretics
arterioconstriction
digoxin
norepinephrine
aortic
blood
flow
SNS
Na+ and H2O
retention
spironolactone
aldosterone
cardiac output
Renal
blood flow
RAS
B-blockers
ACE-I
angiotensin
naturetic peptides
NEP-I
nitrates
venoconstriction
Role of Diuretics
• loops most effective
• symptomatic relief
• Na+ retention
•
H2O loss
•
preload ( ventricle
filling pressure)
•
afterload (arterial
dilatation)
Side effects
• dehydration
• hypotension
• hypokalaemia
• hypomagnesaemia
• hypouricaemia and
gout
• non-compliance
issues
Role of ACE-inhibitors
• improves mortality
•
•
•
•
Side effects
(CONSENSUS)
• hypotension (6%)
better than vasodilator
• hyperkalaemia (6%)
therapy (VeHFT I and II)
• cough (40%)
large well conducted
• dizziness (50%)
trials
preload (inhibits effect) • raised serum
creatinine (0.2%)
afterload (inhibits
vasoconstriction)
Circulating Renin-Angiotensin System
angiotensinogen
renin
Ang I
A
C
E
Ang II
AT1/AT2 receptors
Potential Role of Angiotensin (1-7)
angiotensinogen
renin
Ang I
N
E
P
Ang (1-7)
ACE
Ang II
AT1
AT2
ATx
pressor
trophic
antinatriuretic
depressor
antitrophic
natriuretic
depressor
antitrophic
natriuretic
A
C
E
Ang (1-5)
Potential Role of Angiotensin (1-7)
angiotensinogen
ACE
inhibitor
renin
N
E
P
Ang I
ACE
inhibitor
+
Ang (1-7)
ACE
– Ang II
AT1
AT2
ATx
pressor
trophic
antinatriuretic
depressor
antitrophic
natriuretic
depressor
antitrophic
natriuretic
A
C
E
Ang (1-5)
Renin-Angiotensin/Kallikrein-Kinin Systems
kininogen
angiotensinogen
kallikrein
renin
+ bradykinin
Ang I
ACE
kininase II
inhibitor
icatibant
inactive peptides
B2 receptor
B2
knock-out
NO
depressor
antitrophic
cardioprotective
ACE
– Ang II
AT1
AT2
pressor
trophic
antinatriuretic
depressor
antitrophic
natriuretic
Landmark trials with ACE inhibitors in HF
Trial
n
EF%
Drug
Death
Hospitalisation
Follow up
NNT
(death)
CONSENSUS
1987
SOLVD-P
1992
SOLVD – T
1991
ATLAS
1997
253
<35%
(IV)
<35
(I)
< 40
(II-III)
<35
(II-IV)
enalapril
36 vs 50
reduced
1 year
6
enalapril
reduced
4 years
104
enalapril
trend to
reduction
12.3 vs 15.5
reduced
3 years
31
lisinopril
no difference
reduced
4 years
-
4228
2500
3164
Role of ARBs
• improves mortality (ELITE I and II / CHARM)
• added into conventional therapy (ValHeft / CHARM)
• Less s/es
Role of Beta blockers
• improves mortality
(CIBIS 2)
• added into
conventional therapy
• attenuates sympathetic
drive (outweighs -ve ionotropic
effect)
• not all beta-blockers
are equivalent (bisoprolol
and carvedilol best supported by
evidence)
Side effects
• hypotension
• bradycardia
• peripheral
vasoconstriction
• impotence
• bronchospasm
Role of vasodilator therapy
•
preload
(venodilators - nitrates)
•
afterload
(arterial dilators prazosin)
• large trials show good
benefit but lots of side
effects
Side effects
• hypotension
• headache
• tachycardia
• SLE (hydralazine)
Role of Digoxin
• used in initial trials
• myocardial
contractility
• lost favour because of
toxicity
• renally cleared dependent on age,
weight & RF
Side effects
• anorexia
• N,V,D
• abdominal pain
• visual disturbances
• drowsiness
• arrythmias
• heart block
Role of spironolactone
• improves mortality
(RALES)
• added into
conventional therapy
• attenuates aldosterone
effect
• only small doses
required
Side effects
• hyperkalaemia
• gi disturbances
• impotence
• gynocomastia
• rash
Adjunct Therapy
• Digoxin in SR
–
–
–
DIG trial : no mortality benefit but reduction in
hospitalisations and improved symptoms
useful in symptomatic patients where other drug
therapy is optimised
should not be withdrawn from pts with HF
• Anticoagulation
–
–
if prolonged bed rest : prophylactic heparin
if LV dilatation / thrombus : chronic warfarin therapy
Mortality remains high
• ACEi
Risk reduction 35%
(mortality and hospitalizations)
•  Blockers
Risk reduction 38%
(mortality and hospitalizations)
• Oral nitrates and hydralazine
Benefit vs. placebo; inferior to enalapril (mortality)
However: 4-year mortality remains ~40%
Davies
Daviesetetal.al.BMJ
BMJ2000;320:428-431
2000;320:428-431
Gibbs
Gibbsetetal.al.BMJ
BMJ2000;320:495-498
2000;320:495-498
Role of other treatments
• ?? Ca++ channel antagonists - -ve ionotropic, amlodipine
appears safe
• ?? other antiarrythmics • dobutamine - increases CO, but palliative
• Levosimendan- severe CHF
• naturetic peptide inhibitors / recombinant naturetic
peptides- omapatrilat / neseritide
• Biventricular pacing - severe CHF high cost
• transplantation - 85% survival @ 5yrs
Congestive cardiac failure
Pharmaceutical Care Plan
Need for Drug :
Selection of Specific Drug:
Selection of Regimen:
Provision of Drug:
Administration of Drug:
Monitor Effectiveness:
Counsel / Educate:
Evaluate Effectiveness:
Diagnosis of CHF
Symptom control - diuretics
Decrease mortality; ACE, B-blockers
Co-modibdity: anticoagulation
Patient factors
Loading doses, maintenance dose
Drug factors
Timely, accurate
Timing, food
Symptoms, pulse,cholesterol, side effects
Expected effects, side effects
Risks vs benefits
Beneficial effects > detrimental effects??