Congestive Heart Failure Dr Ian Coombes Adopted from Duncan McRobbie Principal Clinical Pharmacist (with permission)
Dec 22, 2015
Congestive Heart Failure
Dr Ian CoombesAdopted from Duncan McRobbie
Principal Clinical Pharmacist (with permission)
Signs and Symptoms
• fatigue• exertional dyspnoea• orthopnoea• PND• cardiomegaly• pitting oedema• crackles • raised JVP
• NYHA I - no limitation of physical activity
• NYHA II- slight limitation
• NYHA III - marked limitation
• NYHA IV - inability to carry out physical activity
NYHA Classification
• acute MI• hypertension• toxins (alcohol, cytotoxics)• viruses/bacteria• valve disease• cardiomyopathies
Causes
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
Hospitalisations
74,500 hospital admissions in 2000/2001Length of stay > 13 days (3x average LOS)1,000,000 in-patient daysAdmission rates projected to increase by >50% over the
next 25 yearsReadmission rates as high as 50% over 3 months
Readmission - causesCauses of Readmission Frequency (%)
Arrythmias 8-28Infections 16-23Poor compliance 15-32Angina 14-33Iatrogenic factors 10Inadequate drug therapy 17Inadequate discharge/follow up 35Failed social support system 21
Erhardt and Cline 1998 (Lancet)
Over 50% preventable
Signs and Symptoms
Symptoms Signs Investigations
SOA Tachycardia Chest X-raySOBOE Increased JVP EchocardiogramFatigue Oedema Ambulatory ECGOrthopnoea Rales Exercise treadmillPND (Paroxysmal nocturnal dyspnoea)
Hepatomegaly Cardiac catheter
Nocturia AscitesAnorexia CardiomegalyWeight loss
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
CO=SVxHRBP=TPRxCO
Remembersymptoms haemodynamics symptoms survival
Remember
Starling’s Law: preload = force of contractionLapace’s Law: large heart = inefficient
cardiac output
cardiac workload
afterload
arterio-constriction
nor-epinephrine
aorticblood flow
SNS
Neurohormonal model of Heart Failure – Sympathetic Response
RememberCO = SV x HR
cardiac output
cardiac workload
Renal blood flow
RAS
angiotensin
aldosterone
Na+ and H2O retention
preloadafterload
arterio-constriction
remodelling
veno-constriction
Neurohormonal model of Heart Failure – renin-angiotensin-aldosterone
RememberStarlings
Law
cardiac output
cardiac workload
Renal blood flow
RAS
angiotensin
naturetic peptides
aldosterone
Na+ and H2O retention
preloadafterload
arterio-constriction
nor-epinephrine
aorticblood flow
SNS
veno-constriction
B-blockers
ACE-I
NEP-I
spironolactone
diuretics
nitrates
hydralazine
digoxin
Treatment of Heart Failure Remember
Survival = drug treatment
• 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 Diuretics
Role of ACE-inhibitors
• improves mortality (CONSENSUS)
• better than vasodilator therapy (VeHFT I and II)
• large well conducted trials
• preload (inhibits effect)
• afterload (inhibits vasoconstriction)
Side effects• hypotension (6%)
• hyperkalaemia (6%)
• cough (40%)
• dizziness (50%)
• raised serum creatinine (0.2%)
ACE
Ang (1-5)
angiotensinogen
renin
Ang I
Ang II
ACE
AT1 AT2 ATx
Ang (1-7)NEP
Potential Role of Angiotensin (1-7)
pressortrophic
antinatriuretic
depressorantitrophicnatriuretic
depressorantitrophicnatriuretic
angiotensinogen
renin
Ang I
Ang II
ACE
AT1 AT2 ATx
Ang (1-7)NEP
ACE
Ang (1-5)+
–
pressortrophic
antinatriuretic
depressorantitrophicnatriuretic
depressorantitrophicnatriuretic
ACEinhibitor
ACEinhibitor
Potential Role of Angiotensin (1-7)
icatibant
bradykinin
Ang II
Renin-Angiotensin/Kallikrein-Kinin Systemskininogen
kallikrein
inactive peptides
kininase II
angiotensinogen
renin
Ang I
ACE
B2 AT1 AT2
pressortrophic
antinatriuretic
depressorantitrophicnatriuretic
depressorantitrophic
cardioprotectiveNO
+
–
ACEinhibitor
B2 receptorknock-out
Landmark trials with ACE inhibitors in HF
Trial n EF% Drug Death Hospitalisation Follow up NNT(death)
CONSENSUS1987
253 <35%(IV)
enalapril 36 vs 50 reduced 1 year 6
SOLVD-P1992
4228 <35(I)
enalapril trend toreduction
reduced 4 years 104
SOLVD – T1991
2500 < 40(II-III)
enalapril 12.3 vs 15.5 reduced 3 years 31
ATLAS1997
3164 <35(II-IV)
lisinopril no difference reduced 4 years -
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 SRDigoxin in SR
– DIG trial DIG trial : no mortality benefit but reduction in : no mortality benefit but reduction in hospitalisations and improved symptomshospitalisations and improved symptoms
– useful in symptomatic patients where other drug useful in symptomatic patients where other drug therapy is optimisedtherapy is optimised
– should not be withdrawn from pts with HFshould not be withdrawn from pts with HF
• AnticoagulationAnticoagulation– if prolonged bed rest : prophylactic heparinif prolonged bed rest : prophylactic heparin– if LV dilatation / thrombus : chronic warfarin therapyif 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 hydralazineBenefit vs. placebo; inferior to enalapril (mortality)
Davies et al. BMJ 2000;320:428-431 Gibbs et al. BMJ 2000;320:495-498
However: 4-year mortality remains ~40%
Davies et al. BMJ 2000;320:428-431 Gibbs et al. BMJ 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 failurePharmaceutical Care Plan
Need for Drug : Diagnosis of CHF
Selection of Specific Drug: Symptom control - diuretics
Decrease mortality; ACE, B-blockers
Co-modibdity: anticoagulation
Patient factors
Selection of Regimen: Loading doses, maintenance dose
Drug factors
Provision of Drug: Timely, accurate
Administration of Drug: Timing, food
Monitor Effectiveness: Symptoms, pulse,cholesterol, side effects
Counsel / Educate: Expected effects, side effects
Risks vs benefits
Evaluate Effectiveness: Beneficial effects > detrimental effects??