Heart Failure:
The Scale of the Problem
Basic & Advanced Management
20th October 2010
Dr Martin Thomas
Consultant Cardiologist
The Heart Hospital, UCLH, London
The Scale of the Problem
• Incidence: 1/1000 general population, rising 10%/year
• Prevalence: 900,000 patients in UK
• 1M inpatient bed stays: expected to increase 50% over
next 25 years
• 5% of all emergency admissions
• 2% total NHS budget
• 70% of cost = hospital admissions
• High readmission rate
The Incidence of Heart Failure
The Hillingdon Heart Failure Study
18
16
Incidence
(new cases/1000
population/year)
14
12
10
8
6
4
2
0
25-34 35-44 45-54 55-64 65-74 75-84
Age group (years)
Men
Women
85+
Prevalence of Heart Failure
Percentage with definite heart failure
The Echocardiographic Heart of England Study
25
20
Prevalence
1/35 age 65-74
1/15 age 75-84
1/7 age >85
15
10
5
0
45-54
55-64
65-74
75-84
85+
Age group (years)
Men
Women
Davies et al, Lancet, 2001
Heart Failure Admissions
Injuries and poisoning
Complications of pregnancy and childbirth
All GU system
All digestive system
All respiratory system
All nervous system
All cancer
Diabetes
Stroke
Heart failure
Acute MI
Angina
Coronary Heart Disease
All circulatory
All diagnoses
0
5
10
15
20
25
30
Average duration of hospital admission (days)
British Heart Foundation, 2002
Projected Population with HF
and GP consultations 2000-2020 (Scotland)
Stewart, S et al. Heart 2003;89:49-53
Copyright ©2003 BMJ Publishing Group Ltd.
Heart Failure Hospitalisation Burden
2000 to 2020 (Scotland)
Stewart, S et al. Heart 2003;89:49-53
Copyright ©2003 BMJ Publishing Group Ltd.
Heart Failure Mortality
• 30-40% mortality at 1 year after diagnosis!
• Subsequently <10% mortality per year
BUT Prognosis is improving
6 month mortality: 1995 – 26%
2005 – 14%
Heart Failure Mortality
Chronic heart failure
Implementing NICE guidance
August 2010
NICE clinical guideline 108
Treatment of Heart Failure
18th Century : Digitalis Folia
1920s : Mercurial Diuretics
1950s : Thiazide Diuretics
1960s : Loop Diuretics
1987 : ACE Inhibitors
1997 : Beta - Blockers
2000 : Spironolactone
Neurohormonal Response
in Heart Failure
Increased
Aferload
Renin
Decreased
Cardiac
Output
Sympathetic
activation
Decreased
renal
Perfusion
Increased
Preload
Angiotensin Converting Enzyme
Angiotensin
II
Aldosterone
Consensus and SOLVD studies
N Engl J Med.
1987 Jun
4;316(23):142
9-35
N Engl J Med.
1991 Aug
325 (5): 293302
Difficulties with ACE inhibitors
• Renal Failure
–
–
–
–
A rise in creatinine is expected with diuretics and ACEi
A 30% rise in creatinine is acceptable
An even greater fall in GFR is expected
Only contra-indicated in bilateral RAS
• Hypotension
– Ignore if asymptomatic
• Cough
– Reassure if not severe
– ARB if cough very difficult
Renal Failure and Hypotension
• Renal Failure (Creatinine >30% of baseline)
• Severe (symptomatic) hypotension
– If fluid overloaded (i.e. JVP elevated, oedema etc) refer
secondary care
– If not fluid overloaded, reduce diuretic and observe
patient and renal function
– Stop NSAIDs and other nephrotoxic drugs
– Stop drugs that drop BP
• Amlodipine, nitrates
• Rarely necessary to stop ACE
– Cessation of ACE will cause major clinical deterioration
– STOP SPIRONOLACTONE FIRST
Angiotensin II Receptor Blockers
ARB
• As alternative to ACE
only indicated in patients
with severe cough
– No difference in renal
failure; angioneurotic
oedema; hyperkalaemia
over ACE
• Can be added to ACE
inhibitors in patients
NYHA grade II-III
persistently symptomatic
Starting Target
dose
dose
Candesartan 2-4mg
OD
32mg
OD
Valsartan
40mg
BD
160mg
BD
Losartan
50mg
OD
150mg
OD
HEAAL Study
Losartan 50 mg
Losartan 150 mg
Percentage of patients with first event
% of Patients with First Event
50
40
HR 0.90
(0.82,
Hazard
ratio:
0.90,0.99)
p=0.027
P=0.027
30
20
10
0
0
1
2
3
4
5
Losartan 50 mg
1646
1646
1422
1421
1277
1275
1126
1126
644
644
Losartan 150 mg
1683
1684
1492
1493
1343
1344
1205
1205
711
711
Number of patients at risk
Years
Konstam MA et al, Lancet 2009; 374: 1840–48
CIBIS II
Lancet
1999; 353:
9–13
Effect of Carvedilol on Survival in
Severe Chronic Heart Failure
2289 patients with Heart
Failure
NYHA Grade III or IV
35% reduction in all cause
mortality
Packer M et al. N Engl J Med 2001;344:1651-1658
Beta Blockers
•
•
•
•
Only 4 licensed beta-blockers for HF
“Start low, go slow”
Up-titrate every 2 weeks
If deterioration – increase diuretics (temporary)
Carvedilol 3.125mg BD
Bisoprolol 1.25mg O.D.
Carvedilol 6.25mg BD
Bisoprolol 2.5mg O.D.
Carvedilol 12.5mg BD
Bisoprolol 3.75mg O.D.
Carvedilol 25mg BD
Bisoprolol 5mg O.D.
(50mg BD if >85kg)
Bisoprolol 7.5mg O.D.
Bisoprolol 10mg O.D.
Nebivolol : 1.25 -10mg O.D. ? In elderly
Spironolactone
•
•
•
•
•
•
•
•
Specific aldosterone antagonist
Up titrate ACEi before introduction
Do not use if Creat>200µmol/l (NICE)
Indicated in patients with NYHA grade III-IV
despite diuretics, ACE and Beta blockers
Watch K+ very carefully
Check U+Es at 1,4,8 and 12 weeks then 6,9 and
12 months then 6 monthly
Gynaecomastia
GI side effects
Rales Study
N Engl J
Med 1999
341: 709717
Digoxin
• Important use in patients with AF
• No effect on mortality
• Useful in patients unable to tolerate ACE
or ARB
• Very poor ventricular function
• Reduces frequency of hospital admissions
Dig Study
Mortality
Death or Hospital Admission
6800 patients in SR
N Engl J Med 1997;336:525-33
V Heft Trial
Taylor A et al. N Engl J Med 2004;351:2049-2057
Advanced Heart Failure Therapy
•
•
•
•
•
Device Therapy
Inotropic Support
Ultrafiltration
Circulatory Support
Cardiac Transplantation
Device Therapy in Heart Failure
Ventricular Dysynchrony:
• Intra- or inter-ventricular conduction delay
• Reduces diastolic filling time
• Prolonged mitral regurgitation
• Weakened contractility
• Reduced stroke volume & cardiac output
Wide QRS complex with LBBB morphology
Device Therapy in Heart Failure
Wide QRS associated with:
• Increased mortality (5X)
• Increased risk of sudden cardiac death
• 15% patients with HF have ventricular
dysynchrony
Biventricular Pacing
Biventricular Pacing
Biventricular Pacing
COMPANION (NEJM 2004) n=1520
• 34%  death/hospital admission (p<0.002)
• 24%  in all-cause mortality (p=0.059)
CARE-HF (NEJM 2005) n=813
• 37%  death/hospital admission (p<0.001)
• 36%  in all-cause mortality (p<0.002)
NICE Guidance
•NYHA III/IV
•EF ≤ 35%
•SR
•OMT
•QRS >150msec
•QRS ≥120msec with dysynch
Biventricular Pacing
Catecholamines: +ve Inotropic
Stimulation
• Currently the pharmacologic mainstay of inotropic
support
• Predictable pharmacodynamics and a favorable
pharmacokinetic profile
• Permit rapid titration of effects and undesiderable side
effects dissipate within minutes after cessation
• When catecholamines are combined, each substance
can be titrated according to the desired effects
Inotropes : Mechanisms of Action
Dobutamine
Ca2+
Digoxin
beta-receptor
Gs Gi
ATP
K+
Na+/K+exchanger
Ca2+
Na+
Na+/Ca2+ex.
Ca2+
Na+rises
cAMP (active)
PKA
Phospholamban
PDE
Milrinone
PDE III inhibitor
AMP (inactive)
Rise in
intracellular
calcium
Disadvantages of +ve Inotropic
Stimulation
• Important prognostic factor in heart failure
• ↑ MVO2 → energy depleted state and cell injury
• Stimulates arrythmias
• ? direct myocardial toxicity
• Stimulates lipolysis → FFA utilisation & ↓ efficieny for level
of MVO2
LEVOSIMENDAN
Calcium sensitisation for enhanced cardiac contractility
Actin
Tropomyosin
Ca2+
Myosin head (S1 fragment)
cTnC
TnI
TnT
Calcium sensitisation - enhanced systolic contraction of myofilaments - allows
normal diastolic relaxation (inotropic and lusitropic effect of Levosimendan)
Efficacy and safety of intravenous Levosimendan compared with
Dobutamine in severe low output heart failure (the LIDO study)
MORTALITY 26% for levosimendan and 38% for dobutamine
p=0.029
Follath F et al. Lancet 2002;360:196-202
CASINO STUDY n=299
Low-output HF: levo vs. dobut vs. placebo
Zairis MN, et al. J Am Coll Cardiol 2004; 43(Suppl 1):206A-207A
RUSSLAN study: 6 month mortality
603 patients with acute HF post myocardial infarction
levosimendan vs. placebo
Levosimendan significantly lowered death rates by 40% during
the first 14 days after treatment (p=0.031)
Moiseyev VS, et al. European Heart Journal 2002; 23:1422-1432
Ultrafiltration
Ultrafiltration versus IV Diuretics for
Patients Hospitalized for Acute
Decompensated Congestive Heart
Failure: A Prospective Randomized
Clinical Trial
UNLOAD Trial
Worsening Heart Failure in 90 days
UF
SC
P Value
Patients Re-hospitalized %
18
32
0.022
Re-hospitalizations/patient
0.22
0.46
0.037
1.4
3.8
0.022
123
330
0.022
21
44
0.009
Number of Re-hospitalization
days/patient
Days Re-hospitalized
(Unscheduled office + ED visits) %
Circulatory Support
• Bridge to Transplantation
• Bridge to Recovery
• Destination Therapy
Ventricular Assist Devices
• Extracorporeal assist devices (Thoratec/Abiomed)
• Implantable LV assist devices
- pulsatile (Heartmate)
- axial flow pumps (Heartware)
• Totally implantable LVAD (Lion Heart)
• Total Artificial Heart (ABIOCOR)
• Impella Device
Thoratec VAD
Heartmate VAD
Heartmate VAD
n=129
Quality of life
Heartware VAD
Heartware VAD
Cardiac Transplantation
• Estimated 700,000 cases of heart failure in the UK
• 7000 <65yrs
• 200,000 NYHA III/IV
Cardiac Transplantation
UK:
• 78 transplants
• 113 registered
USA:
• 2163 transplants
• 3384 registered
Conclusions
• Advanced heart failure management
– Currently reserved for small minority of patients
with end stage heart failure
– Increasing expertise
– May become common place with community use
– Development of advanced end of life strategies
• The future
– Stem cell therapy
– Xenografts
– Artificial hearts………
Any Questions?
Intra-aortic balloon counterpulsation
Inflate during early diastole
augmenting diastolic
pressure
Deflate during systole
reducing aortic volume and
decreasing afterload
Improves coronary diastolic
flow, decreases myocardial
systolic O2 demand
Intra-aortic balloon counterpulsation
32-40cc polyurethane
bladder mounted on flexible
shaft, tip just distal to left
subclavian artery
Inflated with helium (fast
inflation and deflation)
Triggered by ECG,
‘optimized’ by arterial
waveform