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Heart Failure: The Scale of the Problem
Basic & Advanced Management
Dr Martin Thomas
Consultant CardiologistThe Heart Hospital, UCLH, London
20th October 2010
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 FailureThe Hillingdon Heart Failure Study
0
2
4
6
8
10
12
14
16
18
25-34 35-44 45-54 55-64 65-74 75-84 85+
Men Women
Incid
en
ce
(n
ew
cases/1
00
0
pop
ula
tion
/year)
Age group (years)
Prevalence of Heart FailureThe Echocardiographic Heart of England Study
0
5
10
15
20
25
45-54 55-64 65-74 75-84 85+
Men Women
Perc
en
tag
e w
ith
defi
nit
e h
eart
failu
re
Age group (years)
Davies et al, Lancet, 2001
Prevalence1/35 age 65-741/15 age 75-84
1/7 age >85
Heart Failure Admissions
British Heart Foundation, 2002
0 5 10 15 20 25 30
All diagnoses
All circulatory
Coronary Heart Disease
Angina
Acute MI
Heart failure
Stroke
Diabetes
All cancer
All nervous system
All respiratory system
All digestive system
All GU system
Complications of pregnancy and childbirth
Injuries and poisoning
Average duration of hospital admission (days)
Copyright ©2003 BMJ Publishing Group Ltd.
Stewart, S et al. Heart 2003;89:49-53
Projected Population with HF and GP consultations 2000-2020 (Scotland)
Copyright ©2003 BMJ Publishing Group Ltd.
Stewart, S et al. Heart 2003;89:49-53
Heart Failure Hospitalisation Burden 2000 to 2020 (Scotland)
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 Diuretics1950s : Thiazide Diuretics1960s : Loop Diuretics
1987 : ACE Inhibitors1997 : Beta - Blockers2000 : Spironolactone
Neurohormonal Response in Heart Failure
Decreased Cardiac Output
Decreased renal
Perfusion
Angiotensin II
Increased Aferload
Angiotensin Converting Enzyme
Renin
Aldosterone
Increased Preload
Sympathetic activation
Consensus and SOLVD studies
N Engl J Med. 1987 Jun 4;316(23):1429-35
N Engl J Med. 1991 Aug325 (5): 293-302
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
• 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
ARB Starting dose
Targetdose
Candesartan 2-4mg
OD
32mg
OD
Valsartan 40mg BD
160mg
BD
Losartan 50mg OD
150mg OD
HEAAL Study
0 1 2 3 4 50
10
20
30
40
50
Per
cent
age
of p
atie
nts
with
firs
t ev
ent
Losartan 50 mgLosartan 150 mg
Losartan 150 mg
Losartan 50 mg
Number of patients at risk
Hazard ratio: 0.90, p=0.027
1646
1683
1421
1492
1275
1343
1126
1205
644
711
% o
f P
atie
nts
with
Firs
t E
vent
HR 0.90 (0.82, 0.99)
P=0.027
Years1646 1422 1277 1126 644
1684 1493 1344 1205 711
Konstam MA et al, Lancet 2009; 374: 1840–48
CIBIS II
Lancet 1999; 353: 9–13
Packer M et al. N Engl J Med 2001;344:1651-1658
Effect of Carvedilol on Survival in Severe Chronic Heart Failure
2289 patients with Heart FailureNYHA Grade III or IV35% reduction in all cause mortality
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: 709-717
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
6800 patients in SRN Engl J Med 1997;336:525-33
Mortality Death or Hospital Admission
Taylor A et al. N Engl J Med 2004;351:2049-2057
V Heft Trial
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
•NYHA III/IV
•EF ≤ 35%
•SR
•OMT
•QRS >150msec
•QRS ≥120msec with dysynch
Biventricular Pacing
• 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
Catecholamines: +ve Inotropic Stimulation
Gs Gi
beta-receptor
Na+/Ca2+ex.Na+/K+exchanger
ATPcAMP (active)
AMP (inactive)
PDE
Rise in intracellular
calcium
Ca2+
Na+
K+
Dobutamine
MilrinonePDE III inhibitor
Digoxin
Na+risesCa2+
Inotropes : Mechanisms of Action
PKA
Phospholamban
Ca2+
• 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
Disadvantages of +ve Inotropic Stimulation
Actin
Tropomyosin
TnI
TnT
Ca2+
cTnC
Myosin head (S1 fragment)
LEVOSIMENDANCalcium sensitisation for enhanced cardiac contractility
Calcium sensitisation - enhanced systolic contraction of myofilaments - allows normal diastolic relaxation (inotropic and lusitropic effect of Levosimendan)
MORTALITY 26% for levosimendan and 38% for dobutamineMORTALITY 26% for levosimendan and 38% for dobutamine
p=0.029
Efficacy and safety of intravenous Levosimendan compared with
Dobutamine in severe low output heart failure (the LIDO study)
Follath F Follath F et alet al. Lancet 2002;360:196-202. Lancet 2002;360:196-202Follath F Follath F et alet al. Lancet 2002;360:196-202. 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-207AZairis MN, et al. J Am Coll Cardiol 2004; 43(Suppl 1):206A-207A
RUSSLAN study: 6 month mortality603 patients with acute HF post myocardial infarction
levosimendan vs. placebo
Moiseyev VS, et al. European Heart Journal 2002; 23:1422-1432
Levosimendan significantly lowered death rates by 40% during the first 14 days after treatment (p=0.031)
Ultrafiltration
UUltrafiltratioltrafiltrationn versus IV Diuretics for versus IV Diuretics for Patients HospitaPatients Hospitallized fized foor r AAcute cute
DDecompensated Congestive Heart ecompensated Congestive Heart Failure: A Prospective Randomized Failure: A Prospective Randomized
ClinicalClinical TrialTrial
UNLOAD TrialUNLOAD Trial
Worsening Heart Failure in 90 days
0.0220.022330330123123Days ReDays Re--hospitalizedhospitalized
P ValueP ValueSCSCUFUF
0.0090.00944442121(Unscheduled office + ED visits) %(Unscheduled office + ED visits) %
0.0220.0223.83.81.41.4Number of ReNumber of Re--hospitalization hospitalization days/patientdays/patient
0.0370.0370.460.460.220.22ReRe--hospitalizations/patienthospitalizations/patient
0.0220.02232321818Patients RePatients Re--hospitalized %hospitalized %
0.0220.022330330123123Days ReDays Re--hospitalizedhospitalized
P ValueP ValueSCSCUFUF
0.0090.00944442121(Unscheduled office + ED visits) %(Unscheduled office + ED visits) %
0.0220.0223.83.81.41.4Number of ReNumber of Re--hospitalization hospitalization days/patientdays/patient
0.0370.0370.460.460.220.22ReRe--hospitalizations/patienthospitalizations/patient
0.0220.02232321818Patients RePatients Re--hospitalized %hospitalized %
Circulatory Support
• Bridge to Transplantation
• Bridge to Recovery
• Destination Therapy
• 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 VADn=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