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