HEART FAILURE IN AUSTRALIA

A practical approach to a complex problem

Dr. Nathan DwyerBMedSci (Hons), MBBS (Hons), PhD, FRACP

DEFINITION OF HEART FAILURE

Heart failure is characterised by typical symptoms, which include:4

• Breathlessness

• Orthopnoea

• Paroxysmal nocturnal dyspnoea

• Ankle swelling

• Fatigue

• Reduced exercise tolerance

These symptoms may be accompanied by typical signs, such as:4

• Elevated jugular venous pressure

• Pulmonary crackles

• Peripheral oedema

HEART FAILURE IS A CLINICAL SYNDROME4

• Heart failure is a chronic progressive condition, punctuated by acute episodes2,5

• Each acute event results in further organ damage; myocardial and renal damage occurring

during such episodes may contribute to progressive left ventricular and/or renal dysfunction5

• Increasing frequency of acute events with disease progression leads to high rates

of hospitalisation and increased risk of mortality6

HEART FAILURE IS A COMPLEX SYNDROME INVOLVING

MULTIPLE ORGAN SYSTEMS AND IS ASSOCIATED WITH HIGH

RE-HOSPITALISATION AND MORTALITY RATES1–4

Adapted from Gheorghiade M et al. (2005).5

SYMPTOMS AND SIGNS OF HEART FAILURE ARE THE RESULT OF ABNORMALITIES OF CARDIAC STRUCTURE AND/OR FUNCTION7,8

• Abnormality of cardiac structure or function leads to failure of the heart to adequately perfuse organ systems8

• Weakening or stiffening of the heart muscle over time leads to pump failure and insufficient delivery of blood around the body7

DIFFERENT CO-MORBIDITIES AND PATHOPHYSIOLOGICAL PROCESSES CAN LEAD TO DIFFERENT TYPES OF HEART FAILURE9

There are two types of heart failure, distinguished by:4

• reduced ejection fraction (LVEF ≤40%*) (also called systolic heart failure, although patients may also exhibit diastolic abnormalities)

• preserved ejection fraction (LVEF ≥50%) (also called diastolic heart failure, although most patients have evidence of both systolic and diastolic dysfunction)

LVEF: left ventricular ejection fraction.

*Patients with an LVEF in the range of 40–49% represent a ‘grey area’,

which is defined as having primarily mild systolic dysfunction4

A range of risk factors and co-morbidities contribute to the development of heart failure9

DIFFERENT CO-MORBIDITIES AND PATHOPHYSIOLOGICAL PROCESSES CAN LEAD TO DIFFERENT TYPES OF HEART FAILURE9

HF: heart failure; HF-pEF: heart failure with preserved ejection fraction; HF-rEF: heart failure with reduced ejection fraction; LV: left ventricular;

MI: myocardial infarction.

Patients with an LVEF in the range of 40–49% represent a ‘grey area’,

which is defined as having primarily mild systolic dysfunction4

Many patients with heart failure appear asymptomatic or mildly symptomatic due to physiologic compensatory mechanisms. However, the underlying neurohormonal imbalance results in continued disease progression7

PERSISTENT NEUROHORMONAL IMBALANCE RESULTS IN CONTINUED DISEASE PROGRESSION10

NP: natriuretic peptide; RAAS: renin-angiotensin-aldosterone system; SNS: sympathetic nervous system.

THE SNS AND RAAS ARE OVER-ACTIVATED IN HEART FAILURE AND ARE RESPONSIBLE FOR MANY OF THE PATHOPHYSIOLOGICAL RESPONSES THAT CONTRIBUTE TO DISEASE PROGRESSION15,16

Ang: angiotensin; AT1R: angiotensin type 1 receptor; RAAS: renin-angiotensin-aldosterone system; SNS: sympathetic nervous system.

RAAS

VasoconstrictionBlood pressure

Sympathetic toneAldosteroneHypertrophy

Fibrosis

Ang II AT1R

HEART FAILURE

SYMPTOMS &

PROGRESSION

Adrenaline

Noradrenalineα1, β1, β2

receptors

VasoconstrictionRAAS activity

VasopressinHeart rate

Contractility

SNS

SECRETION OF NATRIURETIC PEPTIDES RESULTS IN A NUMBER OF RESPONSES THAT ACT TO REDUCE THE SYMPTOMS AND PROGRESSION OF HEART FAILURE17,18

NP: natriuretic peptide; NPR: natriuretic peptide receptor.

HEART FAILURE

SYMPTOMS &

PROGRESSION

INACTIVE

FRAGMENTS

VasodilationBlood pressureSympathetic toneNatriuresis/diuresisVasopressinAldosteroneFibrosisHypertrophy

NPRs NPs

NP system

AS HEART FAILURE ADVANCES, THE RAAS AND SNS BECOME THE PREDOMINANTLY ACTIVATED NEUROHORMONAL SYSTEMS15

Ang: angiotensin; AT1R: angiotensin type 1 receptor; NP: natriuretic peptide; NPR: natriuretic peptide receptor; RAAS: renin-angiotensin-aldosterone system;

SNS: sympathetic nervous system.

HEART FAILURE

SYMPTOMS &

PROGRESSION

INACTIVE

FRAGMENTS

VasodilationBlood pressureSympathetic toneNatriuresis/diuresisVasopressinAldosteroneFibrosisHypertrophy

NPRs NPs

NP system

RAAS

VasoconstrictionBlood pressure

Sympathetic toneAldosteroneHypertrophy

Fibrosis

Ang II AT1R

Adrenaline

Noradrenalineα1, β1, β2

receptors

VasoconstrictionRAAS activity

VasopressinHeart rate

Contractility

SNS

THE BURDEN OFHEART FAILURE

Heart failure in Australia

HEART FAILURE AFFECTS A LARGE NUMBER OF AUSTRALIANS EACH YEAR, PLACING A SIGNIFICANT BURDEN ON THE HEALTHCARE SYSTEM 2,19

†As there are no national data for heart failure in Australia, the Australian Institute of Health and Welfare has used overseas findings to estimate incidence in Australia.22

HEART FAILURE PREVALENCE IN AUSTRALIA

Adapted from AIHW (2011).22

Heart failure and oedema prevalence, by age and sex, 2007–200822

HEART FAILURE HOSPITALISATIONS

Adapted from AIHW (2011).22 Age-standardised to the 2001 Australian population.

Heart failure and cardiomyopathy hospitalisation rates, principal diagnosis by sex, 1993–1994 to 2007–200822

HEART FAILURE DEATHS

Adapted from AIHW (2011).22

Heart failure and cardiomyopathy death rates, by age and sex, 200722

CHALLENGES IN THE MANAGEMENT OF HEART FAILURE

Diagnosis of chronic heart failure

INITIAL DIAGNOSIS OF HEART FAILURE CAN BE COMPLEX8

BNP: B-type natriuretic peptide; ECG: electrocardiogram; MRI: magnetic resonance imaging; NT-proBNP: N-terminal pro-B-type natriuretic peptide.

DIAGNOSTIC ALGORITHM FOR A DIAGNOSIS OF HEART FAILURE OF NON-ACUTE ONSET4

Adapted from Ponikowski P et al (2016).4 aPatient reporting symptoms typical of heart failure. bNormal ventricular and atrial volumes and function. cConsider other causes of elevated natriuretic peptides.

BNP: B-type natriuretic peptide; CAD: coronary artery disease; ECG: electrocardiograph; MI: myocardial infarction; NT-proBNP: N-terminal pro-B type

natriuretic peptide.

• Symptoms and signs of heart failure are frequently confused with other conditions, or attributed to ageing, obesity, or lack of conditioning25-27

LACK OF CONSISTENT AND SPECIFIC SYMPTOMS MAKES HEART FAILURE DIFFICULT TO DIAGNOSE8,25

BNP: B-type natriuretic peptide; CCB: calcium channel blocker; COPD: chronic obstructive pulmonary disease; ECG: electrocardiograph;

NSAID: non-steroidal anti-inflammatory drug; NT-proBNP: N-terminal pro-B-type natriuretic peptide.

Other conditions that may present with similar symptoms26,27

Obesity Hypoalbuminaemia

Chest disease – including lung, diaphragm or chest wall Intrinsic renal or hepatic disease

Venous insufficiency in lower limbs Pulmonary embolic disease

Drug-induced ankle swelling (e.g. dihydropyridine CCBs) COPD

Depression and/or anxiety disorders Severe anaemia or thyroid disease

Drug-induced fluid retention (e.g. NSAIDs) Bilateral renal artery stenosis

• There is no single diagnostic test for heart failure25

• Several diagnostic tests must be used routinely to confirm a diagnosis of heart failure, e.g. ECG, chest X-ray, echocardiography, laboratory tests (including BNP/NT-pro BNP)8,24

A NUMBER OF DIAGNOSTIC ASSESSMENTS CAN BE USED TO SUPPORT THE PRESENCE OF HEART FAILURE8,26

BP: blood pressure; BNP: B-type natriuretic peptide; ECG: electrocardiogram; MI: myocardial infarction; NT-proBNP: N-terminal pro-B-type natriuretic peptide.

Assessment

of symptoms

Compatible symptoms include breathlessness, fatigue, angina, palpitations

or syncope

Assessment

of signs

Compatible signs should include appearance, pulse, BP, fluid overload, respiratory

and heart rate

ECG ECG changes are common (e.g. presence of new Q waves reflecting a MI; wave

abnormalities reflecting ischaemia, or an arrhythmia). If the ECG is completely

normal, heart failure, especially with systolic dysfunction, is unlikely (<10%)

Laboratory

analyses

Elevated BNP/NT-proBNP, hyponatraemia, renal dysfunction, mild elevations

of troponin

Chest X-ray Permits assessment of pulmonary congestion and may demonstrate important

pulmonary or thoracic causes of dyspnoea

Echocardiography Provides extensive information on cardiac anatomy, wall motion and valvular

and ventricular function; used to confirm heart failure diagnosis

CHALLENGES IN THE MANAGEMENT OF HEART FAILURE

Treatment of chronic heart failure

WHAT ARE THE TREATMENT OBJECTIVES FOR PATIENTS WITH CHRONIC HEART FAILURE?

Adapted from Dickstein K et al. (2008).26

Objectives of treatment for chronic heart failure8,26

AUSTRALIAN GUIDELINES FOR HEART FAILURE (2011) RECOMMEND A NUMBER OF NON-PHARMACOLOGICAL AND PHARMACOLOGICAL INTERVENTIONS28

ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin-receptor blocker.

This is not an exhaustive list of management recommendations. Refer to the

National Heart Foundation of Australia Guidelines for the prevention, detection

and management of chronic heart failure in Australia (2011) for further reference.

PARADIGM-HF (2014)4

8,442 patients(ARNI ) vs. ACEi:

20% CV mortality or

heart failure hospitalisation

LANDMARK TRIALS IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION

Percentages are relative risk reductions vs. comparator.

ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin-receptor blocker; ARNI: angiotensin receptor-neprilysin inhibitor; CHARM:

Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity; CIBIS: Cardiac Insufficiency Bisoprolol Study II; CV: cardiovascular;

EMPHASIS-HF: Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure; MRA: mineralocorticoid receptor antagonist;

PARADIGM-HF: Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure; SHIFT: Systolic

Heart Failure Treatment with the If Inhibitor Ivabradine Trial; SOLVD-T: Studies of Left Ventricular Dysfunction Treatment.

CIBIS-II (1999)32

2,647 patients (beta-blocker) vs. placebo:

34% all-cause mortality

EMPHASIS-HF (2011)34

2,737 patients (MRA) vs. placebo:

37% CV mortality or

heart failure hospitalisation

SHIFT (2010)31

6,558 patients(If inhibitor) vs. placebo:

18% CV death or heart

failure hospitalisation

SOLVD-T (1991)29

2,569 patients (ACEI) vs. placebo:

16% all-cause mortality

CHARM-Alternative

(2003)30

2,028 patients (ARB) vs. placebo:

23% CV mortality or

heart failure hospitalisation

CHARM-Added (2003)33

2,548 patients (ARB) vs. placebo:

15% CV mortality or heart

failure hospitalisation

1990s 2000s 2010s

UPDATED 2016 ESC HEART FAILURE GUIDELINE RECOMMENDATIONS4

Adapted from Ponikowski P et al. (2016).4 *Or ARB if ACEI is not tolerated/contraindicated. †Patient should have elevated natriuretic peptides (plasma

BNP ≥150 pg/mL or plasma NT-proBNP ≥600 pg/mL, or if HF hospitalisation within the last 12 months, plasma BNP ≥100 pg/mL or plasma NT-proBNP

≥400 pg/mL) and able to tolerate enalapril 10 mg twice daily.

ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin-receptor blocker; ESC: European Society of Cardiology; HF: heart failure; HF-rEF:

heart failure with reduced ejection fraction; MRA: mineralocorticoid receptor antagonist.

Therapy Recommendation Class Level

ACEIsAn ACEI* is recommended, in addition to a beta-blocker, for symptomatic patients with HF-rEF

to reduce the risk of HF hospitalisation and death.I A

ARBs

An ARB is recommended to reduce the risk of HF hospitalisation and cardiovascular death in

symptomatic patients unable to tolerate an ACEI (patients should also receive a beta-blocker and an

MRA).

An ARB may be considered to reduce the risk of HF hospitalisation and death

in patients who are symptomatic despite treatment with a beta-blocker who are

unable to tolerate an MRA.

I

IIb

B

C

Beta-blockersA beta-blocker is recommended, in addition an ACEI*, for patients with stable, symptomatic HF-rEF

to reduce the risk of HF hospitalisation and death.I A

Aldosterone

antagonists

An MRA is recommended for patients with HF-rEF, who remain symptomatic despite treatment with

an ACEI* and a beta-blocker, to reduce the risk of HF hospitalisation and death.I A

Diuretics

Diuretics are recommended in order to improve symptoms and exercise capacity in patients with

signs and/or symptoms of congestion.

Diuretics should be considered to reduce the risk of HF hospitalisation in patients with signs and/or

symptoms of congestion.

I

IIa

A

B

Angiotensin receptor

neprilysin inhibitor

(ARNI)

An ARNI is recommended as a replacement for an ACEI to further reduce the risk of HF

hospitalisation and death in ambulatory patients with HF-rEF who remain symptomatic despite

optimal treatment with an ACE-I, a beta-blocker and an MRA.†I B

THE UPDATED 2016 ESC HEART FAILURE GUIDELINES THERAPEUTIC ALGORITHM FOR A PATIENT WITH SYMPTOMATIC HF-rEF4

2016 ACC/AHA/HFSA FOCUSED UPDATE ON NEW PHARMACOLOGICAL THERAPY FOR HEART FAILURE: AN UPDATE OF THE 2013 ACCF/AHA GUIDELINE FOR THE MANAGEMENT OF HEART FAILURE

Adapted from Yancy CW et al. (2016 ).35

ACC: American College of Cardiology; ACCF: American College of Cardiology Foundation; ACEI: angiotensin-converting enzyme inhibitor;

AHA: American Heart Association; ARB: angiotensin-receptor blocker; ARNI: angiotensin receptor-neprilysin inhibitor; COR: class (strength)

of recommendation; GDEM: guideline-directed evaluation and management; HF-rEF: heart failure with reduced ejection fraction; HFSA: Heart

Failure Society or America; LOE: level (quality) of evidence; LVEF: left ventricular ejection fraction; MRA: mineralocorticoid receptor antagonist;

NYHA: New York Heart Association.

COR LOE Recommendation

I

ACE: A The clinical strategy of inhibition of the renin-angiotensin system with ACE inhibitors (Level of Evidence: A),

OR ARBs (Level of Evidence: A), OR ARNI (Level of Evidence: B-R) in conjunction with evidence-based beta

blockers, and aldosterone antagonists in selected patients, is recommended for patients with chronic HF-rEF to

reduce morbidity and mortality.

ARB: A

ARNI: B-R

I ACE: AThe use of ACE inhibitors is beneficial for patients with prior or current symptoms of chronic HF-rEF

to reduce morbidity and mortality.

I ARB: AThe use of ARBs to reduce morbidity and mortality is recommended in patients with prior or current symptoms

of chronic HF-rEF who are intolerant to ACE inhibitors because of cough or angioedema.

I ARNI: B-RIn patients with chronic symptomatic HF-rEF NYHA class II or III who tolerate an ACE inhibitor or ARB,

replacement by an ARNI is recommended to further reduce morbidity and mortality.

III Harm B-RARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose

of an ACE inhibitor.

III Harm C-EO ARNI should not be administered to patients with a history of angioedema

IIa B-R

If inhibitor can be beneficial to reduce HF hospitalisation for patients with symptomatic

(NYHA class II–III) stable chronic HF-rEF (LVEF ≤35%) who are receiving GDEM,

including a beta blocker at maximum tolerated dose, and who are in sinus rhythm

with a heart rate of 70 beats per minute or greater at rest.

Renin-Angiotensin System Inhibition with Angiotensin-Converting Enzyme Inhibitor

or Angiotensin Receptor Blocker or ARNI: Recommendations35

GUIDELINES FOR HFpEF: FOCUS ON MANAGEMENT OF SYMPTOMS AND CO-MORBIDITIES24

Adapted from Yancy CW et al. (2013).24

ACCF: American College of Cardiology Foundation; ACEI: angiotensin-converting enzyme inhibitor; AF: atrial fibrillation; AHA: American Heart Association;

ARB: angiotensin-receptor blocker; CAD: coronary artery disease; GDMT: guideline-directed medical therapy; HF: heart failure; HF-pEF: heart failure with

preserved ejection fraction; LVEF: left ventricular ejection fraction.

ACCF/AHA recommendations for the treatment of HF-pEF

Class of

recommendation

Level of

evidence

Systolic and diastolic blood pressure should be controlled according

to published clinical practice guidelines

I B

Diuretics should be used for relief of symptoms due to volume

overload (irrespective of LVEF)

I C

Coronary revascularisation for patients with CAD in whom angina

or demonstrable myocardial ischemia is present despite GDMT

IIa C

Management of AF according to published clinical practice guidelines

for HF-pEF to improve symptomatic HF

IIa C

Use of beta-blockers, ACEIs and ARBs for hypertension in HF-pEF IIa C

ARBs might be considered to decrease hospitalisations in HF-pEF IIb B

Nutritional supplementation is not recommended in HF-pEF III: no benefit C

• Coordination of care along the continuum of heart failure is crucial to achieving the goal of heart failure management – providing a ‘seamless’ system of care, optimising the management of patients8

• Multidisciplinary management programs have been reported to reduce rates of heart failure hospitalisation, all-cause hospitalisation and mortality in patients with heart failure when compared with usual care*24,36,37

MULTIDISCIPLINARY STRATEGIES OPTIMISE THE MANAGEMENT OF PATIENTS WITH HEART FAILUREAND IMPROVE PATIENT OUTCOMES24,36,37

*Data from two meta-analyses.

THE BURDEN OF HEART FAILURE

Quality of life

• Heart failure can severely affect patients’ social capacity and emotional health38-40

• 76% of patients struggle to perform their daily activities

• 63% of patients reported symptoms that are consistent with depression

• >50% of patients reported difficulty with recreational pastimes, sports or hobbies

• 40% of patients struggle to socialise or engage in daily routine activities with friends or family

HEART FAILURE SIGNIFICANTLY IMPACTS QUALITY OF LIFE38–40

Impact of heart

failure

Number of patients

reporting impact (n=15)

Physical mobility 14/15

Physical activity

limitations14/15

Daily activities 12/15

Emotional impacts 11/15

Lifestyle 11/15

Self-care 3/15

Sleep disturbance 3/15

Concepts frequently reported as

important by patients with heart failure41

• Quality of life for patients with heart failure is:38

• Worse than those with diabetes

• Similar to those with Parkinson’s disease or motor neuron disease

• Patients may require assistance with daily activities such as taking their medication42,43

• Caregiver burden can be substantial43,44

QUALITY OF LIFE IS WORSE IN PATIENTS WITH HEART FAILURE THAN IN THOSE SUFFERING FROM OTHER CHRONIC CONDITIONS38

Adapted from Calvert MJ et al. (2005).38 Survey study assessing quality of life of patients with heart failure due to left ventricular dysfunction

(NYHA III or IV) (n=813) using the EQ-5D and Minnesota Living with Heart Failure Questionnaire.

HF: heart failure; NYHA: New York Heart Association.

0 0.2 0.4 0.6 0.8 1

EQ-5D Index score

General population

General population age 65–74

HF patients NYHA III/IV

Type 2 diabetes

Mild motor neuron disease

Moderate motor neuron disease

Parkinson’s disease

Hospitalised after ischaemic stroke

3-month assessment post-stroke

Non–small cell lung cancer

Mean EQ-5D in patients with NYHA class III/IV heart failure compared with general population and other chronic diseases38

• There is a clear relationship between symptom severity and survival

• Even patients with mild symptoms may have an increased riskof hospitalisation and death

• If heart failure deteriorates, the patient may be described as ‘decompensated’

• This may happen suddenly or slowly

• If hospitalisation is the outcome than this event is of considerableprognostic importance

• Symptoms and signs may resolve post a decompensation but the underlying cardiac dysfunction may not

• This leaves patients at risk of recurrent decompensation

SYMPTOMS ARE PREVALENT AND ARE PREDICTORS FOR WORSE OUTCOMES4,45

Non-compliance

Arrhythmia

Ischaemia

Medication (NSAID, prednisolone)

Valvular deterioration

REASONS FOR HEART FAILURE DECOMPENSATIONS

HEART FAILURE PRESENTS WITH A WIDE RANGE OF SYMPTOMS, OF WHICH DYSPNOEA IS ALMOST UNIVERSAL46

Adapted from Goldberg RJ et al. (2010).46 Retrospective clinical audit examining the type and frequency of symptoms in patients hospitalised

with acute heart failure between 1995 and 2000 (n=4537).

Signs and symptoms in 4,537 residents of Worcester, Massachusetts, USA, hospitalised for acute heart failure between 1995 and 200046

• Heart failure can be graded according to NYHA functional classification8

• NYHA functional classification is widely used and accepted and is based on exercise capacity and symptoms of the disease8

NEW YORK HEART ASSOCIATION (NYHA) CLASSIFICATION IS IMPORTANT FOR EVALUATING THE SYMPTOMS OF PATIENTS WITH HEART FAILURE8

Adapted from McMurray JJ et al. (2012).8

NYHA class I NYHA class II NYHA class III NYHA class IV

No limitation of physical

activity

Slight limitation of physical

activity

Marked limitation of physical

activity

Unable to carry on any physical

activity without discomfort

No overt symptoms

Comfortable at rest, but ordinary

physical activity causes

symptoms of heart failure

Comfortable at rest, but less than

ordinary activity causes

symptoms of heart failure

Presence of symptoms

even at rest

NYHA classes

Stage Patient Description

High risk for

developing heart

failure

• Hypertension

• Coronary artery disease

• Diabetes mellitus

• Family history of cardiomyopathy

Asymptomatic

heart failure

• Previous myocardial infarction

• Left ventricular systolic dysfunction

• Asymptomatic valvular disease

Symptomatic heart

failure

• Known structural heart disease

• Shortness of breath and fatigue

• Reduced exercise tolerance

Refractory

end-stage heart

failure

• Marked symptoms at rest despite maximal medical therapy (e.g., those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions)

ACC/AHA Staging System for Heart Failure

Hunt SA, et al. Circulation 2001;104:2996-3007.

A

B

C

D

• In a patient with established heart failure4

• Symptoms and signs of heart failure should be assessed at each visit

• Particular attention should be given to evidence of congestion

• Persistence of symptoms despite treatment often indicates the need for additional therapy

HEART FAILURE SYMPTOMS

Adapted from Ponikowski P et al. (2016).4

Worsening symptoms are serious4

Patients with worsening heart failure

symptoms are at risk of urgent

hospitalisation and death

THE BURDEN OFHEART FAILURE

Hospitalisations

HEART FAILURE PATIENTS ARE AT HIGH RISK OF REPEATED HOSPITALISATIONS40,47

HF: heart failure; NYHA: New York Heart Association.

HOSPITALISATION FOR ACUTE HEART FAILURE IS ASSOCIATED WITH SIGNIFICANT MORTALITY47,50-52

*Data from European patients hospitalised for heart failure in the European Society of Cardiology Heart Failure (ESC-HF) Pilot study and EuroHeart

Failure Survey (EHFS) II. †Analysis of heart failure data from 1,282 incident cases of heart failure in the Atherosclerosis Risk in Communities (ARIC)

population-based study of individuals from four communities in the USA (1987–2002) (n=15,792).

1year

~20%

mortality after

1 year*47

30days

4–7%

in-hospital

mortality

rate*50,51

~10%

mortality after

30 days†52

EACH TIME A PATIENT IS HOSPITALISED FOR HEART FAILURE, THEIR MORTALITY RISK INCREASES53

Adapted from Lee DS et al. (2009).53 Retrospective clinical audit examining the ‘dose-dependent’ relationship between heart failure events and death in

patients with heart failure (n=9138) in the Enhanced Feedback For Effective Cardiac Treatment Study.

Risk of mortality during a median follow-up of 1,024 days, according to the number of re-hospitalisations for heart failure53

MEAN LENGTH OF HOSPITAL STAY INCREASES WITH EACH RE-HOSPITALISATION FOR HEART FAILURE54

Adapted from Korv es et al. (2010).54 278,307 patients in the USA with ≥1 hospitalisation with a heart failure claim were followed

from first heart failure hospitalisation for 24 months or until disenrollment or end of data availability.

HF: heart failure; HF-pEF: heart failure with preserved ejection fraction; HF-rEF: heart failure with reduced ejection fraction.

Length of stay following hospitalisation for heart failure54

• Congestion is the most frequent cause of readmissions for heart failure

• Other factors include age, co-morbidities, premature discharge and medication non-adherence

• Each readmission is associated with poorer long-term outcomes and significant increases in heart failure related health costs

• With every readmission for heart failure, quality of life declines

RECURRENT HOSPITALISATIONS ADVERSELY AFFECT QUALITY OF LIFE55

THE BURDEN OFHEART FAILURE

Mortality

• All patients with heart failure, regardless of their symptoms, have a poor prognosis48

• Within 3 years, 34% of NYHA class I and II patients, and 42% of NYHA class III and IV patients die48

CHRONIC HEART FAILURE HAS A SIGNIFICANT IMPACT ON LONG-TERM PROGNOSIS IN PATIENTS48

NYHA: New York Heart Association.

5years

~50%

mortality after

onset of heart

failure56-58

A HIGH PROPORTION OF DEATHS IN PATIENTS WITH HEART FAILURE OCCUR SUDDENLY AND UNEXPECTEDLY8

Adapted from MERIT-HF (1999).59 Randomised, double-blind trial assessing the the effect on mortality of metoprolol controlled release/extended release

once daily, in addition to standard therapy, compared to placebo and standard therapy, in 3991 patients with chronic heart failure in NYHA class II–IV

with ejection fraction ≤0.4. Primary endpoint was all-cause mortality, analysed by intention to treat.

CHF: chronic heart failure; MERIT-HF: Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure; NYHA: New York Heart Association.

• Sudden cardiac death accounts for approximately half of deaths in patients with heart failure8,59,60

• The proportion of sudden cardiac deaths varies according to NYHA class and is greater in patients with mild-to-moderate symptoms (NYHA classes II and III)59,60

8,59,60

NYHA II

64%

12%

24%

n=103

NYHA III

59%

26%

15%

n=103

33%

56%

11%

NYHA IV

n=27

CHF

Other

Sudden Death

Severity of heart failure and mode of death in the MERIT-HF trial59

FOR MANY PATIENTS HEART FAILURE IS ASSOCIATED WITH A WORSE PROGNOSIS THAN ADVANCED CANCERS, INCLUDING BOWEL, PROSTATE AND BREAST CANCER61

Adapted from Stewart S et al. (2001).61 Retrospective clinical audit comparing five-year survival rates and associated loss of expected life-years of

male and female patients hospitalised for heart failure (n=3241 and n=3606, respectively) or MI (n=6932 and n=4916, respectively), or cancer of the

lung, large bowel, prostate or bladder in male patients (n=6051) or cancer of the breast, lung, large bowel or ovary in female patients (n=6320).

HF: heart failure; MI: myocardial infarction.

Five-year survival following first admission to any Scottish hospital in 1991 for HF, MI and the four most common cancers in men and women61

• Survival rates in chronic heart failure have improved with the introduction of new therapies8

MORTALITY IN HF-REF REMAINS HIGH DESPITE THE INTRODUCTION OF NEW THERAPIES THAT IMPROVE SURVIVAL8

*In addition to standard therapy at the time of study (except in CHARM-Alternative where background ACEI therapy was excluded). Patient populations

varied between trials and as such relative risk reductions cannot be directly compared. SOLVD (Studies of Left Ventricular Dysfunction), CIBIS-II (Cardiac

Insufficiency Bisoprolol Study II) and RALES (Randomized Aldactone Evaluation Study) enrolled chronic HF patients with LVEF ≤35%. CHARM-

Alternative (Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity) enrolled chronic HF patients with LVEF ≤40%.

ACEI: angiotensin-converting-enzyme inhibitor; ARB: angiotensin-receptor blocker; ARR: absolute risk reduction; HF: heart failure; HF-rEF: heart failure

with reduced ejection fraction; LVEF: left ventricular ejection fraction; MRA: mineralocorticoid receptor antagonist.

16%(4.5% ARR; mean follow

up of 41.4 months)

SOLVD18,29

34%(5.5% ARR; mean follow

up of 1.3 years)

CIBIS-II32

Red

uc

tio

n i

n r

ela

tive

ris

k o

f

mo

rtali

ty v

s p

lac

eb

o

30%(11.0% ARR; mean follow

up of 24 months)

RALES62

17%(3.0% ARR; median follow

up of 33.7 months)

CHARM

-Alternative30

ACEI* Beta-blocker* MRA* ARB*

• However, significant mortality remains: ~50% of patients die within 5 years of diagnosis24,56-58

THE BURDEN OFHEART FAILURE

The Carer

• Caregiving tasks related to feelings of burden include:63

• personal care, such as assisting with washing and bathing, and moving in and around the house

• Caregiving burden in partners of patients with heart failure is similar to that in partners of patients with cancer63

• Heart failure caregivers report being socially isolated, physically exhausted and unprepared for the stress of the caregiver role, with sleep and anxiety issues over current and future needs, and worry over financial concerns44

• Older caregivers experience decreased physiological functioning, increased risk of health problems, and increased risk of mortality64

• caregivers experiencing heightened emotional strain from caregiving also face a greatly increased mortality

HEART FAILURE IMPOSES A SIGNIFICANT BURDEN ON THE CARER63

• Heart failure is a chronic progressive condition, punctuated by acute events65

• The RAAS and SNS are over-activated and the resulting neurohormonalimbalance contributes to disease progression in patients with heart failure,including those who appear asymptomatic or mildly symptomatic7,15-17,66,67

• All patients with heart failure are at high risk of experiencing mortality47,52,56,57

and frequent, repeated hospitalisations40,47

• Heart failure places a significant burden on patients, with a negative effect on quality of life38-40

• Diagnosis of heart failure can be difficult due to the non-specific nature of heart failure symptoms4

• Recommended drugs for the treatment of HF-rEF include ACEIs (or ARBs),ARNI, aldosterone antagonists, beta-blockers and diuretics4,35

• Guidelines recommend a multidisciplinary approach to the management of heart failure, which may improve patient outcomes4

SUMMARY

ACEI: angiotensin-converting-enzyme inhibitor; ARB: angiotensin-receptor blocker; ARNI: angiotensin receptor-neprilysin inhibitor; HF-rEF: heart failure

with reduced ejection fraction; RAAS: renin-angiotensin-aldosterone system; SNS: sympathetic nervous system.

1. National Heart Foundation of Australia. Diagnosis and management of chronic heart failure. Quick reference guide for health professionals,updated October 2011. Available at https://heartfoundation.org.au/images/uploads/publications/CHF-QRG-updated-2014.pdf. Accessed June 2016.

2. National Heart Foundation of Australia. A systematic approach to chronic heart failure care: a consensus statement. Melbourne: National Heart Foundation of Australia, 2013. Available at https://heartfoundation.org.au/images/uploads/publications/HF_CHF_consensus_web_FINAL_SP.pdf. Accessed June 2016.

3. McMurray JJ et al. Eur J Heart Fail 2013;15:1062–73.

4. Ponikowski P et al. Eur Heart J 2016 [epub ahead of print].

5. Gheorghiade M et al. Am J Cardiol 2005;96:11G–7G.

6. Mosterd A et al. Heart 2007;93:1137–46.

7. Fauci AS, et al. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008.

8. McMurray JJ et al. Eur Heart J 2012;33:1787–847.

9. Krum H et al. Lancet 2003;362:147–58.

10. Francis G et al. Ann Intern Med 1984;101:370–7.

11. von Lueder TG et al. Circ Heart Fail 2013;6:594–605.

12. Clerico A et al. Am J Physiol Heart Circ Physiol 2011;301:H12–20.

13. Luchner A et al. Cardiovasc Res 2004;63:443–9.

14. Thygesen K et al. Eur Heart J 2012;33:2001–6.

15. Kemp CD et al. Cardiovasc Pathol 2012;21:365–71.

16. Schrier RW et al. N Engl J Med 1999;341:577–85.

17. Levin ER et al. N Engl J Med 1998;339:321–8.

18. Mangiafico S et al. Eur Heart J 2013;34:886–93c.

19. National Heart Foundation of Australia. Australian Heart Disease Statistics 2014. Available at http://www.heartfoundation.org.au/SiteCollectionDocuments/HeartStats_2014_web.pdf. Accessed June 2016.

20. BEACH. Management of heart failure in general practice patients. 2015.

REFERENCES

21. Australian Bureau of Statistics. 3222.0 - Population Projections, Australia, 2012 to 2101. Available at http://www.abs.gov.au/AUSSTATS/abs@.nsf/Latestproducts/3222.0Main Features32012 (base) to 2101?opendocument&tabname=Summary&prodno=3222.0&issue=2012%20(base)%20to%202101&num=&view=. Accessed September 2015.

22. Australian Institute of Health and Welfare 2011. Cardiovascular disease: Australian facts 2011. Cardiovascular disease series. Cat. no. CVD 53. Canberra: AIHW.

23. Australian Bureau of Statistics, 3303.0 - Causes of Death, Australia, 2013 Available at http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/by Subject/3303.0~2013~Main Features~Leading Causes of Death~10001. Accessed July 2015.

24. Yancy CW et al. J Am Coll Cardiol 2013;62:e147–239.

25. Hunt SA et al. J Am Coll Cardiol 2009;53:e1–e90.

26. Dickstein K et al. Eur Heart J 2008;29:2388–442.

27. National Institute for Clinical Excellence (NICE). Chronic heart failure clinical guideline 5; July 2003.

28. National Heart Foundation of Australia. Guidelines for the prevention, detection and management of chronic heart failure in Australia. October 2011. Available at http://www.heartfoundation.org.au/SiteCollectionDocuments/Chronic_Heart_Failure_Guidelines_2011.pdf. Accessed July 2016.

29. SOLVD Investigators. N Engl J Med 1991;325:293–302.

30. Granger CB et al. Lancet 2003;362:772–6.

31. Swedberg K et al. Lancet 2010;376:875–85.

32. CIBIS-II Investigators. Lancet 1999;353:9–13.

33. McMurray JJ et al. Lancet 2003;362:767–71.

34. Zannad F et al. N Engl J Med 2011;364:11–21.

35. Yancy CW et al. J Am Coll Cardiol 2016 [epub ahead of print].

36. Holland R et al. Heart 2005;91:899–906.

37. McAlister FA et al. J Am Coll Cardiol 2004;44:810–9.

38. Calvert MJ et al. Eur J Heart Fail 2005;7:243–51.

39. Moser DK et al. Heart Lung 2010;39:378–85.

40. Cowie MR et al. ESC Heart Failure 2014;1:110–45.

REFERENCES

41. Gwaltney et al. Presented at the American Heart Association Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke 2010 Scientific Sessions, Washington, D.C., May 19–21, 2010.

42. Boyd KJ et al. Eur J Heart Fail 2004;6:585–91.

43. Clark AM et al. J Adv Nurs 2008;61:373–83.

44. Saunders MM. West J Nurs Res 2008;30:943–59.

45. Smith DH et al. Perm J 2011;15:4–11.

46. Goldberg RJ et al. Clin Cardiol 2010;33:E73–80.

47. Maggioni AP et al. Eur J Heart Fail 2013;15:808–17.

48. Ahmed A. Am J Cardiol 2007;99:549–53.

49. Krumholz HM et al. Circ Cardiovasc Qual Outcomes 2009;2:407–13.

50. Maggioni AP et al. Eur J Heart Fail 2010;12:1076–84.

51. Nieminen MS et al. Eur Heart J 2006;27:2725–36.

52. Loehr LR et al. Am J Cardiol 2008;101:1016–22.

53. Lee DS et al. Am J Med 2009;122:162–9 e1.

54. Korves et al. Presented at the American Heart Association Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke 2010 Scientific Sessions, Washington, D.C., May 19–21, 2010.

55. Nieminen MS et al. Int J Cardiol 2015;191:256–64.

56. Roger VL et al. JAMA 2004;292:344–50.

57. Levy D et al. N Engl J Med 2002;347:1397–402.

58. Go AS et al. Circulation 2014;129:e28–e292.

59. MERIT-HF. Lancet 1999;353:2001–7.

60. Desai AS et al. Eur Heart J 2015;36:1990–7.

REFERENCES

61. Stewart S et al. Eur J Heart Fail 2001;3:315–22.

62. Pitt B et al. N Engl J Med 1999;341:709–17.

63. Luttik ML et al. Eur J Heart Fail 2007;9:695–701.

64. Schulz R et al. JAMA 1999;282:2215–19.

65. Gheorghiade M et al. J Am Coll Cardiol 2009;53:557–73.

66. Nathisuwan S et al. Pharmacotherapy 2002;22:27–42.

67. Schrier RW et al. Kidney Int 2000;57:1418–25.

REFERENCES

ADDITIONAL SLIDES

GUIDELINES FOR THE PREVENTION, DETECTION AND MANAGEMENT OF CHRONIC HEART FAILURE IN AUSTRALIA 201128

Adapted from National Heart Foundation of Australia. Guidelines for the prevention, detection and management of chronic heart failure in Australia (2011).28

ACEI: angiotensin-converting-enzyme inhibitor; bpm: beats per minute; CHF: chronic heart failure; LV: left ventricular; LVEF: left ventricular ejection fraction;

NYHA: New York Heart Association.

Recommendations for PHARMACOLOGICAL treatment of symptomatic CHFGrade of

recommendation*

First-line agents

ACEIs, unless not tolerated or contraindicated, are recommended for all patients with systolic heart failure

(LVEF <40%), whether symptoms are mild, moderate or severe.A

Every effort should be made to increase doses of ACEIs to those shown to be of benefit in major trials. If this is not

possible, a lower dose of ACEI is preferable to none at all.B

Diuretics should be used, if necessary, to achieve euvolaemia in fluid-overloaded patients. In patients with systolic LV

dysfunction, diuretics should never be used as monotherapy, but should always be combined with an ACEI to maintain

euvolaemia.

D

Beta-blockers are recommended, unless not tolerated or contraindicated, for all patients with systolic CHF who remain

mildly to moderately symptomatic despite appropriate doses of an ACEI.A

Beta-blockers are also indicated for patients with symptoms of advanced CHF. B

Aldosterone receptor blockade with spironolactone is recommended for patients who remain severely symptomatic,

despite appropriate doses of ACEIs and diuretics.B

Aldosterone receptor blockade with spironolactone is recommended for patients who remain severely symptomatic,

despite appropriate doses of ACEIs and diuretics.B

Angiotensin II receptor antagonists may be used as an alternative in patients who do not tolerate ACEIs due

to kinin-mediated adverse effects (e.g. cough). They should also be considered for reducing morbidity and mortality

in patients with systolic CHF who remain symptomatic despite receiving ACEIs.

A

Direct sinus node inhibition with ivabradine should be considered for CHF patients with impaired systolic function

and a recent heart failure hospitalisation who are in sinus rhythm where their heart rate remains >70 bpm despite efforts

to maximise dosage of background beta-blockade.

B

GUIDELINES FOR THE PREVENTION, DETECTION AND MANAGEMENT OF CHRONIC HEART FAILURE IN AUSTRALIA 201128

Adapted from National Heart Foundation of Australia. Guidelines for the prevention, detection and management of chronic heart failure in Australia (2011).28

ACEI: angiotensin-converting-enzyme inhibitor; AF: atrial fibrillation; ARB: angiotensin-receptor blocker; CHD: coronary heart disease; CHF: chronic heart failure.

Recommendations for PHARMACOLOGICAL treatment of symptomatic CHFGrade of

recommendation*

Second-line agents

Digoxin may be considered for symptom relief and to reduce hospitalisation in patients with advanced CHF.

It remains a valuable therapy in CHF patients with AF.A

Hydralazine-isosorbide dinitrate combination should be reserved for patients who are truly intolerant of ACEIs and

angiotensin II receptor antagonists, or for whom these agents are contraindicated and no other therapeutic option exists.B

Fish oil (n-3 polyunsaturated fatty acids) should be considered as a second-line agent for patients with CHF who

remain symptomatic despite standard therapy which should include ACEIs or ARBs and beta-blockers if tolerated.B

Other agents

Amlodipine and felodipine can be used to treat comorbidities such as hypertension and CHD in patients with systolic

CHF. They have been shown to neither increase nor decrease mortality.B

Iron deficiency should be looked for and treated in CHF patients to improve symptoms, exercise tolerance and

quality of life.B