Heart Failure

Cholid Tri Tjahjono

Departemen Kardiologi dan Kedokteran
Vaskular
Fakultas Kedokteran Universitas Brawijaya
What is heart failure?
• Chronic Heart Failure (CHF):
– Heart failure is a complex syndrome in which
abnormal heart function results in, or increases
the subsequent risk of, clinical symptoms and
signs of low cardiac output and/or pulmonary or
systemic congestion.

• Acute Heart Failure Syndrome (AHF):

– “gradual or rapid change in heart failure signs and
symptoms resulting in the need for urgent therapy”

2012 CCS Management of heart failure guideline

 The burden of heart failure
NUMBER of PATIENTS ECONOMIC BURDEN
21 MILLION adults worldwide are In 2012, the overall worldwide cost
living with heart failure of heart failure was nearly $108
This number is expected to rise.1,2 BILLION.6

MORTALITY
50% of heart failure patients die
within 5 years from diagnosis.5

REHOSPITALISATION COMORBIDITIES: The vast majority

Heart failure is the NUMBER 1 cause of HF patients has 3 or more
of hospitalisation for patients aged comorbidities 3
>65 years.4

1. Mozaffarian D et al. Circulation. 2015;131(4):e29-e322.

2. Mosterd A et al. Heart. 2007;93(9):1137-1146.
3. http://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/Chronic-Conditions/Downloads/2012Chartbook.pdf
4. Cowie MR et al. Oxford PharmaGenesis; 2014. http://www.oxfordhealthpolicyforum.org/AHFreport. Accessed February 18, 2015.
5. Fauci AS et al. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008.
6. Cook C et al. Int J Cardiol. 2014;171(3):368-376.
 Definition of Heart Failure
Heart failure can be defined as an abnormality of cardiac structure or function leading to
failure of the heart to deliver oxygen at a rate commensurate with the requirements of
the metabolizing tissues, despite normal filling pressures (or only at the expense of
increased filling pressures).1

TERMINOLOGY used to describe HF2

Related to EF*: HFrEF (reduced ejection fraction: EF<40%)

HFmEF (mildly impaired EF: EF 40-49%
HFpEF (preserved ejection fraction: EF ≥50%)*
Related to time-course: New onset, transient, chronic
Related to progression: Acute, stable, worsening
Related to location: Left heart, right heart, combined

* There is no consensus concerning the cut-off for preserved EF 2

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

2. Dickstein K et al. Eur Heart J 2008;29:2388–442
 Aetiology of HF
VALVULAR HEART DISEASE MYOCARDIAL DISEASE
•Coronary artery disease
•Mitral
•Hypertension
•Aortic
•Cardiomyopathy
•Trisuspid
•Pulmonary
ENDOCARDIAL DISEASE
PERICARDIAL DISEASE •With/without hypereosinophilia
•Constrictive pericarditis •Endocardial fibroelastosis
•Pericardial effusion
ARRHYTHMIA
HIGH OUTPUT STATES •Tachyarrhythmia
•Anaemia •Atrial
•Sepsis •Ventricular
•Thyrotoxicosis •Bradyarrhythmia
•Paget‘s disease •Sinus node dysfunction
•Arteriovenous fistula CONDUCTION DISORDERS
•Atrioventricular block
VOLUME OVERLOAD
•Renal failure
•Iatrogenic (e.g. post-operative
CONGENITAL
fluid infusion HEART DISEASE McMurray et al. Eur Heart J 2012;33:1787–847
 Pathophysiology of HF
Injury to myocytes due
to myocardial infarction ELECTRICAL INSTABILITY
or other cause VENTRICULAR
REMODELING
REDUCTION of EF

NEUROHUMORAL
IMBALANCE

An imbalance occurs in three key neurohumoral systems:

•The renin–angiotensin–aldosterone system
•The sympathetic nervous system
•The natriuretic peptide system

The systemic responses in the renin–angiotensin–aldosterone and sympathetic nervous systems cause further
myocardial injury, and have detrimental effects on the blood vessels, and various organs, thereby creating a
pathophysiological ‘vicious cycle’. The natriuretic peptide system has a protective function, which can counterbalance
these detrimental effects.

1. McMurray JJ. N Engl J Med 2010;362:228–238

2. Shah AM. Lancet 2011;378:704–712
 Symptoms and signs of HF
The diagnosis of HF can be difficult, especially in the early stages

Symptoms Signs
Typical More specific

Breathlessness Elevated jugular venous pressure

Orthopnoea Hepatojugular reflux

Paroxysmal nocturnal dyspnoea Third heart sound (gallop rhythm)
Reduced exercise tolerance Laterally displaced apical impulse
Fatigue, tiredness, increased time
Cardiac murmur
to recover after exercise
Ankle swelling

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

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

 Definisi

Perki. 2015. Pedoman Tatalaksana Gagal Jantung Perki.

http://www.inaheart.org/upload/file/Pedoman_TataLaksana_Gagal_Jantung_2015.pdf
Perki. 2015. Pedoman Tatalaksana Gagal Jantung Perki.
http://www.inaheart.org/upload/file/Pedoman_TataLaksana_Gagal_Jantung_2015.pdf
Pathophysiology

Pathophysiology o heart disease : a

collaborative project o medical
students and aculty / editor, Leonard S.
Classification of Heart Failure

ACC/AHA stages of HF NYHA functional classification

(based on structure and damage to heart) (based on symptoms or physical activity)
Stage A At high risk for HF, but without structural or Class I No limitation of physical activity. Ordinary
functional abnormality physical activity does not cause undue fatigue,
No signs or symptoms palpitation or dyspnoea

Stage B Developed structural heart disease strongly Class II Slight limitation of physical activity. Comfortable
associated with development of HF, but at rest, but ordinary physical activity results in
without signs or symptoms HF symptoms

Stage C Symptomatic HF associated with underlying Class III Marked limitation of physical activity.
structural heart disease Comfortable at rest, but less than ordinary
activity results in HF symptoms

Stage D Advanced structural heart disease and Class IV Symptoms of HF present at rest. If any physical
marked symptoms of HF at rest, despite activity is undertaken, discomfort is increased
maximal medical therapy

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

Hunt et al. J Am Coll Cardiol 2009;53:e1–90
Natural history of HF
HF is a silently progressing disease
We begin to look at the disorder at the end of its natural history - that is too late!

The cardiovascular continuum

Vascular Remodeling

environmental
determinants

LVH
Diastolic
Diastolic Heart Failure
Dysfunction
physical CVD risk factors Disturbed
activity ↓ & biomarkers Microcirculation
Systolic Systolic
Dysfunction Heart Failure
CAD / Infarktion

genetic determinants

Myocardial Remodeling

Stage A B C/D

Krum, Gilbert. Lancet 2003;362:147–58

McMurray et al. Eur Heart J 2012;33:1787–847
The classic domains of HFrEF are
also present in HFpEF1
severely reduced exercise capacity, neuroendocrine activation, impaired quality
of life

Domains HFpEF HFrEF Controls

Peak VO2 14.2±0.5* 13.1±0.5* 19.9±0.7

Angiotensin 9.1±0.3* 8.7±0.3* 11.5±0.4

169±80
Norepinephrine 306±64* 287±62*

MLHFQ 24.8±4.4 43.8±3.9 -

*P<0.05 vs controls

HFpEF: HF despite absence of pump failure

Half of patients with HF have HFpEF2

1. Borlaug BA and Paulus WJ. Eur Heart J 2011;32: 670–679

2. Kitzman DW et al. JAMA 2002; ;288(17):2144-2150
 HFpEF is a major public health problem

HFpEF
stable angina & hypertension

hypertension

hypertension

hypertension
diabetes
hypertension
hypertension, very elderly
Outcomes of patients
with HFpEF as
Per 1000 patient years

compared with those

in trials of other
cardiovascular
disease, with similar
ages, sex and
comorbidities profiles

Campbell J Am Coll Cardiol 2012

 HFpEF is a major public health problem
HFpEF

Hypertension
hypertension

very elderly
Outcomes of patients
with HFpEF as
compared with those
in trials of other
Per 1000 patient years

cardiovascular
disease, with similar
ages, sex and
comorbidities profiles

Campbell J Am Coll Cardiol 2012

 HF has a detrimental effect on Quality of Life

Patients with HF commonly report psychological distress,

including:
• depression
• hostility and anxiety
• limitation in their activities of daily living
• disruption of work roles and social interaction with friends and
HF=heart failure; family
• reduced sexual activity and satisfaction

Grady. Crit Care Nurs Clin North Am 1993;5:661–70 2010

Heart failure definition

HFrEF and HFpEF

Systolic dysfunction Diastolic dysfunction

HFrEF HFmEF HFpEF

LVEF≤ 40% LVEF 40-49% LVEF ≥ 50%

Echocardiography is a useful method for evaluating left ventricular ejection fraction

HFpEF: heart failure with preserved ejection fraction, HFmEF : heart failure with mid-range ejection frection
Ponikowski et al. Eur Heart J 2016; 37(27): 2129-2200; McMurray et al. Eur Heart J 2012;33:1787–847;
Dickstein et al. Eur Heart J 2008;29:2388–442
21
Etiology

Most Common Causes of Heart Failure

• Coronary heart disease • Congenital heart disease
• Hypertension • Pericardial disease
• Valvular disease • Hyperkinetic states
• Cardiomyopathy • Anemia
 Idiopathic cardiomyopathy • Arterio-venous fistula
 Alcoholic cardiomyopathy • Beriberi
 Toxin-related cardiomyopathy e.g.
adriamycin
 Post-partum cardiomyopathy
 Hypertrophic obstructive
cardiomyopathy
 Tachyarrhythmia-induced
cardiomyopathy

• Infiltrative disorders (e.g.

amyloidosis)
*Others: Including hypertension, diabetes, exposure
to cardiotoxic agents, peripartum cardiomyopathy,
etc.
Krum and Gilbert. Lancet 2003;362:147–58; Colucci (Ed.). Atlas of Heart Failure, 5th ed. Springer 2008;
Dickstein et al. Eur Heart J 2008;29:2388–442
22
 The Pathophysiology of Chronic HF
Damage to cardiac myocytes and extracellular matrix leads to changes in
the size, shape and function of the heart (remodeling) and cardiac wall
stress

These changes lead to systemic neurohormonal imbalance

This may lead to fibrosis, apoptosis, hypertension, hypertrophy, cellular

and molecular alterations, myotoxicity

Remodeling and progressive Hemodynamic alterations, salt

worsening of LV function and water retention

Morbidity and mortality HF symptoms

arrhythmias, pump failure dyspnea, edema, fatigue

LV=left ventricular
McMurray. N Engl J Med 2010;362:228–38; Francis et al. Ann Intern Med 1984;101:370–7; Krum, Abraham. Lancet 2009;373:941–55
23
PATHOGENESIS OF HEART FAILURE
EVOLVING HEART FAILURE

25
CHRONIC HEART FAILURE : NEUROHORMONAL STATUS

DILATATION

CONSTRICTION

26
 New York Heart Association (NYHA)
Heart Failure Symptom Classification
NYHA CLASS LEVEL of IMPAIRMENT

I No Symptom Limitation With

Ordinary Physical Activity

Ordinary Physical Activity Somewhat

II Limited by Dyspnea (ie. Long distance

Walking, Climbing 2 flights of stairs)

III
Exercise Limited by Dyspnea at Mild Work
Loads (ie. Short Distance Walking,
Climbing One Flight of Stairs)

IV Dyspnea at Rest or
With Very Little Exertion
27
 ACC / AHA Classification of CHF
STAGE DESCRIPTION

A
High Risk For Hypertension, Diabetes Mellitus, CAD,
Developing Heart Family History of Cardiomyopathy
Failure

B Previous MI, LV Dysfunction,

Asymptomatic
Valvular Heart Disease
Heart Failure

C Structural Heart Disease, Dyspnea and

Symptomatic Fatigue, Impaired Exercise Tolerance
Heart Failure

D Marked Symptoms at Rest Despite

Refractory End-stage Maximal Medical Therapy
Heart Failure
28
 DETERMINANTS OF
VENTRICULAR FUNCTION

CONTRACTILITY

PRELOAD AFTERLOAD

STROKE
VOLUME

- Synergistic LV contraction HEART

- LV wall integrity RATE
- Valvular competence

CARDIAC OUTPUT
Comorbidities in HF
Comorbidities impact prognosis in patients with HF1,2

Why comorbidities are relevant in HF1:

•Comorbidities may affect the use of treatments
Gout for HF
Hyperlipidaemia •Drugs used to treat comorbidities may cause
COPD Iron deficiency worsening of HF
•Drugs used to treat HF and comorbidities may
Comorbidities in interact and reduce patient adherence
patients with HF •Most comorbidities are associated with worse
Depression
Hypertension Sleep disturbance clinical status and are predictors of poor
Angina Cancer prognosis in HF

Diabetes mellitus
Renal Anaemia
dysfunction Cachexia
Obesity

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

2. Ennezat et al. Nephrol Dial Transplant 2011;26:3908-13
The Pathophysiology of Heart Failure

Hurst. The Heart. Diagnosis and Management of Heart Failure.10th ed. 688
Section
Summary

Heart failure: Scope of the problem

• Heart failure can be defined as ‘an abnormality of cardiac structure or function leading to failure of the
heart to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissues,
despite normal filling pressures (or only at the expense of increased filling pressures)‘

• The global burden of HF is increasing in number and complexity, due to an aging patient population,
often with multiple comorbidities. Reducing readmissions can limit the burden for healthcare systems.

• There are many causes of HF that result in ventricular remodeling, reduction of the left ventricular
ejection fraction, and neurohumoral imbalance.

• Many of the symptoms of HF are non-specific. HF severity can be classified based on structure and
damage to heart (ACC/AHA) or based on symptoms or physical activity (NYHA). HF is a silently
progressive condition.

• HFrEF and HFpEF may present similarly within the clinical syndrome of HF. Half of patients have
HFpEF. Outcomes in HFpEF patients are worse than in similar patient populations with other
cardiovascular disease

• HF has a large impact on quality of life, including physical activities and psychological distress.
Comorbidities impact prognosis in patients with HF.

• HF places a significant physical and emotional burden on the caregiver.

Neurohormonal Activation

Activation of
RAS and ANS

Hurst. The Heart. Diagnosis and Management of Heart Failure.10th ed. 688
Principles of diagnosis of HF
All diagnostic steps are equally important

 Consider: Medical history, signs, symptoms

 Confirm: Natriuretic peptides, Echocardiography
 Assess clinical phenotype: HFrEF vs. HFpEF
 Assess etiology: Angiography, cMRI, Biopsy
 Risk stratification
 Workup for targeted therapies

Presented by BM Pieske during HF SUMMIT 2015

The diagnosis of HF is a staged process

Risk assessment at • Clinical assessment/Comorbidities

A preclinical stage • Biomarkers (Cardiac +EOD)
• Echocardiography
• Stress test
Initial diagnostic workup
in symptomatic patients

• Stress echocardiography
Detailed workup in case • Invasive tests & hemodynamics
B of uncertainity
• Cardiac MRI
• Comorbidities

• Cardiac MRI +++

Underlying patho- • Biopsy
C physiology & aetiology • Scintigraphy
• SPECT, Molecular imaging(?)

Presented by BM Pieske during HF SUMMIT 2015

Diagnosing HF
The diagnosis of HFpEF is more difficult than the diagnosis of HFrEF

The diagnosis of HFrEF requires three conditions to be satisfied

1. Symptoms typical of HF
2. Signs typical of HF
3. Reduced LVEF

The diagnosis of HFpEF requires four conditions to be satisfied

1. Symptoms typical of HF
2. Signs typical of HF
3. Normal or only mildly reduced LVEF and LV not dilated
4. Relevant structural heart disease (LV hypertrophy/LA enlargement)
and/or diastolic dysfunction

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

ESC HF diagnostic algorithm 2012
Acute onset Non-acute onset

ECG, Chest x-ray ECG, Possibly chest x-ray

Echocardiography BNP/NT-pro BNP* BNP/NT-pro BNP Echocardiography

ECG normal and ECG abnormal or ECG abnormal or ECG normal and
NT-proBNP < 300pg/mL NT-proBNP > NT-proBNP > 125 NT-proBNP <
or 300pg/mLbb or pg/mLaa or 125pg/mL or
BNP < 100 pg/mL BNP > 100 pg/mL bb BNP > 35 pg/mL aa BNP < 35 pg/mL

HF unlikely cc
HF unlikely cc
Echocardiography

If heart failure is confirmed by echocardiography,

determine aetiology and start appropriate treatment.

*In the acute setting, MR-proANP may also be used (cut-off point 120 pmol/L, i.e. <120 pmol/L = heart failure unlikely).
a.Exclusion cut-off points for natriuretic peptides are chosen to minimize the false-negative rate while reducing unnecessary referrals for echocardiography.
b.Other causes of elevated natriuretic peptide levels in the acute setting are an acute coronary syndrome, atrial or ventricular arrhythmias, pulmonary embolism, and severe chronic obstructive
pulmonary disease with elevated right heart pressures, renal failure, and sepsis. Other causes of an elevated natriuretic level in the non-acute setting are:
old age (>75 years), atrial arrhythmias, left ventricular hypertrophy, chronic obstructive pulmonary disease, and chronic kidney disease.
c. Treatment may reduce natriuretic peptide concentration, and natriuretic peptide concentrations may not be markedly elevated in patients with HF-PEF.

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

HFA/ESC diagnostic recommendations HFpEF
Symptoms or signs of HF

Normal or mildly reduced LV systolic function (LVEF >50% and LVEDVI <97 mL/m 2)

Evidence of abnormal LV relaxation, filling, diastolic distensibility, and diastolic stiffness

Invasive hemodynamic TD Biomarkers

measurements EIE′ >15 15 >EIE′ >8 NT-proBNP >220 pg/mL or BNP
mPCW >12 mmHg >200 pg/mL
or LVEDP >16 mmHg
or  >48 ms
or b >0.27
Biomarkers TD
Echo – blood flow Doppler
NT-proBNP EIA>50 yr <0.5 and DT>50 yr >280 ms EIE′ >8
>220 pg/mL or or Ard–Ad >30 ms
BNP >200 pg/mL or LAVI >40 mL/m2
or LVMI >122 g/m2(♀); >149 g/m2 (♂) or
atrial fibrillation

HFpEF
Paulus et al. Eur Heart J 2007;28:2539–50
Particular relevance of BNP
• diagnosis
• staging
• risk stratification
• monitor/titrate therapy
• admission/discharge decisions:
> rule out symptomatic LV dysfunction

A normal natriuretic peptide level in an untreated patient virtually

excludes significant cardiac disease
Consider different cut-off values in various clinical situations

Presented by K Dickstein during HF SUMMIT 2015

Section
Summary

Diagnosis of HF
• Adequate diagnosis of HF includes screening for cardiac dysfunction in
patients at risk, confirming the clinical suspicion with objective diagnostic
measures, and identifying the underlying phenotype and aetiology.

• The HF diagnosis should be considered at all levels of care, to guide

management decisions.

• The diagnosis of HFpEF is more difficult than the diagnosis of HFrEF because
it is largely one of exclusion.

• Measuring natriuretic peptide levels can help diagnosis. A normal natriuretic

peptide level in an untreated patient virtually excludes significant cardiac
disease, making an echocardiogram unnecessary.
There are many treatment objectives for chronic HF

Objectives of treatment for chronic HF

1. Prognosis • reduce mortality
2. Morbidity • relieve symptoms and signs
• improve QoL
• eliminate edema and fluid retention
• increase exercise capacity
• reduce fatigue and breathlessness
• reduce the need for hospitalization
• provide end of life care

3. Prevention • occurrence of myocardial damage

• progression of myocardial damage
• remodelling of the myocardium
• reoccurrence of symptoms and fluid
accumulation
• hospitalization

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

McMurray et al. Eur Heart J 2012;33:1787–847
ACC/AHA Guidelines recommend incremental
addition of treatments as HF progresses

Therapy
Therapy goals Therapy
Therapy goals Therapy
Therapy goals Therapy
goals goals goals Therapy goalsgoals
 Treat  All  All
Treat hypertension
hypertension All measures
measures under
under All measures
measures under
under Stages
Stages A
A  Appropriate
Appropriate measures
measures
 Encourage Stage
Stage A and
and B
Encourage smoking
smoking cessation
cessation A B under
under Stages
Stages A,
A, B,
B, C
C

Refractory symptoms of HF at rest

 Dietary salt restriction
 Treat
Treat lipid
lipid disorders
disorders

Development of symptoms of HF
Dietary salt restriction
 Encourage
Drugs
Drugs  Decision re: appropriate
Decision re: appropriate
Encourage regular
regular exercise
exercise  ACEIs
ACEIs or
or ARBs
ARBs in
in appropriate
appropriate Drugs
Drugs for for routine
routine useuse level
level of
of care
care
Structural heart disease

 Discourage
Discourage alcohol
alcohol intake, patients  Diuretics
illicit drug use
intake, patients Diuretics for
for fluid
fluid retention
retention
illicit drug use  β-blockers in appropriate  ACEIs Options
Options
β-blockers in appropriate ACEIs
 Control
Control metabolic
metabolic syndrome
syndrome patients
patients  β-blockers
β-blockers  Compassionate
Compassionate end-of-life
end-of-life
Drugs Devices care/hospice
care/hospice
Drugs Devices inin selected
selected patients
patients Drugs
Drugs in in selected
selected patients
patients
 ACEIs
ACEIs or
or ARBs
ARBs inin appropriate
appropriate  Implantable
Implantable defibrillators
defibrillators  Aldosterone
Aldosterone antagonists  Extraordinary
Extraordinary measures
measures
patients antagonists
patients for
for vascular
vascular disease
disease or
or  ARBs  Heart
Heart transplant
transplant
diabetes ARBs
diabetes  Chronic
 Digitalis
Digitalis Chronic inotropes
inotropes
 Hydralazine/nitrates
Hydralazine/nitrates  Permanent
Permanent mechanical
mechanical
Devices support
support
Devices inin selected
selected patients
patients
 Biventricular  Experimental
Experimental surgery
surgery or
Biventricular pacing
pacing or
 Implantable
Implantable defibrillators
defibrillators drugs
drugs

Hunt et al. J Am Coll Cardiol 2009;53:e1–90

HFpEF and HFrEF respond differently to
pharmacological treatment options

Treatment option HFpEF HFrEF

Diuretics YES YES

CCBs YES NO

Beta-blockers NO YES

ACEIs NO YES

ARBs NO YES

MR antagonists NO YES

Ivabradine NO YES

Digoxin NO YES
H-ISDN NO YES
ARNIs PARAGON-HF study YES

Raina A and Kanwar M. Curr Heart Fail Rep. 2014: 11(4):374-81

Tschöpe C and Lam CS. Herz 2012: 37(8):875-9
Treatment options for chronic HF
ESC Guidelines 2012
Chronic symptomatic systolic HF (NYHA II-IV) – Step 1
Diuretics to relieve symptoms/signs of congestion
+
ACE inhibitor (or ARB if not tolerated)

ADD a beta-blocker

Still NYHA class

II-IV?
YES NO

No further specific treatment

ADD an MR antagonist Continue in disease-management
programme

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

Treatment options for chronic HF
ESC Guidelines 2012
Chronic symptomatic systolic HF (NYHA II-IV) – Step 2
Still NYHA class II-IV?

YES NO

LVEF ≤ 35% ?

YES NO

SR and HR ≥ 70
beats/min ? NO
No further specific treatment
Continue in disease-management
YES
programme
ADD ivabradine

Still NYHA class II-IV

and LVEF ≤ 35% ?

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

Treatment options for chronic HF
ESC Guidelines 2012
Chronic symptomatic systolic HF (NYHA II-IV) – Step 3
Still NYHA class II-IV and LVEF
≤35% ?

YES NO

QRS duration ≥120 ms?

YES NO

Consider CRT-P/CRT-D Consider ICD

No further specific treatment
NO Continue in disease-management
Stil NYHA class II-IV? programme

YES
Consider digoxin and/or H-ISDN
If end stage, consider LVAD and/or transplantation

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

Adding therapies is adding life
24 month mortality

NUMBER of THERAPIES ODDS RATIO

(vs 0 or 1 therapy) (95% confidence interval)

2 therapies 0.63 (0.47-0.85) p=0.0026

3 therapies 0.38 (0.29-0.51) p<0.0001
4 therapies 0.30 (0.23-0.41) p<0.0001
5, 6, or 7 therapies 0.31 (0.23-0.42) p<0.0001
0 0.5 1 1.5 2

This study examined the individual and incremental clinical effectiveness of guideline-recommended therapies for patients with HF and reduced
LVEF.
ORs for 24-month mortality associated with the number of guideline-recommended therapies received at baseline.
Analysis includes all patients from the case-control population (N=4128). The number (%) of patients receiving each number of therapies at
baseline was as follows: 0 or 1, 238 (5.8%); 2, 712 (17.3%); 3, 1327 (32.2%); 4, 1123 (27.2%); and 5, 6, or 7, 728 (17.6%).

Fonarow GC et al. J Am Heart Assoc 2012;1:16-26

Adding therapies is adding life
Beta- Beta- Beta- Beta- Beta-blocker + Beta-blocker +
blocker blocker + blocker + blocker + ACEI/ARB + ACEI/ARB + ICD
Change in Odds of 24-Month Mortality (%)

ACEI/ARB ACEI/AR ACEI/ARB ICD + HF + HF education

B + ICD + ICD + HF education + +
education anticoagulation anticoagulation
for AF for AF + CRT

(-28% to -49%) (-54% to -71%) (-68% to -81%) (-75% to -86%) (-77% to -88%) (-72% to -87%)
P<0.0001 P<0.0001 P<0.0001 P=0.0038 P=0.1388 P=0.1208

Fonarow GC et al. J Am Heart Assoc 2012;1:16-26

Treatment options for HFpEF
Improving signs & symptoms

To control sodium and water retention

Diuretics
Diuretics To relieve breathlessness and oedema

To improve exercise capacity

CCBs
CCBs
To control ventricular rate in AF
To treat hypertension and myocardial ischaemia

Management
Management Adequate treatment of hypertension
of
ofunderlying
underlying Adequate treatment of myocardial ischaemia
disease
disease
McMurray et al. Eur Heart J 2012;33:1787–847

HEART FAILURE SUMMIT 2016, BARCELONA

Treatment options for HFpEF
Improving prognosis
‘No treatment has yet been shown, convincingly, to reduce morbidity and
mortality in patients with HFpEF.’ (ESC Guidelines 2012)
#
STUDY Study drug Endpoint Outcome Publication
Patients
Yusuf S et al
CHARM- CV death or HF
Candesartan 3023 Lancet 2003
Preserved hospitalization
Primary
Cleland JG et al
Death or HF end-point
PEP-CHF Perindopril 850 Eur Heart J 2006
hospitalization not met

Death or HF Massie BN et al NEJM

I-Preserve Irbesartan 4128 hospitalization 2008

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

Yusuf S et al. Lancet 2003;362:777
Cleland JG et al. Eur Heart J 2006;27:2338
Massie BM et al. NEJM 2008;359:2456
Holistic management of HF
ESC Guidelines 2012
Management programmes for patients with HFrEF & HFpEF
Characteristics
• Should employ a multidisciplinary approach
• Should target high-risk symptomatic patients
• Should include competent and professionally educated staff

Components
• Optimized medical and device management
• Adequate patient education, with special emphasis on adherence and self-care
• Patient involvement in symptom monitoring and flexible diuretic use
• Follow-up after discharge
• Increased access to healthcare
• Facilitated access to care during episodes of decompensation
• Assessment of (and appropriate intervention in response to) an unexplained increase in
weight, nutritional status, functional status, quality of life, and laboratory findings
• Access to advanced treatment options
• Provision of psychosocial support to patients and family and/or caregivers McMurray et al. Eur Heart J 2012;33:1787–847

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

ESC recommendations
for exercise prescription and multidisciplinary management

RECOMMENDATIONS CLASS LEVEL • Services, such as cardiac rehabilitation

It is recommended that regular
aerobic exercise is encouraged
in patients with heart failure to
improve functional capacity and
symptoms
It is recommended that patients
with heart failure are enrolled in a
multidisciplinary care
management programme to
reduce the risk of heart failure
hospitalization
and palliative care, must be integrated
I A into the overall provision for patients
with HF
• Multidisciplinary management
programmes are vital, designed to
improve outcomes through structured
follow-up with patient education,
I A optimization of medical treatment,
psychosocial support, and improved
access to care.

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

Personalised medicine in HF
Personalisation for patients with HF will surely improve in
the future, but also today one does not fit all
Personalisation by traditional biomarkers:
• Echo
• ECG
• Blood Pressure
• Laboratory examinations (renal function, electrolytes, hemoglobin, glycemia)

Other more recent biomarkers

How can we improve the personalisation of treatment in the future
• Genetics
• Pharmacogenomics
• Gene therapy

Presented by A. Maggioni during HF SUMMIT 2015

Section
Summary

Summary: HF Guidelines
• ACE-inhibitors, beta-blockers and mineralocorticoid receptor antagonists
form the cornerstone of HF therapy, given their mortality benefit. Incremental
addition of treatments is recommended as HF progresses: Adding therapies
is adding life.

• HFrEF and HFpEF differently respond to treatment. Treatment in HFpEF is

aimed to improve signs and symptoms, as no treatment has yet been shown
to improve prognosis in HFpEF.

• HF care is already somewhat personalised, since management is guided by

traditional biomarkers (echo, ECG, blood pressure, laboratory examinations).
In the future, genetics, pharmacogenomics and gene therapy may yield more
targeted treatment strategies.

• The ESC guidelines also recommend regular aerobic exercise and enrolment
in care-management programmes.
Recommendations therapy for HF
stage B

Yance, SW, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of
the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J
Am Coll Cardiol 2013;62:1495–539.
Yance, SW, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College
Yance, SW, et al. 2013 ACCF/AHA guideline for t
management of heart failure: executive summa
report of the American College of Cardiology
Foundation/American Heart Association Task Fo
on Practice Guidelines. J Am Coll Cardiol
2013;62:1495–539.
Yance, SW, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the
American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll
Cardiol 2013;62:1495–539.
Acute Heart Failure