Acute Heart Failure Esc PDF
Acute Heart Failure Esc PDF
Acute Heart Failure Esc PDF
doi:10.1093/eurheartj/ehw128
* Corresponding authors: Piotr Ponikowski, Department of Heart Diseases, Wroclaw Medical University, Centre for Heart Diseases, Military Hospital, ul. Weigla 5, 50-981 Wroclaw,
Poland, Tel: +48 261 660 279, Tel/Fax: +48 261 660 237, E-mail: piotrponikowski@4wsk.pl.
Adriaan Voors, Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands, Tel: +31 50 3612355,
Fax: +31 50 3614391, E-mail: a.a.voors@umcg.nl.
ESC Committee for Practice Guidelines (CPG) and National Cardiac Societies document reviewers: listed in the Appendix.
ESC entities having participated in the development of this document:
Associations: Acute Cardiovascular Care Association (ACCA), European Association for Cardiovascular Prevention and Rehabilitation (EACPR), European Association of
Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA).
Councils: Council on Cardiovascular Nursing and Allied Professions, Council for Cardiology Practice, Council on Cardiovascular Primary Care, Council on Hypertension.
Working Groups: Cardiovascular Pharmacotherapy, Cardiovascular Surgery, Myocardial and Pericardial Diseases, Myocardial Function, Pulmonary Circulation and Right Ventricular
Function, Valvular Heart Disease.
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Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford
University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC (journals.permissions@oup.com).
Disclaimer. The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at
the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recom-
mendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encour-
aged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or
therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and
accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor
do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent
public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the
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The article has been co-published with permission in European Heart Journal and European Journal of Heart Failure. All rights reserved in respect of European Heart Journal.
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2130 ESC Guidelines
Maxime Guenoun (France), Gerd Hasenfuss (Germany), Gerhard Hindricks (Germany), Arno W. Hoes
(The Netherlands), Bernard Iung (France), Tiny Jaarsma (Sweden), Paulus Kirchhof (UK/Germany), Juhani Knuuti
(Finland), Philippe Kolh (Belgium), Stavros Konstantinides (Germany/Greece), Mitja Lainscak (Slovenia),
Patrizio Lancellotti (Belgium), Gregory Y. H. Lip (UK), Francesco Maisano (Switzerland), Christian Mueller
(Switzerland), Mark C. Petrie (UK), Massimo F. Piepoli (Italy), Silvia G. Priori (Italy), Adam Torbicki (Poland),
Hiroyuki Tsutsui (Japan), Dirk J. van Veldhuisen (The Netherlands), Stephan Windecker (Switzerland), Clyde Yancy
(USA), Jose Luis Zamorano (Spain)
The disclosure forms of all experts involved in the development of these guidelines are available on the ESC website
http://www.escardio.org/guidelines.
Online publish-ahead-of-print 20 May 2016
Table of Contents
Abbreviations and acronyms . . . . . . . . . . . . . . . . . . . . . . . .2131 5.9 Cardiac computed tomography . . . . . . . . . . . . . . . . .2144
1. Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2134 5.10 Other diagnostic tests . . . . . . . . . . . . . . . . . . . . . .2145
2. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2136 5.10.1 Genetic testing in heart failure . . . . . . . . . . . . . .2145
3. Definition, epidemiology and prognosis . . . . . . . . . . . . . . .2136 6. Delaying or preventing the development of overt heart
3.1 Definition of heart failure . . . . . . . . . . . . . . . . . . . . .2136 failure or preventing death before the onset of symptoms . . . . .2146
3.2 Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2137 7. Pharmacological treatment of heart failure with reduced
3.2.1 Heart failure with preserved, mid-range and reduced ejection fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2147
ejection fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . .2137 7.1 Objectives in the management of heart failure . . . . . . .2147
3.2.2 Terminology related to the time course of heart 7.2 Treatments recommended in all symptomatic patients
failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2137 with heart failure with reduced ejection fraction . . . . . . . . .2148
3.2.3 Terminology related to the symptomatic severity 7.2.1 Angiotensin-converting enzyme inhibitors . . . . . . .2148
of heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2138 7.2.2 Beta-blockers . . . . . . . . . . . . . . . . . . . . . . . . . .2148
3.3 Epidemiology, aetiology and natural history of heart failure 2138 7.2.3 Mineralocorticoid/aldosterone receptor antagonists .2148
3.4 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2138 7.3 Other treatments recommended in selected symptomatic
4. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2138 patients with heart failure with reduced ejection fraction . . .2148
4.1 Symptoms and signs . . . . . . . . . . . . . . . . . . . . . . . .2138 7.3.1 Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2148
4.2 Essential initial investigations: natriuretic peptides, 7.3.2 Angiotensin receptor neprilysin inhibitor . . . . . . . .2151
electrocardiogram, and echocardiography . . . . . . . . . . . . .2139 7.3.3 If - channel inhibitor . . . . . . . . . . . . . . . . . . . . . .2152
4.3 Algorithm for the diagnosis of heart failure . . . . . . . . .2140 7.3.4 Angiotensin II type I receptor blockers . . . . . . . . .2152
4.3.1 Algorithm for the diagnosis of heart failure in the 7.3.5 Combination of hydralazine and isosorbide
non-acute setting . . . . . . . . . . . . . . . . . . . . . . . . . . .2140 dinitrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2152
4.3.2 Diagnosis of heart failure with preserved ejection 7.4 Other treatments with less certain benefits in
fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2140 symptomatic patients with heart failure with reduced ejection
5. Cardiac imaging and other diagnostic tests . . . . . . . . . . . . .2142 fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2152
5.1 Chest X-ray . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2142 7.4.1 Digoxin and other digitalis glycosides . . . . . . . . . .2152
5.2 Transthoracic echocardiography . . . . . . . . . . . . . . . .2142 7.4.2 n-3 polyunsaturated fatty acids . . . . . . . . . . . . . .2153
5.2.1 Assessment of left ventricular systolic function . . . .2142 7.5 Treatments not recommended (unproven benefit) in
5.2.2 Assessment of left ventricular diastolic function . . .2143 symptomatic patients with heart failure with reduced ejection
5.2.3 Assessment of right ventricular function and fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2153
pulmonary arterial pressure . . . . . . . . . . . . . . . . . . . .2143 7.5.1 3-Hydroxy-3-methylglutaryl-coenzyme A reductase
5.3 Transoesophageal echocardiography . . . . . . . . . . . . .2143 inhibitors (‘statins’) . . . . . . . . . . . . . . . . . . . . . . . . . .2153
5.4 Stress echocardiography . . . . . . . . . . . . . . . . . . . . .2143 7.5.2 Oral anticoagulants and antiplatelet therapy . . . . . .2153
5.5 Cardiac magnetic resonance . . . . . . . . . . . . . . . . . . .2143 7.5.3 Renin inhibitors . . . . . . . . . . . . . . . . . . . . . . . .2153
5.6 Single-photon emission computed tomography and 7.6 Treatments not recommended (believed to cause harm)
radionuclide ventriculography . . . . . . . . . . . . . . . . . . . . .2143 in symptomatic patients with heart failure with reduced
5.7 Positron emission tomography . . . . . . . . . . . . . . . . .2143 ejection fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2154
5.8 Coronary angiography . . . . . . . . . . . . . . . . . . . . . . .2144 7.6.1 Calcium-channel blockers . . . . . . . . . . . . . . . . . .2154
ESC Guidelines 2131
8. Non-surgical device treatment of heart failure with reduced 12. Acute heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . .2171
ejection fraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2154 12.1 Definition and classification . . . . . . . . . . . . . . . . . . .2171
8.1 Implantable cardioverter-defibrillator . . . . . . . . . . . . .2154 12.2 Diagnosis and initial prognostic evaluation . . . . . . . . .2172
8.1.1 Secondary prevention of sudden cardiac death . . . .2154 12.3 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . .2176
8.1.2 Primary prevention of sudden cardiac death . . . . . .2155 12.3.1 Identification of precipitants/causes leading to
8.2 Cardiac resynchronization therapy . . . . . . . . . . . . . . .2156 decompensation that needs urgent management . . . . . . .2176
8.3 Other implantable electrical devices . . . . . . . . . . . . . .2157 12.3.2 Criteria for hospitalization in ward vs intensive
9. Treatment of heart failure with preserved ejection fraction . .2157 care/coronary care unit . . . . . . . . . . . . . . . . . . . . . . .2177
9.1 Effect of treatment on symptoms in heart failure with 12.3.3 Management of the early phase . . . . . . . . . . . . .2177
preserved ejection fraction . . . . . . . . . . . . . . . . . . . . . . .2158 12.3.4 Management of patients with cardiogenic shock . .2182
9.2 Effect of treatment on hospitalization for heart failure in 12.4 Management of evidence-based oral therapies . . . . . .2182
AMI acute myocardial infarction CHARM-Preserved Candesartan Cilexetil in Heart Failure Assess-
AMICA Atrial fibrillation Management In Congestive ment of Reduction in Mortality and Morbidity
heart failure with Ablation CI cardiac index
ANP A-type natriuretic peptide CI-AKI contrast-induced acute kidney injury
ANS autonomic nervous system CIBIS II Cardiac Insufficiency Bisoprolol Study II
ARB angiotensin receptor blocker CK creatine kinase
ARNI angiotensin receptor neprilysin inhibitor CKD chronic kidney disease
ARVC arrhythmogenic right ventricular CK-MB creatine kinase MB
cardiomyopathy CMP cardiomyopathy
AST aspartate aminotransferase CMR cardiac magnetic resonance
ASV assisted servo-ventilation COMPANION Comparison of Medical Therapy, Pacing, and
A great number of Guidelines have been issued in recent years by panels. The Committee is also responsible for the endorsement pro-
the European Society of Cardiology (ESC) as well as by other soci- cess of these Guidelines. The ESC Guidelines undergo extensive re-
eties and organisations. Because of the impact on clinical practice, view by the CPG and external experts. After appropriate revisions
quality criteria for the development of guidelines have been estab- the Guidelines are approved by all the experts involved in the Task
lished in order to make all decisions transparent to the user. The re- Force. The finalized document is approved by the CPG for publica-
commendations for formulating and issuing ESC Guidelines can be tion in the European Heart Journal. The Guidelines were developed
found on the ESC website (http://www.escardio.org/Guidelines- after careful consideration of the scientific and medical knowledge
&-Education/Clinical-Practice-Guidelines/Guidelines-development/ and the evidence available at the time of their dating.
Writing-ESC-Guidelines). ESC Guidelines represent the official pos- The task of developing ESC Guidelines covers not only integration
ition of the ESC on a given topic and are regularly updated. of the most recent research, but also the creation of educational tools
Members of this Task Force were selected by the ESC to re- and implementation programmes for the recommendations. To im-
it has been shown that the outcome of disease may be favourably in- (viii) a new algorithm for a combined diagnosis and treatment ap-
fluenced by the thorough application of clinical recommendations. proach of acute HF based on the presence/absence of conges-
Surveys and registries are needed to verify that real-life daily prac- tion/hypoperfusion.
tice is in keeping with what is recommended in the guidelines, thus
We followed the format of the previous ESC 2012 HF Guidelines.
completing the loop between clinical research, writing of guidelines,
Therapeutic recommendations state the treatment effect supported
disseminating them and implementing them into clinical practice.
by the class and level of recommendation in tabular format; in the
Health professionals are encouraged to take the ESC Guidelines
case of chronic HF due to left ventricular systolic dysfunction
fully into account when exercising their clinical judgment, as well as
(LVSD) the recommendations focus on mortality and morbidity
in the determination and the implementation of preventive, diagnos-
outcomes. Detailed summaries of the key evidence supporting gen-
tic or therapeutic medical strategies. However, the ESC Guidelines
erally recommended treatments have been provided. For diagnostic
do not override in any way whatsoever the individual responsibility
recommendations a level of evidence C has been typically decided
conduction can also cause HF (and more than one abnormality is of- characteristics, pathophysiology and treatment of this group of pa-
ten present). Identification of the underlying cardiac problem is cru- tients. Patients with HFmrEF most probably have primarily mild sys-
cial for therapeutic reasons, as the precise pathology determines the tolic dysfunction, but with features of diastolic dysfunction
specific treatment used (e.g. valve repair or replacement for valvular (Table 3.1).
disease, specific pharmacological therapy for HF with reduced EF, Patients without detectable LV myocardial disease may have
reduction of heart rate in tachycardiomyopathy, etc). other cardiovascular causes for HF (e.g. pulmonary hypertension,
valvular heart disease, etc.). Patients with non-cardiovascular path-
ologies (e.g. anaemia, pulmonary, renal or hepatic disease) may have
3.2 Terminology
symptoms similar or identical to those of HF and each may compli-
3.2.1 Heart failure with preserved, mid-range and reduced
cate or exacerbate the HF syndrome.
ejection fraction
The main terminology used to describe HF is historical and is based
Table 3.1 Definition of heart failure with preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction
(HFrEF)
BNP ¼ B-type natriuretic peptide; HF ¼ heart failure; HFmrEF ¼ heart failure with mid-range ejection fraction; HFpEF ¼ heart failure with preserved ejection fraction; HFrEF ¼
heart failure with reduced ejection fraction; LAE ¼ left atrial enlargement; LVEF ¼ left ventricular ejection fraction; LVH ¼ left ventricular hypertrophy; NT-proBNP ¼ N-terminal
pro-B type natriuretic peptide.
a
Signs may not be present in the early stages of HF (especially in HFpEF) and in patients treated with diuretics.
b
BNP.35 pg/ml and/or NT-proBNP.125 pg/mL.
2138 ESC Guidelines
(MRA), ivabradine and/or CRT]. ‘Congestive HF’ is a term that is In clinical practice, a clear distinction between acquired and inher-
sometimes used, and may describe acute or chronic HF with evi- ited cardiomyopathies remains challenging. In most patients with a
dence of volume overload. Many or all of these terms may be accur- definite clinical diagnosis of HF, there is no confirmatory role for
ately applied to the same patient at different times, depending upon routine genetic testing, but genetic counselling is recommended in
their stage of illness. patients with hypertrophic cardiomyopathy (HCM), ‘idiopathic’
DCM or arrhythmogenic right ventricular cardiomyopathy
3.2.3 Terminology related to the symptomatic severity (ARVC) (see Section 5.10.1), since the outcomes of these tests
of heart failure may have clinical implications.
The NYHA functional classification (Web Table 3.2) has been used Over the last 30 years, improvements in treatments and their im-
to describe the severity of symptoms and exercise intolerance. plementation have improved survival and reduced the hospitalization
However, symptom severity correlates poorly with many measures rate in patients with HFrEF, although the outcome often remains un-
3.4 Prognosis
3.3 Epidemiology, aetiology and natural Estimation of prognosis for morbidity, disability and death helps pa-
history of heart failure tients, their families and clinicians decide on the appropriate type
and timing of therapies (in particular, decisions about a rapid transi-
The prevalence of HF depends on the definition applied, but is ap-
tion to advanced therapies) and assists with planning of health and
proximately 1–2% of the adult population in developed countries,
social services and resources.
rising to ≥10% among people .70 years of age.14 – 17 Among peo-
Numerous prognostic markers of death and/or HF hospitalization
ple .65 years of age presenting to primary care with breathlessness
have been identified in patients with HF (Web Table 3.5). However,
on exertion, one in six will have unrecognized HF (mainly
their clinical applicability is limited and precise risk stratification in
HFpEF).18,19 The lifetime risk of HF at age 55 years is 33% for
HF remains challenging.
men and 28% for women.16 The proportion of patients with HFpEF
In recent decades, several multivariable prognostic risk scores
ranges from 22 to 73%, depending on the definition applied, the clin-
have been developed for different populations of patients with
ical setting (primary care, hospital clinic, hospital admission), age and
HF,36 – 41 and some are available as interactive online applications.
sex of the studied population, previous myocardial infarction and
Multivariable risk scores may help predict death in patients with
the year of publication.17,18,20 – 30
HF, but remain less useful for the prediction of subsequent HF hos-
Data on temporal trends based on hospitalized patients suggest
pitalizations.37,38 A systematic review examining 64 prognostic
that the incidence of HF may be decreasing, more for HFrEF than
models37 along with a meta-analysis and meta-regression study of
for HFpEF.31,32 HFpEF and HFrEF seem to have different epidemio-
117 prognostic models38 revealed only a moderate accuracy of
logical and aetiological profiles. Compared with HFrEF, patients
models predicting mortality, whereas models designed to predict
with HFpEF are older, more often women and more commonly
the combined endpoint of death or hospitalization, or only hospital-
have a history of hypertension and atrial fibrillation (AF), while a his-
ization, had an even poorer discriminative ability.
tory of myocardial infarction is less common.32,33 The characteristics
of patients with HFmrEF are between those with HFrEF and HFpEF,34
but further studies are needed to better characterize this population. 4. Diagnosis
The aetiology of HF is diverse within and among world regions.
There is no agreed single classification system for the causes of 4.1 Symptoms and signs
HF, with much overlap between potential categories (Table 3.4). Symptoms are often non-specific and do not, therefore, help discrim-
Many patients will have several different pathologies—cardiovascu- inate between HF and other problems (Table 4.1).42 – 46 Symptoms and
lar and non-cardiovascular—that conspire to cause HF. Identifica- signs of HF due to fluid retention may resolve quickly with diuretic
tion of these diverse pathologies should be part of the diagnostic therapy. Signs, such as elevated jugular venous pressure and displace-
workup, as they may offer specific therapeutic opportunities. ment of the apical impulse, may be more specific, but are harder to
Many patients with HF and ischaemic heart disease (IHD) have a detect and have poor reproducibility.18,46,47 Symptoms and signs
history of myocardial infarction or revascularization. However, a may be particularly difficult to identify and interpret in obese indivi-
normal coronary angiogram does not exclude myocardial scar duals, in the elderly and in patients with chronic lung disease.48 – 50
(e.g. by CMR imaging) or impaired coronary microcirculation as al- Younger patients with HF often have a different aetiology, clinical pres-
ternative evidence for IHD. entation and outcome compared with older patients.51,52
ESC Guidelines 2139
DISEASED MYOCARDIUM
Ischaemic heart Myocardial scar
disease
Myocardial stunning/hibernation
Epicardial coronary artery disease
Abnormal coronary microcirculation
Endothelial dysfunction
Toxic damage Recreational substance abuse Alcohol, cocaine, amphetamine, anabolic steroids.
Heavy metals Copper, iron, lead, cobalt.
Radiation
Immune-mediated Related to infection Bacteria, spirochaetes, fungi, protozoa, parasites (Chagas disease), rickettsiae, viruses (HIV/AIDS).
Not related to infection Lymphocytic/giant cell myocarditis, autoimmune diseases (e.g. Graves’ disease, rheumatoid
damage
arthritis, connective tissue disorders, mainly systemic lupus erythematosus), hypersensitivity and
eosinophilic myocarditis (Churg–Strauss).
Related to malignancy
Not related to malignancy Amyloidosis, sarcoidosis, haemochromatosis (iron), glycogen storage diseases (e.g. Pompe disease),
lysosomal storage diseases (e.g. Fabry disease).
Metabolic Hormonal
derangements disease, Addison disease, diabetes, metabolic syndrome, phaeochromocytoma, pathologies related
to pregnancy and peripartum.
Nutritional
(e.g. malignancy, AIDS, anorexia nervosa), obesity.
Genetic abnormalities Diverse forms HCM, DCM, LV non-compaction, ARVC, restrictive cardiomyopathy (for details see respective
expert documents), muscular dystrophies and laminopathies.
ABNORMAL LOADING CONDITIONS
Hypertension
Valve and Acquired Mitral, aortic, tricuspid and pulmonary valve diseases.
myocardium
Congenital Atrial and ventricular septum defects and others (for details see a respective expert document).
structural defects
Pericardial and Pericardial Constrictive pericarditis
endomyocardial Pericardial effusion
pathologies
Endomyocardial
High output states
Volume overload
ARRHYTHMIAS
Tachyarrhythmias Atrial, ventricular arrhythmias.
Bradyarrhythmias Sinus node dysfunctions, conduction disorders.
ARVC ¼ arrhythmogenic right ventricular cardiomyopathy; DCM ¼ dilated cardiomyopathy; EMF ¼ endomyocardial fibrosis; GH ¼ growth hormone; HCM ¼ hypertrophic
cardiomyopathy; HES ¼ hypereosinophilic syndrome; HIV/AIDS ¼ human immunodeficiency virus/acquired immune deficiency syndrome; LV ¼ left ventricular.
A detailed history should always be obtained. HF is unusual in an 4.2 Essential initial investigations:
individual with no relevant medical history (e.g. a potential cause of natriuretic peptides, electrocardiogram
cardiac damage), whereas certain features, particularly previous
myocardial infarction, greatly increase the likelihood of HF in a pa-
and echocardiography
tient with appropriate symptoms and signs.42 – 45 The plasma concentration of natriuretic peptides (NPs) can be used
At each visit, symptoms and signs of HF need to be assessed, with as an initial diagnostic test, especially in the non-acute setting when
particular attention to evidence of congestion. Symptoms and signs echocardiography is not immediately available. Elevated NPs help
are important in monitoring a patient’s response to treatment and establish an initial working diagnosis, identifying those who require
stability over time. Persistence of symptoms despite treatment usu- further cardiac investigation; patients with values below the cut-
ally indicates the need for additional therapy, and worsening of point for the exclusion of important cardiac dysfunction do not
symptoms is a serious development (placing the patient at risk of ur- require echocardiography (see also Section 4.3 and Section 12).
gent hospital admission and death) and merits prompt medical Patients with normal plasma NP concentrations are unlikely to
attention. have HF. The upper limit of normal in the non-acute setting for
2140 ESC Guidelines
Figure 4.1 Diagnostic algorithm for a diagnosis of heart failure of non-acute onset
BNP ¼ B-type natriuretic peptide; CAD ¼ coronary artery disease; HF ¼ heart failure; MI ¼ myocardial infarction; NT-proBNP ¼ N-terminal
pro-B type natriuretic peptide.
a
Patient reporting symptoms typical of HF (see Table 4.1).
b
Normal ventricular and atrial volumes and function.
c
Consider other causes of elevated natriuretic peptides (Table 12.3).
2142 ESC Guidelines
† In case of uncertainty, a stress test or invasively measured ele- Patients with HFpEF are a heterogeneous group with various
vated LV filling pressure may be needed to confirm the diagnosis underlying aetiologies and pathophysiological abnormalities. Based
(for details, see below). on specific suspected causes, additional tests can be performed
(Web Table 4.4).71,88 – 94 However, they can only be recommended
The initial assessment consists of a clinical diagnosis compatible with if the results might affect management.
the algorithm presented above and the assessment of LVEF by echo-
cardiography. The cut-off of 50% for a diagnosis of HFpEF is arbi-
trary; patients with an LVEF between 40 and 49% are often 5. Cardiac imaging and other
classified as HFpEF in clinical trials.79 However, in the present guide- diagnostic tests
lines, we define HFpEF as an LVEF ≥50% and consider patients with
an LVEF between 40 and 49% as a grey area, which could be indi- Cardiac imaging plays a central role in the diagnosis of HF and in guiding
particularly in patients with regional LV dysfunction and/or LV re- 5.4 Stress echocardiography
modelling. Three-dimensional echocardiography of adequate quality Exercise or pharmacological stress echocardiography may be used
improves the quantification of LV volumes and LVEF and has the for the assessment of inducible ischaemia and/or myocardium viabil-
best accuracy compared with values obtained through CMR.95 ity99 and in some clinical scenarios of patients with valve disease (e.g.
Doppler techniques allow the calculation of haemodynamic vari- dynamic mitral regurgitation, low-flow – low-gradient aortic sten-
ables, such as stroke volume index and cardiac output, based on the osis).99,100 There are also suggestions that stress echocardiography
velocity time integral at the LV outflow tract area. may allow the detection of diastolic dysfunction related to exercise
In recent years, tissue Doppler parameters (S wave) and deform- exposure in patients with exertional dyspnoea, preserved LVEF and
ation imaging techniques (strain and strain rate) have been shown to inconclusive diastolic parameters at rest.85,86
be reproducible and feasible for clinical use, especially in detecting sub-
tle abnormalities in systolic function in the preclinical stage; however, 5.5 Cardiac magnetic resonance
Recommendations for cardiac imaging in patients with suspected or established heart failure
TTE is recommended for the assessment of myocardial structure and function in subjects with suspected HF in order to establish
I C
a diagnosis of either HFrEF, HFmrEF or HFpEF.
TTE is recommended to assess LVEF in order to identify patients with HF who would be suitable for evidence-based
I C
pharmacological and device (ICD, CRT) treatment recommended for HFrEF.
TTE is recommended for the assessment of valve disease, right ventricular function and pulmonary arterial pressure in patients with
I C
an already established diagnosis of either HFrEF, HFmrEF or HFpEF in order to identify those suitable for correction of valve disease.
TTE is recommended for the assessment of myocardial structure and function in subjects to be exposed to treatment which
I C
potentially can damage myocardium (e.g. chemotherapy).
Other techniques (including systolic tissue Doppler velocities and deformation indices, i.e. strain and strain rate), should be
IIa C
considered in a TTE protocol in subjects at risk of developing HF in order to identify myocardial dysfunction at the preclinical stage.
CMR is recommended for the assessment of myocardial structure and function (including right heart) in subjects with poor
I C
acoustic window and patients with complex congenital heart diseases (taking account of cautions/contra-indications to CMR).
CMR with LGE should be considered in patients with dilated cardiomyopathy in order to distinguish between ischaemic and non-
IIa C
ischaemic myocardial damage in case of equivocal clinical and other imaging data (taking account of cautions/contra-indications to CMR).
CMR is recommended for the characterization of myocardial tissue in case of suspected myocarditis, amyloidosis, sarcoidosis,
Chagas disease, Fabry disease non-compaction cardiomyopathy, and haemochromatosis (taking account of cautions/contra- I C
indications to CMR).
Non-invasive stress imaging (CMR, stress echocardiography, SPECT, PET) may be considered for the assessment of myocardial
ischaemia and viability in patients with HF and CAD (considered suitable for coronary revascularization) before the decision on IIb B 116–118
revascularization.
Invasive coronary angiography is recommended in patients with HF and angina pectoris recalcitrant to pharmacological
therapy or symptomatic ventricular arrhythmias or aborted cardiac arrest (who are considered suitable for potential coronary I C
revascularization) in order to establish the diagnosis of CAD and its severity.
Invasive coronary angiography should be considered in patients with HF and intermediate to high pre-test probability of CAD and
the presence of ischaemia in non-invasive stress tests (who are considered suitable for potential coronary revascularization) in IIa C
order to establish the diagnosis of CAD and its severity.
Cardiac CT may be considered in patients with HF and low to intermediate pre-test probability of CAD or those with equivocal
IIb C
non-invasive stress tests in order to rule out coronary artery stenosis.
AHF ¼ acute heart failure; CAD ¼ coronary artery disease; CMR ¼ cardiac magnetic resonance; CRT ¼ cardiac resynchronization therapy; CT ¼ computed tomography; HF ¼
heart failure; HFpEF ¼ heart failure with preserved ejection fraction; HFmrEF ¼ heart failure with mid-range ejection fraction; HFrEF ¼ heart failure with reduced ejection fraction;
ICD ¼ implantable cardioverter-defibrillator; LGE ¼ late gadolinium enhancement; LVEF ¼ left ventricular ejection fraction; PET ¼ positron emission tomography; SPECT ¼
single-photon emission computed tomography; TTE ¼ transthoracic echocardiography.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
ESC Guidelines 2145
5.10 Other diagnostic tests sessments and endomyocardial biopsy. The major typical indications
Comprehensive assessment of patients with HF comprises, besides are summarized in the recommendations table for diagnostic tests in
medical history and physical examination, including adequate imaging patients with HF. Although there is extensive research on biomarkers
techniques, a set of additional diagnostic tests, i.e. laboratory vari- in HF (e.g. ST2, galectin 3, copeptin, adrenomedullin), there is no def-
ables, ECG, chest X-ray, exercise testing, invasive haemodynamic as- inite evidence to recommend them for clinical practice.
- TSH
- ferritin, TSAT = TIBC
- natriuretic peptides IIa C
Additional diagnostic tests aiming to identify other HF aetiologies and comorbidities should be considered in individual
IIa C
patients with HF when there is a clinical suspicion of a particular pathology (see Table 3.4 on HF aetiologies).
A 12-lead ECG is recommended in all patients with HF in order to determine heart rhythm, heart rate, QRS morphology, and
I C
QRS duration, and to detect other relevant abnormalities. This information is needed to plan and monitor treatment.
Chest radiography (X-ray) is recommended in patients with HF to detect/exclude alternative pulmonary or other diseases,
which may contribute to dyspnoea. It may also identify pulmonary congestion/oedema and is more useful in patients with I C
suspected HF in the acute setting.
EMB should be considered in patients with rapidly progressive HF despite standard therapy when there is a probability of a
IIa C 93
IIb C 121
Ultrasound measurement of inferior vena cava diameter may be considered for the assessment of volaemia status in patients with HF. IIb C
AHF ¼ acute heart failure; ALT ¼ alanine aminotransferase; AST ¼ aspartate aminotransferase; BNP ¼ B-type natriuretic peptide; ECG ¼ electrocardiogram; eGFR ¼ estimated
glomerular filtration rate; EMB ¼ endomyocardial biopsy; GFR ¼ glomerular filtration rate; GGTP ¼ gamma-glutamyl transpeptidase; HbA1c ¼ glycated haemoglobin; HF ¼
heart failure; HFrEF ¼ heart failure with reduced ejection fraction; QRS ¼ Q, R, and S waves (combination of three of the graphical deflections); TIBC ¼ total iron-binding capacity;
TSAT ¼ transferrin saturation; TSH ¼ thyroid-stimulating hormone; WBC ¼ white blood cell.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
5.10.1 Genetic testing in heart failure sufficiently high and consistent to justify routine targeted genetic
Molecular genetic analysis in patients with cardiomyopathies is re- screening. Recommendations for genetic testing in patients with
commended when the prevalence of detectable mutations is HF are based on the position statement of the European Society
2146 ESC Guidelines
of Cardiology Working Group on Myocardial and Pericardial Dis- hypertensive patients reduces the risk of cardiovascular disease,
eases.94 In most patients with a definite clinical diagnosis of HF, there death and hospitalization for HF.129
is no confirmatory role for routine genetic testing to establish the Recently, empaglifozin (an inhibitor of sodium-glucose cotran-
diagnosis. Genetic counselling is recommended in patients with sporter 2), has been shown to improve outcomes (including the re-
HCM, idiopathic DCM and ARVC. Restrictive cardiomyopathy duction of mortality and HF hospitalizations) in patients with type 2
and isolated non-compaction cardiomyopathies are of a possible diabetes.130 Other hypoglycaemic agents have not been shown con-
genetic origin and should also be considered for genetic testing. vincingly to reduce the risk of cardiovascular events and may in-
HCM is mostly inherited as an autosomal dominant disease with crease the risk of HF. Intensification of hypoglycaemic therapy to
variable expressivity and age-related penetrance. Currently, more drive down glycated haemoglobin (HbA1c) with agents other than
than 20 genes and 1400 mutations have been identified, most of which empagliflozin does not reduce the risk of developing HF (for details
are located in the sarcomere genes encoding cardiac b-myosin heavy see Section 11.6 on diabetes).
In patients with asymptomatic LV systolic dysfunction (LVEF plantable cardioverter-defibrillator (ICD) is recommended to
,30%) of ischaemic origin who are ≥40 days after an AMI, an im- prolong life.149
Recommendations to prevent or delay the development of overt heart failure or prevent death before the onset of
symptoms
126, 129,
Treatment of hypertension is recommended to prevent or delay the onset of HF and prolong life. I A
150, 151
Treatment with statins is recommended in patients with or at high-risk of CAD whether or not they have LV systolic 137–140,
Counselling and treatment for smoking cessation and alcohol intake reduction is recommended for people who smoke or who
I C 131–134
consume excess alcohol in order to prevent or delay the onset of HF.
130, 141,
Treating other risk factors of HF (e.g. obesity, dysglycaemia) should be considered in order to prevent or delay the onset of HF. IIa C
153–155
IIa B 130
ACE-I is recommended in patients with asymptomatic LV systolic dysfunction and a history of myocardial infarction in order to 5, 144,
I A
prevent or delay the onset of HF and prolong life. 145
ACE-I is recommended in patients with asymptomatic LV systolic dysfunction without a history of myocardial infarction, in order
I B 5
to prevent or delay the onset of HF.
ACE-I should be considered in patients with stable CAD even if they do not have LV systolic dysfunction, in order to prevent
IIa A 142
or delay the onset of HF.
Beta-blocker is recommended in patients with asymptomatic LV systolic dysfunction and a history of myocardial infarction, in
I B 146
order to prevent or delay the onset of HF or prolong life.
ACEI ¼ angiotensin-converting enzyme inhibitor; CAD ¼ coronary artery disease; HF ¼ heart failure; ICD ¼ implantable cardioverter-defibrillator; LV ¼ left ventricular;
LVEF ¼ left ventricular ejection fraction; OMT ¼ optimal medical therapy
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
7. Pharmacological treatment of Figure 7.1 shows a treatment strategy for the use of drugs (and de-
vices) in patients with HFrEF. The recommendations for each treat-
heart failure with reduced ejection ment are summarized below.
fraction Neuro-hormonal antagonists (ACEIs, MRAs and beta-blockers)
have been shown to improve survival in patients with HFrEF and
7.1 Objectives in the management of are recommended for the treatment of every patient with HFrEF,
heart failure unless contraindicated or not tolerated. A new compound
(LCZ696) that combines the moieties of an ARB (valsartan) and a
The goals of treatment in patients with HF are to improve their clin-
neprilysin (NEP) inhibitor (sacubitril) has recently been shown to
ical status, functional capacity and quality of life, prevent hospital ad-
be superior to an ACEI (enalapril) in reducing the risk of death
mission and reduce mortality. The fact that several drugs for HF
and of hospitalization for HF in a single trial with strict inclusion/ex-
have shown detrimental effects on long-term outcomes, despite
clusion criteria.162 Sacubitril/valsartan is therefore recommended to
showing beneficial effects on shorter-term surrogate markers, has
replace ACEIs in ambulatory HFrEF patients who remain symptom-
led regulatory bodies and clinical practice guidelines to seek mortal-
atic despite optimal therapy and who fit these trial criteria. ARBs
ity/morbidity data for approving/recommending therapeutic inter-
have not been consistently proven to reduce mortality in patients
ventions for HF. However, it is now recognized that preventing
with HFrEF and their use should be restricted to patients intolerant
HF hospitalization and improving functional capacity are important
of an ACEI or those who take an ACEI but are unable to tolerate an
benefits to be considered if a mortality excess is ruled out.159 – 161
2148 ESC Guidelines
MRA. Ivabradine reduces the elevated heart rate often seen in Practical guidance on how to use ACE inhibitors is given in Web
HFrEF and has also been shown to improve outcomes, and should Table 7.4.
be considered when appropriate.
The above medications should be used in conjunction with diure- 7.2.2 Beta-blockers
tics in patients with symptoms and/or signs of congestion. The use of Beta-blockers reduce mortality and morbidity in symptomatic
diuretics should be modulated according to the patient’s clinical patients with HFrEF, despite treatment with an ACEI and, in
status. most cases, a diuretic,167,168,170,172,173 but have not been tested
The key evidence supporting the recommendations in this in congested or decompensated patients. There is consensus
section is given in Web Table 7.1. The recommended doses of these that beta-blockers and ACEIs are complementary, and can be
disease-modifying medications are given in Table 7.2. The started together as soon as the diagnosis of HFrEF is made.
recommendations given in Sections 7.5 and 7.6 summarize drugs There is no evidence favouring the initiation of treatment
ACEI ¼ angiotensin-converting enzyme inhibitor; HF ¼ heart failure; HFrEF ¼ 7.3 Other treatments recommended in
heart failure with reduced ejection fraction; MRA ¼ mineralocorticoid receptor
antagonist; NYHA ¼ New York Heart Association.
selected symptomatic patients with heart
a
Class of recommendation. failure with reduced ejection fraction
b
Level of evidence. 7.3.1 Diuretics
c
Reference(s) supporting recommendations.
d
Or ARB if ACEI is not tolerated/contraindicated Diuretics are recommended to reduce the signs and symptoms
of congestion in patients with HFrEF, but their effects on
ESC Guidelines 2149
Figure 7.1 Therapeutic algorithm for a patient with symptomatic heart failure with reduced ejection fraction. Green indicates a class I recom-
mendation; yellow indicates a class IIa recommendation. ACEI ¼ angiotensin-converting enzyme inhibitor; ARB ¼ angiotensin receptor blocker;
ARNI ¼ angiotensin receptor neprilysin inhibitor; BNP ¼ B-type natriuretic peptide; CRT ¼ cardiac resynchronization therapy; HF ¼ heart fail-
ure; HFrEF ¼ heart failure with reduced ejection fraction; H-ISDN ¼ hydralazine and isosorbide dinitrate; HR ¼ heart rate; ICD ¼ implantable
cardioverter defibrillator; LBBB ¼ left bundle branch block; LVAD ¼ left ventricular assist device; LVEF ¼ left ventricular ejection fraction; MR ¼
mineralocorticoid receptor; NT-proBNP ¼ N-terminal pro-B type natriuretic peptide; NYHA ¼ New York Heart Association; OMT ¼ optimal
medical therapy; VF ¼ ventricular fibrillation; VT ¼ ventricular tachycardia. aSymptomatic ¼ NYHA Class II-IV. bHFrEF ¼ LVEF ,40%. cIf ACE
inhibitor not tolerated/contra-indicated, use ARB. dIf MR antagonist not tolerated/contra-indicated, use ARB. eWith a hospital admission for
HF within the last 6 months or with elevated natriuretic peptides (BNP . 250 pg/ml or NTproBNP . 500 pg/ml in men and 750 pg/ml in women).
f
With an elevated plasma natriuretic peptide level (BNP ≥ 150 pg/mL or plasma NT-proBNP ≥ 600 pg/mL, or if HF hospitalization within recent
12 months plasma BNP ≥ 100 pg/mL or plasma NT-proBNP ≥ 400 pg/mL). gIn doses equivalent to enalapril 10 mg b.i.d. hWith a hospital admis-
sion for HF within the previous year. iCRT is recommended if QRS ≥ 130 msec and LBBB (in sinus rhythm). jCRT should/may be considered if
QRS ≥ 130 msec with non-LBBB (in a sinus rhythm) or for patients in AF provided a strategy to ensure bi-ventricular capture in place (individua-
lized decision). For further details, see Sections 7 and 8 and corresponding web pages.
2150 ESC Guidelines
mortality and morbidity have not been studied in RCTs. A Co- Loop diuretics produce a more intense and shorter diuresis
chrane meta-analysis has shown that in patients with chronic HF, than thiazides, although they act synergistically and the combin-
loop and thiazide diuretics appear to reduce the risk of death ation may be used to treat resistant oedema. However, adverse
and worsening HF compared with placebo, and compared effects are more likely and these combinations should only be
with an active control, diuretics appear to improve exercise used with care. The aim of diuretic therapy is to achieve and main-
capacity.178,179 tain euvolaemia with the lowest achievable dose. The dose of the
diuretic must be adjusted according to the individual needs over
time. In selected asymptomatic euvolaemic/hypovolaemic patients,
the use of a diuretic drug might be (temporarily) discontinued. Pa-
tients can be trained to self-adjust their diuretic dose based on
Table 7.2 Evidence-based doses of disease-modifying monitoring of symptoms/signs of congestion and daily weight
Other pharmacological treatments recommended in selected patients with symptomatic (NYHA Class II-IV) heart
failure with reduced ejection fraction
Digoxin
Digoxin may be considered in symptomatic patients in sinus rhythm despite treatment with an ACE-I (or ARB), a beta-blocker
IIb B 185
and an MRA, to reduce the risk of hospitalization (both all-cause and HF-hospitalizations).
N-3 PUFA
An n-3 PUFAe preparation may be considered in symptomatic HF patients to reduce the risk of cardiovascular hospitalization
IIb B 186
and cardiovascular death.
ACEI ¼ angiotensin-converting enzyme inhibitor; ARB ¼ angiotensin receptor blocker; BNP ¼ B-type natriuretic peptide; bpm ¼ beats per minute; HF ¼ heart failure; HFrEF ¼
heart failure with reduced ejection fraction; LVEF ¼ left ventricular ejection fraction; MRA ¼ mineralocorticoid receptor antagonist; NT-proBNP ¼ N-terminal pro-B type
natriuretic peptide; NYHA ¼ New York Heart Association; PUFA ¼ polyunsaturated fatty acid. OMT ¼ optimal medical therapy (for HFrEF this mostly comprises an ACEI or
sacubitril/valsartan, a beta-blocker and an MRA).
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
d
Patient should have elevated natriuretic peptides (plasma BNP ≥150 pg/mL or plasma NT-proBNP ≥600 pg/mL, or if HF hospitalization within the last 12 months, plasma BNP
≥100 pg/mL or plasma NT-proBNP ≥400 pg/mL) and able to tolerate enalapril 10 mg b.i.d.
e
Applies only to preparation studied in cited trial.
7.3.2 Angiotensin receptor neprilysin inhibitor physiologic effects through binding to NP receptors and the aug-
A new therapeutic class of agents acting on the RAAS and the neu- mented generation of cGMP, thereby enhancing diuresis, natriuresis
tral endopeptidase system has been developed [angiotensin recep- and myocardial relaxation and anti-remodelling. ANP and BNP also
tor neprilysin inhibitor (ARNI)]. The first in class is LCZ696, which is inhibit renin and aldosterone secretion. Selective AT1-receptor
a molecule that combines the moieties of valsartan and sacubitril blockade reduces vasoconstriction, sodium and water retention
(neprilysin inhibitor) in a single substance. By inhibiting neprilysin, and myocardial hypertrophy.187,188
the degradation of NPs, bradykinin and other peptides is slowed. A recent trial investigated the long-term effects of sacubi-
High circulating A-type natriuretic peptide (ANP) and BNP exert tril/valsartan compared with an ACEI (enalapril) on morbidity
2152 ESC Guidelines
and mortality in patients with ambulatory, symptomatic HFrEF Practical guidance on how to use ivabradine is given in Web
with LVEF ≤40% (this was changed to ≤35% during the Table 7.8.
study), elevated plasma NP levels (BNP ≥150 pg/mL or
NT-proBNP ≥600 pg/mL or, if they had been hospitalized 7.3.4 Angiotensin II type I receptor blockers
for HF within the previous 12 months, BNP ≥100 pg/mL or ARBs are recommended only as an alternative in patients intolerant
NT-proBNP ≥400 pg/mL), and an estimated GFR (eGFR) of an ACEI.182 Candesartan has been shown to reduce cardiovascu-
≥30 mL/min/1.73 m 2 of body surface area, who were able lar mortality.182 Valsartan showed an effect on hospitalization for HF
to tolerate separate treatments periods with enalapril (but not on all-cause hospitalizations) in patients with HFrEF receiv-
(10 mg b.i.d.) and sacubitril/valsartan (97/103 mg b.i.d.) during ing background ACEIs.194
a run-in period.162 In this population, sacubitril/valsartan (97/ The combination of ACEI/ARB for HFrEF was reviewed by the
103 mg b.i.d.) was superior to ACEI (enalapril 10 mg b.i.d.) in EMA, which suggested that benefits are thought to outweigh risks
hospitalization) in patients with AF receiving digoxin.195,196 How- underlying CAD or/and hyperlipidaemia, a continuation of this
ever, this remains controversial, as another recent meta-analysis therapy should be considered.
concluded on the basis of non-RCTs that digoxin has no deleterious
effect on mortality in patients with AF and concomitant HF, most of
whom had HFrEF.197 7.5.2 Oral anticoagulants and antiplatelet therapy
In patients with symptomatic HF and AF, digoxin may be use- Other than in patients with AF (both HFrEF and HFpEF), there is no
ful to slow a rapid ventricular rate, but it is only recommended evidence that an oral anticoagulant reduces mortality/morbidity
for the treatment of patients with HFrEF and AF with rapid ven- compared with placebo or aspirin.206,207 Studies testing the non-
tricular rate when other therapeutic options cannot be pur- vitamin K antagonist oral anticoagulants (NOACs) in patients with
sued. 196,198 – 201 Of note, the optimal ventricular rate for HFrEF are currently ongoing. Patients with HFrEF receiving oral an-
patients with HF and AF has not been well established, but ticoagulation because of concurrent AF or risk of venous thrombo-
7.6 Treatments not recommended specific guideline recommendations for other therapeutic technolo-
(believed to cause harm) in symptomatic gies, including baroreflex activation therapy,217 vagal stimulation,218
diaphragmatic pacing219,220 and cardiac contractility modula-
patients with heart failure with reduced tion;221,222 further research is required. Implantable devices to
ejection fraction monitor arrhythmias or haemodynamics are discussed elsewhere
7.6.1 Calcium-channel blockers in these guidelines.
Non-dihydropyridine calcium-channel blockers (CCBs) are not in-
dicated for the treatment of patients with HFrEF. Diltiazem and ver-
apamil have been shown to be unsafe in patients with HFrEF.214 8.1 Implantable cardioverter-defibrillator
There is a variety of dihydropyridine CCBs; some are known to A high proportion of deaths among patients with HF, especially
increase sympathetic tone and they may have a negative safety pro- those with milder symptoms, occur suddenly and unexpectedly.
CAD ¼ coronary artery disease; CRT ¼ cardiac resynchronization therapy; DCM ¼ dilated cardiomyopathy; HF ¼ heart failure; ICD ¼ implantable cardioverter-defibrillator;
IHD ¼ ischaemic heart disease; LVEF ¼ left ventricular ejection fraction; MI ¼ myocardial infarction; NYHA ¼ New York Heart Association, OMT ¼ optimal medical therapy.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
8.1.1 Secondary prevention of sudden cardiac death survival; the decision to implant should take into account the
Compared with amiodarone treatment, ICDs reduce mortality patient’s view and their quality of life, the LVEF (survival bene-
in survivors of cardiac arrest and in patients who have experi- fit is uncertain when the LVEF is .35%) and the absence of
enced sustained symptomatic ventricular arrhythmias. An ICD other diseases likely to cause death within the following
is recommended in such patients when the intent is to increase year.223 – 225
ESC Guidelines 2155
8.1.2 Primary prevention of sudden cardiac death ICD therapy is not recommended in patients in NYHA Class IV
Although amiodarone may have reduced mortality in older trials of with severe symptoms refractory to pharmacological therapy who
HF,242,243 contemporary studies conducted since the widespread are not candidates for CRT, a ventricular assist device or cardiac
introduction of beta-blockers suggest that it does not reduce mor- transplantation, because such patients have a very limited life ex-
tality in patients with HFrEF.227,244,245 Dronedarone246,247 and class pectancy and are likely to die from pump failure.
I antiarrhythmic agents246,248 should not be used for prevention of Patients with serious co-morbidities who are unlikely to survive
arrhythmias in this population. substantially more than 1 year are unlikely to obtain substantial
Some guideline-recommended therapies, including beta- benefit from an ICD.229 – 233
blockers, MRAs, sacubitril/valsartan and pacemakers with CRT Patients should be counselled as to the purpose of an ICD, com-
(CRT-Ps), reduce the risk of sudden death (see Section 7). plications related to implantation and device activation (predomin-
An ICD reduces the rate of sudden arrhythmic death in patients antly inappropriate shocks) and under what circumstances it might
Recommendations for cardiac resynchronization therapy implantation in patients with heart failure
AF ¼ atrial fibrillation; AV ¼ atrio-ventricular; CRT ¼ cardiac resynchronization therapy; HF ¼ heart failure; HFrEF ¼ heart failure with reduced ejection fraction; ICD ¼
implantable cardioverter-defibrillator; LBBB ¼ left bundle branch block; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association; OMT ¼ optimal medical
therapy; QRS ¼ Q, R and S waves (combination of three of the graphical deflections); RV ¼ right ventricular.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
d
Use judgement for patients with end-stage HF who might be managed conservatively rather than with treatments to improve symptoms or prognosis.
CRT improves cardiac performance in appropriately selected pa- CRT response and was the inclusion criterion in all randomized
tients and improves symptoms286 and well-being286 and reduces trials. But QRS morphology has also been related to a beneficial re-
morbidity and mortality.266 Of the improvement in quality-adjusted sponse to CRT. Several studies have shown that patients with left
life-years (QALYs) with CRT among patients with moderate to se- bundle branch block (LBBB) morphology are more likely to respond
vere HF, two-thirds may be attributed to improved quality of life and favourably to CRT, whereas there is less certainty about patients
one-third to increased longevity.287 with non-LBBB morphology. However, patients with LBBB morph-
Only the COMPANION265 and CARE-HF trials262,263 compared ology often have wider QRS duration, and there is a current debate
the effect of CRT to guideline-advised medical therapy. Most other about whether QRS duration or QRS morphology is the main pre-
trials have compared CRT-D to ICD, and a few have compared dictor of a beneficial response to CRT. Evidence from two IPD
CRT-P to backup pacing. The prevention of lethal bradycardia might meta-analyses indicates that after accounting for QRS duration,
be an important mechanism of benefit shared by all pacing devices. there is little evidence to suggest that QRS morphology or aetiology
In CARE-HF, at baseline, 25% of patients had a resting heart rate of of disease influence the effect of CRT on morbidity or mortal-
≤60 bpm.262 – 264 If prevention of bradycardia is important, the ef- ity.266,273 In addition, none of the landmark trials selected patients
fect of CRT will appear greater in trials where there is no device for inclusion according to QRS morphology, sex or ischaemic aeti-
in the control group. ology, nor were they powered for subgroup analyses.
Most studies of CRT have specified that the LVEF should be ,35%, The Echo-CRT283,284 trial and an IPD meta-analysis266 suggest
but RAFT267 and MADIT-CRT268,269 specified an LVEF ,30%, while possible harm from CRT when QRS duration is ,130 ms, thus im-
REVERSE270 – 272 specified ,40% and BLOCK-HF274 ,50%. Rela- plantation of CRT is not recommended if QRS duration is ,130
tively few patients with an LVEF of 35–40% have been randomized, ms.266,283,284
but an individual participant data (IPD) meta-analysis suggests no If a patient is scheduled to receive an ICD and is in sinus rhythm
diminution of the effect of CRT in this group.266 with a QRS duration ≥130 ms, CRT-D should be considered if
Not all patients respond favourably to CRT.286 Several character- QRS is between 130 and 149 ms and is recommended if QRS is
istics predict improvement in morbidity and mortality, and the ex- ≥150 ms. However, if the primary reason for implanting a CRT
tent of reverse remodelling is one of the most important is for the relief of symptoms, then the clinician should choose
mechanisms of action of CRT. Patients with ischaemic aetiology CRT-P or CRT-D, whichever they consider appropriate. Clinical
will have less improvement in LV function due to myocardial scar tis- practice varies widely among countries. The only randomized trial
sue, which is less likely to undergo favourable remodelling.288 Con- to compare CRT-P and CRT-D265 failed to demonstrate a differ-
versely, women may be more likely to respond than men, possibly ence in morbidity or mortality between these technologies.288 If
due to smaller body and heart size.273,285,289 QRS width predicts the primary reason for implanting CRT is to improve prognosis,
ESC Guidelines 2157
then the majority of evidence lies with CRT-D for patients in enhance contractile performance without activating extra systolic
NYHA Class II and with CRT-P for patients in NYHA Classes contractions. CCM has been evaluated in patients with HFrEF in
III – IV. It is unclear whether CRT reduces the need for an ICD NYHA Classes II – III with normal QRS duration (,120 ms).221,222
(by reducing the arrhythmia burden) or increases the benefit An individual patient data meta-analysis demonstrated an improve-
from an ICD (by reducing mortality rates from worsening HF, lead- ment in exercise tolerance (peak VO2) and quality of life (Minnesota
ing to longer exposure to the risk of arrhythmia). Living with Heart Failure questionnaire). Thus CCM may be consid-
When LVEF is reduced, RV pacing may exacerbate cardiac dyssyn- ered in selected patients with HF. The effect of CCM on HF morbid-
chrony. This can be prevented by CRT, which might improve patient ity and mortality remains to be established.
outcomes.274,275,277,290 However, a difference in outcome was not Most other devices under evaluation involve some modification
observed between CRT and RV pacing in a subgroup analysis of of the activity of the autonomic nervous system (ANS) by targeted
RAFT267 or in patients without HFrEF in BioPACE.291 On balance, electrical stimulation.298,299 These include vagal nerve stimulation,
9.1 Effect of treatment on symptoms and in cardiovascular mortality.130 However, aggressive manage-
in heart failure with preserved ejection ment of dysglycaemia may be harmful.153,320
Myocardial ischaemia may contribute to symptoms, morbidity
fraction and mortality and should be considered when assessing patients.
Diuretics will usually improve congestion, if present, thereby im- However, there is only anecdotal evidence that revascularization
proving symptoms and signs of HF. The evidence that diuretics improves symptoms or outcome. Patients with angina should follow
improve symptoms is similar across the spectrum of LVEF.178,179 the same management route as patients with HFrEF.112
Evidence that beta-blockers and MRAs improve symptoms in Patients with HFpEF and HFmrEF have impaired exercise toler-
these patients is lacking. There is inconsistent evidence for an im- ance, commonly accompanied by an augmented blood pressure re-
provement in symptoms in those treated with ARBs (only for can- sponse to exercise and chronotropic incompetence. Combined
desartan was there an improvement in NYHA class)309,310 and endurance/resistance training appears safe for patients with HFpEF
ACEIs.311
10.1 Atrial fibrillation must not be given. Longer-term infusion of amiodarone should be
AF is the most common arrhythmia in HF irrespective of concomi- given only by central or long-line venous access to avoid peripheral
tant LVEF; it increases the risk of thromboembolic complications vein phlebitis. In patients with haemodynamic collapse, emergency
(particularly stroke) and may impair cardiac function, leading to electrical cardioversion is recommended (see also Section 12).
worsening symptoms of HF.316 Incident HF precipitated by AF is as-
sociated with a more benign prognosis,331 but new-onset AF in a pa- Recommendations for initial management of a
tient with established HF is associated with a worse outcome, rapid ventricular rate in patients with heart failure and
probably because it is both a marker of a sicker patient and because atrial fibrillation in the acute or chronic setting
it impairs cardiac function.332,333 Patients with chronic HF and per-
manent AF have a worse outcome than those in sinus rhythm, al- Recommendations Class a Level b Ref c
though this is largely explained by more advanced age and HF Urgent electrical cardioversion is
ventricular rate to be assessed during rest, exercise and sleep, but cardioversion.343 – 346 When used, the need for continued administra-
the value of routine monitoring has not yet been established. Im- tion of amiodarone should be regularly reviewed and justified.
planted devices such as pacemakers, CRT or ICDs can also be The safety and efficacy of catheter ablation in the atria and pul-
used to measure ventricular rate. monary veins (PV) as a rhythm control strategy in HF is at present
The optimal resting ventricular rate in patients with AF and HF is uncertain except for tachycardia induced cardiomyopathy.316 One
uncertain but may be between 60 – 100 bpm.350,352 – 354 One trial small study suggested that AF ablation was superior to AV node ab-
suggested that a resting ventricular rate of up to 110 bpm might still lation and CRT.360 Another study, including 203 patients with per-
be acceptable,198,202 and 2016 ESC AF guidelines recommend this sistent AF, HF and an ICD or CRT device, showed that AF ablation
threshold as the target for rate control therapy.316 However, this was superior to amiodarone in correcting AF, and this was asso-
Task Force believes that a lower rate for patients with HF may be ciated with fewer hospitalizations for HF and lower mortality.
preferable (60 – 100 bpm). Ventricular rates ,70 bpm are asso- Two small studies of AF ablation compared with rate control met
10.1.5 Thromboembolism prophylaxis HF and AF who have mechanical heart valves or at least moderate mi-
Patients with HF and AF should generally be anticoagulated and the tral stenosis, only oral vitamin K antagonists should be used for pre-
balance of benefit and risk of bleeding (using CHA2DS2-VASc and vention of thromboembolic stroke.370
HAS-BLED scores; for details, please see Web Tables 10.1 and The dabigatran dose should be reduced to 110 mg b.i.d. when cre-
10.2.) should be evaluated as recommended in the ESC guidelines atinine clearance is 30 –49 mL/min, rivaroxaban to 15 mg daily and
for AF.316 A substantial proportion of patients with HF will have edoxaban to 30 mg daily when creatinine clearance is 30 – 50 mL/
both benefit and risk scores ≥3, indicating that careful consider- min and apixaban to 2.5 mg twice daily if a patient has two or
ation should be given before prescribing an oral anticoagulant and more of the following: age ≥80 years, serum creatinine ≥1.5 mg/
that regular review is subsequently needed (and correctable risk dL or body weight ≤60 kg.370 – 375 The summary of the recommen-
factors for bleeding addressed) if an oral anticoagulant is given. dations for the prevention of thromboembolism in patients with
NOACs are preferred for patients with HF with non-valvular AF, as symptomatic HF and paroxysmal or persistent/permanent AF is
Recommendations for the prevention of thrombo-embolism in patients with symptomatic heart failure (NYHA Class II –
IV) and paroxysmal or persistent/permanent atrial fibrillation
AF ¼ atrial fibrillation; CHA2DS2-VASc ¼ Congestive heart failure or left ventricular dysfunction, Hypertension, Age ≥ 75 (doubled), Diabetes, Stroke (doubled)-Vascular disease,
Age 65 –74, Sex category (female); HAS-BLED ¼ Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio,
Elderly (.65 years), Drugs/alcohol concomitantly (1 point each); HF ¼ heart failure; LMWH ¼ low molecular weight heparin; NOAC ¼ non-vitamin K antagonist oral
anticoagulant; NYHA ¼ New York Heart Association; TOE ¼ transoesophageal echocardiography.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
10.2 Ventricular arrhythmias revascularization for patients with HFrEF have not reduced overall
The initial management of asymptomatic ventricular arrhythmias mortality,107,385 even in subgroups of patients with angina or myo-
is correction of electrolyte abnormalities, particularly low serum cardial ischaemia,115,386 but further analysis did suggest a reduction
potassium and magnesium, withdrawal of agents that might in sudden deaths.387
provoke arrhythmias and, in patients with HFrEF, optimization Amiodarone (often in combination with a beta-blocker) may be
of pharmacological therapy with ACEIs, beta-blockers and used to suppress symptomatic ventricular arrhythmias, but it may
MRAs and sacubitril/valsartan, which all reduce the risk of sudden adversely affect prognosis, especially in patients with more severe
death.174,177,383,384 HF.227,244 Other antiarrhythmic drugs should be avoided.247 Trans-
The clinical relevance of myocardial ischaemia for the provoca- catheter radiofrequency modification of the arrhythmogenic sub-
tion of ventricular arrhythmias is uncertain, although anecdotal strate may reduce the number of appropriate ICD discharges
cases of ischaemia-induced arrhythmias exist. Randomized trials of and may be used to terminate arrhythmic storm in patients with
2162 ESC Guidelines
HF and frequent, recurrent ventricular tachyarrhythmias and amiodarone, digoxin and ivabradine. For patients in AF, a reduction
therefore should be considered in such patients. Seeking the in the dose of beta-blockers allowing the daytime resting ventricular
advice of the members of the HF Team with expertise in electro- rate to rise to 70– 90 bpm may be considered, since evidence that
physiology is recommended in patients with recalcitrant ventricu- beta-blockers improve outcome in patients with AF is lacking.177 For
lar arrhythmias. For further details we refer the reader to the ESC/ patients with pauses but in sinus rhythm, a reduction in the dose of
EHRA guidelines on ventricular arrhythmias and sudden cardiac beta-blockers should be avoided unless the pauses are symptomatic,
death.260 prolonged or frequent, in which case the relative merits of dose re-
duction, beta-blocker withdrawal and (biventricular) pacing may be
considered. However, evidence is lacking to support a strategy of
Recommendations for the management of ventricular
pacing solely to permit initiation or titration of beta-blocker therapy
tachyarrhythmias in heart failure
in the absence of a conventional pacing indication; this strategy is not
Recommendations for the treatment of stable angina pectoris with symptomatic (NYHA Class II-IV) heart failure with
reduced ejection fraction112,113
I A 167–173
bpm ¼ beats per minute; HF ¼ heart failure; HFrEF ¼ heart failure with reduced ejection fraction; NYHA ¼ New York Heart Association.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
11.3 Cachexia and sarcopenia (for frailty, resistance, reduced anabolic drive, prolonged immobilization and
please refer to Section 14) physical deconditioning, together characterized by catabolic/anabol-
ic imbalance.418 Skeletal muscle wasting, when associated with im-
Cachexia is a generalized wasting process affecting all body com-
paired mobility and symptoms (termed sarcopenia or myopenia),
partments [i.e. lean tissue (skeletal muscle), fat tissue (energy re-
occurs in 30 – 50% of patients with HFrEF.419 In its most severe
serves) and bone tissue (osteoporosis)]. It may occur in 5–15% of
form it is associated with frailty and poor morbidity and mortality.420
patients with HF, especially those with HFrEF, and more advanced
Potential treatments may include appetite stimulants, exercise
disease status.414 – 416 This serious complication is associated with
training120 and anabolic agents, including testosterone, in combin-
more severe symptoms and reduced functional capacity, more fre-
ation with the application of nutritional supplements and
quent hospitalization and decreased survival. Cachexia in HF can be
anti-catabolic interventions, although none is of proven benefit
diagnosed and defined as involuntary non-oedematous weight loss
and their safety is unknown.421
≥6% of total body weight within the previous 6–12 months.414 – 417
The causes are multifactorial, and in individual patients they are
difficult to determine. These may include pro-inflammatory immune 11.4 Cancer
activation, neurohormonal derangements, poor nutrition and mal- Certain chemotherapeutic agents can cause (or aggravate) LV sys-
absorption, impaired calorie and protein balance, anabolic hormone tolic dysfunction and HF. The best recognized of these are the
ESC Guidelines 2165
anthracyclines (e.g. doxorubicin), trastuzumab and tyrosine kinase in depressive symptoms or improvement in cardiovascular status
inhibitors.397,422 A recent Cochrane review found that dexrazoxane compared with placebo in HFrEF patients, but this trial was not
may confer some cardioprotection in patients receiving anthracy- powered enough to prove the latter. 435 Similarly, escitalopram
clines.423 Pre- and post-evaluation of LVEF, if available with myocar- had no effect on either depression or clinical outcomes during the
dial strain imaging, is essential in patients receiving cardiotoxic 24-month follow-up as compared with placebo in patients with
chemotherapy, as detailed elsewhere.397,422 A risk score for identi- HFrEF and depression. Importantly, tricyclic antidepressants should
fying women with breast cancer at risk of developing HF during tras- be avoided, because they may cause hypotension, worsening HF and
tuzumab therapy has been developed based on age, chemotherapy arrhythmias.429,435
details, baseline cardiovascular status and other co-morbidities, and
may be helpful. 424 Chemotherapy should be discontinued and 11.6 Diabetes
HFrEF therapy commenced in patients developing moderate to se- Dysglycaemia and diabetes are very common in HF, and diabetes is
As glycaemic derangement progresses, the judgement on gly- The management of acute hyperkalaemia (.6.0 mmol/L) may re-
caemic control should be made according to cardiac conditions, quire a short-term cessation of potassium-retaining agents and
and if the new anti-diabetic drugs are to be prescribed, they have RAAS inhibitors, but this should be minimized and RAAS inhibitors
to be closely monitored by an HF team. should be carefully reintroduced as soon as possible while monitor-
ing potassium levels. A Cochrane review452 found no trial evidence
of major outcome benefits for any emergency therapy regimen for
11.7 Erectile dysfunction
hyperkalaemia. Two new potassium binders (patiromer and sodium
Erectile dysfunction is a common and important component of qual-
zirconium cyclosilicate) are currently under consideration for regu-
ity of life in men with HF.444,445 Its treatment should include optimal
latory approval.453,454 Initial results from patients with HF are avail-
therapies for underlying cardiovascular diseases and other interfer-
able and confirm the efficacy of these therapies in reducing serum
ing co-morbidities (e.g. diabetes) and amelioration of anxiety and
potassium455 and preventing recurrent hyperkalaemia in patients
Recommendations for the treatment of hypertension in patients with symptomatic (NYHA Class II-IV) heart failure with
reduced ejection fraction
ACE ¼ angiotensin-converting enzyme; ARB ¼ angiotensin receptor blocker; HF ¼ heart failure; HFmrEF ¼ heart failure with mid-range ejection fraction; HFpEF ¼ heart failure
with preserved ejection fraction; HFrEF ¼ heart failure with reduced ejection fraction; MRA ¼ mineralocorticoid receptor antagonist; NYHA ¼ New York Heart Association.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
11.12 Iron deficiency and anaemia i.v. iron therapy in HFrEF patients with iron deficiency over up
Iron deficiency is common in HF, as it is with other chronic ill- to 52 weeks showed reduced hospitalization rates and improved
nesses, and it can lead to anaemia and/or skeletal muscle dysfunc- HF symptoms, exercise capacity and quality of life.472 Treatment
tion without anaemia.466 Within an HF population, iron deficiency with FCM may therefore result in sustainable improvement in func-
is associated with a worse prognosis.467,468 Intravenous iron has tional capacity, symptoms and quality of life. Treatment was also
been specifically studied in two RCTs in patients with HF and associated with a significant reduction in hospitalizations for wor-
iron deficiency (serum ferritin ,100 mg/L or ferritin between sening HF. The number of deaths and the incidence of adverse
100 and 299 mg/L and transferrin saturation ,20%)469,470 both events were similar. Neither i.v. iron trial was powered to test
with and without anaemia. Intravenous ferric carboxymaltose for an effect on major outcomes or to evaluate separately the ef-
(FCM) has been shown to improve self-reported patient global as- fects in anaemic and non-anaemic patients. The effect of treating
sessment, quality of life and NYHA class (over 6 months) in the iron deficiency in HFpEF/HFmrEF and the long-term safety of
FAIR-HF trial469 both in anaemic and non-anaemic patients with iron therapy in either HFrEF, HFmrEF or HFpEF is unknown. The
HF, 471 and in the CONFIRM-HF trial 470 , exercise capacity im- safety of i.v. iron is unknown in patients with HF and haemoglobin
proved over 24 weeks. In the analysis of secondary endpoints in .15 g/dL.469,470 Patients with iron deficiency need to be screened
the CONFIRM-HF trial, i.v. iron reduced the risk of HF hospitaliza- for any potentially treatable/reversible causes (e.g. gastrointestinal
tions in iron-deficient patients with HFrEF.470 A meta-analysis of sources of bleeding).
2168 ESC Guidelines
Recommendations for the treatment of other functional status, greater risk of HF hospitalization and reduced sur-
co-morbidities in patients with heart failure vival. A diagnostic workup to seek a cause for any finding of anaemia
is indicated (e.g. occult blood loss, iron deficiency, B12/folate defi-
Recommendations Class a Level b Ref c ciency, blood dyscrasias), although in many patients no specific
cause is found. The erythropoietin-stimulating agent darbepoetin
alfa did not improve clinical outcomes in HFrEF patients with mild
Intravenous FCM should be to moderate anaemia, but led to an excess of thromboembolic
considered in symptomatic patients
events and is therefore not recommended.475
(serum ferritin <100 µg/L, or
ferritin between 100–299 µg/L and IIa A 469, 470
transferrin saturation <20%) in
order to alleviate HF symptoms, 11.13 Kidney dysfunction (including
kidney injury (CI-AKI)]. Renal dysfunction and worsening renal function established that obesity is associated with lower mortality across a
is further discussed in the section about AHF (see Section 12). wide range of body mass indexes (BMIs) (see also cachexia in Section
Prostatic obstruction is common in older men and can interfere 11.3)—the so-called obesity paradox also seen in other chronic ill-
with renal function; it should therefore be ruled out in men with HF nesses.414,416 Obesity should be managed as recommended in the
with deteriorating renal function. a-adrenoceptor blockers cause ESC guidelines on cardiovascular disease prevention,483 if the aim is
hypotension and sodium and water retention, and may not be to prevent future development of HF. However, these guidelines do
safe in HFrEF.458,464,465 For these reasons, 5-a-reductase inhibitors not refer to the HF patient in whom higher BMI is not adverse, and, al-
are generally preferred in the medical treatment of prostatic though often recommended for symptom benefit and risk factor con-
obstruction in patients with HF. trol, weight loss as an intervention has never been prospectively shown
to be either beneficial or safe in HFrEF. When weight loss is occurring
11.14 Lung disease (including asthma and in HF, it is associated with high mortality and morbidity, worse symp-
The safety and efficacy of alternative approaches to treating CSA Primary (organic) mitral regurgitation
in HFrEF patients, such as implantable phrenic nerve stimula- Surgery is indicated in symptomatic patients with severe organic
tion,219,220,492 are presently undergoing clinical investigation and mitral regurgitation with no contra-indications to surgery. The deci-
may require additional long term study. sion of whether to replace or repair depends mostly on valve anat-
omy, surgical expertise available, and the patient’s condition.
11.17. Valvular heart disease When the LVEF is , 30%, a durable surgical repair may improve
Valvular heart disease may cause or aggravate HF. This section brief- symptoms, although its effect on survival is unknown. In this situ-
ly addresses problems particularly relevant to HF, and the reader is ation, the decision to operate should take account of response to
referred to the recent guidelines on valvular disease for more medical therapy, co-morbidities, and the likelihood that the valve
information.493,494 can be repaired (rather than replaced).
Patients with HF and concomitant valvular heart disease constitute a
Secondary mitral regurgitation
In patients with severe aortic regurgitation, aortic valve repair or replacement is recommended in all symptomatic patients and
Evidence-based medical therapy in patients with HFrEF is recommended in order to reduce functional mitral regurgitation. I C
Combined surgery of secondary mitral regurgitation and coronary artery bypass grafting should be considered in symptomatic
IIa C
patients with LV systolic dysfunction (LVEF <30%), requiring coronary revascularization for angina recalcitrant to medical therapy.
Isolated surgery of non-ischaemic regurgitant mitral valve in patients with severe functional mitral regurgitation and severe LV systolic
IIb C
dysfunction (LVEF <30%) may be considered in selected patients in order to avoid or postpone transplantation.
HFrEF ¼ heart failure with reduced ejection fraction; LV ¼ left ventricular; LVEF ¼ left ventricular ejection fraction; TAVI ¼ transaortic valve implantation.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
AHF refers to rapid onset or worsening of symptoms and/or signs Infection (e.g. pneumonia, infective endocarditis, sepsis).
of HF. It is a life-threatening medical condition requiring urgent
evaluation and treatment, typically leading to urgent hospital Bradyarrhythmia.
admission. Toxic substances (alcohol, recreational drugs).
AHF may present as a first occurrence (de novo) or, more fre-
Drugs (e.g. NSAIDs, corticosteroids, negative inotropic substances,
quently, as a consequence of acute decompensation of chronic cardiotoxic chemotherapeutics).
HF, and may be caused by primary cardiac dysfunction or precipi-
Exacerbation of chronic obstructive pulmonary disease.
tated by extrinsic factors, often in patients with chronic HF. Acute
Pulmonary embolism.
myocardial dysfunction (ischaemic, inflammatory or toxic), acute
valve insufficiency or pericardial tamponade are among the most Surgery and perioperative complications.
frequent acute primary cardiac causes of AHF. Decompensation Increased sympathetic drive, stress-related cardiomyopathy.
of chronic HF can occur without known precipitant factors, but Metabolic/hormonal derangements (e.g. thyroid dysfunction, diabetic
more often with one or more factors, such as infection, uncon- ketosis, adrenal dysfunction, pregnancy and peripartum related
trolled hypertension, rhythm disturbances or non-adherence with abnormalities).
drugs/diet (Table 12.1). Cerebrovascular insult.
A large number of overlapping classifications of AHF based on dif- Acute mechanical cause: myocardial rupture complicating ACS (free wall
ferent criteria have been proposed.510 – 513 In practice the most use- rupture, ventricular septal defect, acute mitral regurgitation), chest trauma
ful classifications are those based on clinical presentation at or cardiac intervention, acute native or prosthetic valve incompetence
secondary to endocarditis, aortic dissection or thrombosis.
admission, allowing clinicians to identify patients at high risk of com-
plications and to direct management at specific targets, which cre-
ACS ¼ acute coronary syndromes; NSAIDs ¼ non-steroidal anti-inflammatory
ates a pathway for personalized care in the AHF setting. In most drugs.
cases, patients with AHF present with either preserved (90 – 140
mmHg) or elevated (.140 mmHg; hypertensive AHF) systolic
blood pressure (SBP). Only 5 – 8% of all patients present with Another approach is to classify patients according to the presence
low SBP (i.e. ,90 mmHg; hypotensive AHF), which is associated of the following precipitants/causes leading to decompensation,
with poor prognosis, particularly when hypoperfusion is also which need to be treated/corrected urgently (see Section 12.3.1):
present.514,515 ACS, hypertensive emergency, rapid arrhythmias or severe
2172 ESC Guidelines
bradycardia/conduction disturbance, acute mechanical cause under- rales and S3 gallop; class III, with frank acute pulmonary oedema;
lying AHF or acute pulmonary embolism. class IV, cardiogenic shock, hypotension (SBP ,90 mmHg) and evi-
Clinical classification can be based on bedside physical examination dence of peripheral vasoconstriction such as oliguria, cyanosis and
in order to detect the presence of clinical symptoms/signs of conges- diaphoresis.
tion (‘wet’ vs. ‘dry’ if present vs. absent) and/or peripheral hypoperfu- Definitions of the terms used in this section related to clinical
sion (‘cold’ vs. ‘warm’ if present vs. absent) (Figure 12.1).514,515 The presentation of patients with AHF are provided in Table 12.2.
combination of these options identifies four groups: warm and wet
(well perfused and congested) —most commonly present; cold and 12.2 Diagnosis and initial prognostic
wet (hypoperfused and congested); cold and dry (hypoperfused with- evaluation
out congestion); and warm and dry (compensated, well perfused with- The diagnostic workup needs to be started in the pre-hospital set-
out congestion). This classification may be helpful to guide therapy in ting and continued in the emergency department (ED) in order to
the initial phase and carries prognostic information.510,514,515 establish the diagnosis in a timely manner and initiate appropriate
Patients with HF complicating AMI can be classified according to management. The greater benefit of early treatment is well estab-
Killip and Kimball13 into class I, no clinical signs of HF; class II, HF with lished in ACS and now needs to be considered in the setting of
ESC Guidelines 2173
Table 12.2 Definitions of the terms used in Section 12 on acute heart failure
Term
Symptoms/signs of congestion (left-sided) Orthopnoea, paroxysmal nocturnal dyspnoea, pulmonary rales (bilateral), peripheral oedema (bilateral).
Symptoms/signs of congestion (right-sided)
symptoms of gut congestion.
Symptoms/signs of hypoperfusion Clinical: cold sweated extremities, oliguria, mental confusion, dizziness, narrow pulse pressure.
Laboratory measures: metabolic acidosis, elevated serum lactate, elevated serum creatinine.
Hypoperfusion is not synonymous with hypotension, but often hypoperfusion is accompanied by hypotension.
Hypotension Systolic BP <90 mmHg
Bradycardia Heart rate <40 bpm
BP ¼ blood pressure; bpm ¼ beats per minute; PaCO2 ¼ partial pressure of carbon dioxide in arterial blood; PaO2 ¼ partial pressure of oxygen in arterial blood; SaO2 ¼ oxygen
saturation.
AHF.516,517 In parallel, coexisting life-threatening clinical conditions † Chest X-ray can be a useful test for the diagnosis of AHF. Pulmon-
and/or precipitants that require urgent treatment/correction need ary venous congestion, pleural effusion, interstitial or alveolar oe-
to be immediately identified and managed (Figure 12.2). Typically, dema and cardiomegaly are the most specific findings for AHF,
an initial step in the diagnostic workup of AHF is to rule out alter- although in up to 20% of patients with AHF, chest X-ray is nearly
native causes for the patient’s symptoms and signs (i.e. pulmonary normal.519 Supine chest radiographs are of limited value in AHF.
infection, severe anaemia, acute renal failure). Chest X-ray is also useful to identify alternative non-cardiac dis-
When AHF is confirmed clinical evaluation is mandatory to select eases that may cause or contribute to the patient’s symptoms
further management. (i.e. pneumonia, non-consolidative pulmonary infections).
It is recommended that initial diagnosis of AHF should be based † ECG is rarely normal in AHF (high negative predictive value).520 It
on a thorough history assessing symptoms, prior cardiovascular his- is also helpful in identifying underlying cardiac disease and poten-
tory and potential cardiac and non-cardiac precipitants, as well as on tial precipitants (rapid AF, acute myocardial ischaemia).
the assessment of signs/symptoms of congestion and/or hypoperfu- † Immediate echocardiography is mandatory only in patients with
sion by physical examination and further confirmed by appropriate haemodynamic instability (particularly in cardiogenic shock)
additional investigations such as ECG, chest X-ray, laboratory as- and in patients suspected of acute life-threatening structural or
sessment (with specific biomarkers) and echocardiography. functional cardiac abnormalities (mechanical complications,
In patients presenting with AHF, early initiation of appropriate acute valvular regurgitation, aortic dissection). Early echocardiog-
therapy (along with relevant investigations) is of key import- raphy should be considered in all patients with de novo AHF and in
ance.516 – 518 those with unknown cardiac function; however, the optimal tim-
Typically, symptoms and signs of AHF reflect fluid overload (pul- ing is unknown (preferably within 48 h from admission, if the ex-
monary congestion and/or peripheral oedema) or, less often, re- pertise is available). Pocket-size echocardiography may be used
duced cardiac output with peripheral hypoperfusion (Table 12.2). as an extension of the clinical examination in the first instance
Since the sensitivity and specificity of symptoms and signs are often where available. Repeated echocardiography is usually not
not satisfactory, careful clinical evaluation needs to be followed by needed unless there is relevant deterioration in clinical status.
these additional investigations: Bedside thoracic ultrasound for signs of interstitial oedema and
2174 ESC Guidelines
Figure 12.2 Initial management of a patient with acute heart failure. aAcute mechanical cause: myocardial rupture complicating acute coronary
syndrome (free wall rupture, ventricular septal defect, acute mitral regurgitation), chest trauma or cardiac intervention, acute native or prosthetic
valve incompetence secondary to endocarditis, aortic dissection or thrombosis, see above.
ESC Guidelines 2175
AHF ¼ acute heart failure; BNP ¼ B-type natriuretic peptide; BUN ¼ blood urea nitrogen; ECG ¼ electrocardiogram; MR-proANP ¼ mid-regional pro A-type natriuretic
peptide; NT-proBNP ¼ N-terminal pro-B type natriuretic peptide; TSH ¼ thyroid-stimulating hormone
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
Recommendations for the management of patients with acute heart failure: oxygen therapy and ventilatory support
AHF ¼ acute heart failure; BiPAP ¼ bilevel positive airway pressure; COPD ¼ chronic obstructive pulmonary disease; CPAP ¼ continuous positive airway pressure; PaCO2 ¼
partial pressure of carbon dioxide in arterial blood; PaO2 ¼ partial pressure of oxygen in arterial blood; SpO2 ¼ transcutaneous oxygen saturation.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
In AHF, oxygen should not be used routinely in non-hypoxaemic pa- mortality rates,543 although data regarding mortality are less
tients, as it causes vasoconstriction and a reduction in cardiac out- conclusive. CPAP is a feasible technique in the pre-hospital
put.546,547 In COPD, hyperoxygenation may increase ventilation – setting, because it is simpler than pressure support positive
perfusion mismatch, suppressing ventilation and leading to hyper- end-expiratory pressure (PS-PEEP) and requires minimal training
capnia. During oxygen therapy, acid –base balance and transcutane- and equipment. On hospital arrival, patients who still show signs
ous SpO2 should be monitored. of respiratory distress should continue with non-invasive ventila-
Non-invasive positive pressure ventilation includes both CPAP tion, preferably PS-PEEP, in case of acidosis and hypercapnia, par-
and bi-level positive pressure ventilation (PPV). Bi-level PPV also al- ticularly in those with a previous history of COPD or signs of
lows inspiratory pressure support that improves minute ventilation fatigue.540
and is especially useful in patients with hypercapnia, most typically Caution should be exercised with regard to side effects of anaes-
COPD patients. thetic drugs, among which propofol can induce hypotension and
Congestion affects lung function and increases intrapulmonary have cardiodepressive side effects. In contrast, midazolam may
shunting, resulting in hypoxaemia. The fraction of inspired oxygen have fewer cardiac side effects and thus is preferred in patients
(FiO2) should be increased up to 100% if necessary, according to with AHF or cardiogenic shock.
SpO2, unless contraindicated. Hyperoxia, however, should be A management algorithm for patients with AHF based on
avoided.546,547 Non-invasive positive pressure ventilation reduces the clinical profile during an early phase is presented in
respiratory distress541 – 545 and may decrease intubation and Figure 12.3.
2178 ESC Guidelines
Figure 12.3 Management of patients with acute heart failure based on clinical profile during an early phase
a
Symptoms/signs of congestion: orthopnoea, paroxysmal nocturnal dyspnoea, breathlessness, bi-basilar rales, an abnormal blood pressure re-
sponse to the Valsalva maneuver (left-sided); symptoms of gut congestion, jugular venous distension, hepatojugular reflux, hepatomegaly, ascites,
and peripheral oedema (right-sided).
ESC Guidelines 2179
Pharmacological therapy
Recommendations for the management of patients with acute heart failure: pharmacotherapy
improve symptoms. It is recommended to regularly monitor symptoms, urine output, renal function and electrolytes during I C
use of i.v. diuretics.
In patients with new-onset AHF or those with chronic, decompensated HF not receiving oral diuretics the initial
Vasodilators
i.v. vasodilators should be considered for symptomatic relief in AHF with SBP >90 mmHg (and without symptomatic
537,
hypotension). IIa B
550–555
Symptoms and blood pressure should be monitored frequently during administration of i.v. vasodilators.
In patients with hypertensive AHF, i.v. vasodilators should be considered as initial therapy to improve symptoms and reduce 537,
IIa B
congestion. 551–554
Inotropic agents – dobutamine, dopamine, levosimendan, phosphodiesterase III (PDE III) inhibitors
Short-term, i.v. infusion of inotropic agents may be considered in patients with hypotension (SBP <90 mmHg) and/or signs/
IIb C
peripheral perfusion and maintain end-organ function.
An intravenous infusion of levosimendan or a PDE III inhibitor may be considered to reverse the effect of beta-blockade
IIb C
if beta-blockade is thought to be contributing to hypotension with subsequent hypoperfusion.
Inotropic agents are not recommended unless the patient is symptomatically hypotensive or hypoperfused because of
III A 556, 557
safety concern.
Vasopressors
A vasopressor (norepinephrine preferably) may be considered in patients who have cardiogenic shock, despite treatment
IIb B 558
with another inotrope, to increase blood pressure and vital organ perfusion.
It is recommended to monitor ECG and blood pressure when using inotropic agents and vasopressors, as they can cause 540,
I C
arrhythmia, myocardial ischaemia, and in the case of levosimendan and PDE III inhibitors also hypotension. 559–563
In such cases intra-arterial blood pressure measurement may be considered. IIb C
Thrombo-embolism prophylaxis
Thrombo-embolism prophylaxis (e.g. with LMWH) is recommended in patients not already anticoagulated and with no
I B 564
contra-indication to anticoagulation, to reduce the risk of deep venous thrombosis and pulmonary embolism.
Other drugs
d
IIa C
b. amiodarone may be considered. IIb B 565–567
Opiates may be considered for cautious use to relieve dyspnoea and anxiety in patients with severe dyspnoea but nausea
IIb B 568, 569
and hypopnea may occur.
AHF ¼ acute heart failure; ECG ¼ electrocardiogram; HF ¼ heart failure; i.v. ¼ intravenous; LMWH ¼ low molecular weight heparin; SBP ¼ systolic blood pressure.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
d
Beta-blockers should be used cautiously, if the patient is hypotensive.
2180 ESC Guidelines
a
Not available in many European countries.
ESC Guidelines 2181
12.3.4 Management of patients with cardiogenic shock 12.4 Management of evidence-based oral
Cardiogenic shock is defined as hypotension (SBP ,90 mmHg) des- therapies
pite adequate filling status with signs of hypoperfusion (Table 12.2).
The pathogenetic scenarios of cardiogenic shock range from low- Recommendations regarding oral evidence-based
output advanced end-stage chronic HF to acute-onset de novo disease-modifying therapies in patients with acute heart
cardiogenic shock most often caused by STEMI, but also by various failure
aetiologies other than ACS. A patient in cardiogenic shock should
undergo immediate comprehensive assessment. ECG and echocar-
Recommendations Class a Level b
diography are required immediately in all patients with suspected
cardiogenic shock. In patients with cardiogenic shock complicating In case of worsening of chronic HFrEF, every
attempt should be made to continue evidence-
ACS, an immediate coronary angiography is recommended (within based, disease-modifying therapies, in the I C
I C
Intravenous inotropic agents (dobutamine) may be considered to increase cardiac output. IIb C
Vasopressors (norepinephrine preferable over dopamine) may be considered if there is a need to maintain SBP in the
IIb B 558
presence of persistent hypoperfusion.
IABP is not routinely recommended in cardiogenic shock. III B 585, 586
Short-term mechanical circulatory support may be considered in refractory cardiogenic shock depending on patient age,
IIb C
comorbidities and neurological function.
ACS ¼ acute coronary syndrome; CCU ¼ coronary care unit; ECG ¼ electrocardiogram; IABP ¼ intra-aortic balloon pump; ICU ¼ intensive care unit; SBP ¼ systolic blood
pressure.
a
Class of recommendation.
b
Level of evidence.
c
Reference(s) supporting recommendations.
ESC Guidelines 2183
12.5 Monitoring of clinical status of † once provided with tailored education and advice about self-care.
patients hospitalized due to acute heart Patients should preferably be
failure † enrolled in a disease management programme; follow-up plans
must be in place prior to discharge and clearly communicated
Recommendations regarding monitoring of clinical to the primary care team;
status of patients hospitalized due to acute heart failure † reviewed by their general practitioner within 1 week of discharge;
† seen by the hospital cardiology team within 2 weeks of discharge
Recommendations Class a Level b if feasible.
Standard non-invasive monitoring of heart rate,
rhythm, respiratory rate, oxygen saturation and I C Patients with chronic HF should be followed up within a multipro-
blood pressure is recommended. fessional HF service. Pre- and post-discharge management should
13. Mechanical circulatory support for patients receiving ECMO for refractory cardiogenic shock
(online calculator at http://www.save-score.com).594
and heart transplantation In addition, MCS systems, particularly ECLS and ECMO, can be
used as a ‘bridge to decision’ (BTD) in patients with acute and rap-
13.1 Mechanical circulatory support idly deteriorating HF or cardiogenic shock to stabilize haemo-
For patients with either chronic or acute HF who cannot be stabi- dynamics, recover end-organ function and allow for a full clinical
lized with medical therapy, MCS systems can be used to unload the evaluation for the possibility of either heart transplant or a more
failing ventricle and maintain sufficient end-organ perfusion. Patients durable MCS device.595
in acute cardiogenic shock are initially treated with short-term as- Evidence regarding the benefits of temporary percutaneous MCS
sistance using extracorporeal, non-durable life support systems so in patients not responding to standard therapy, including inotropes,
that more definitive therapy may be planned. Patients with chronic, is limited. In a meta-analysis of three randomized clinical trials
Table 13.2 INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) stages for classifying
patients with advanced heart failure
ECLS ¼ extracorporeal life support; ECMO ¼ extracorporeal membrane oxygenation; INTERMACS ¼ Interagency Registry for Mechanically Assisted Circulatory Support;
LVAD ¼ left ventricular assist device; NYHA ¼ New York Heart Association.
a
Kaplan-Meier estimates with standard error of the mean for 1 year survival with LVAD therapy. Patients were censored at time of last contact, recovery or heart transplantation.
Due to small numbers outcomes for INTERMACS levels 5, 6, 7 were combined610.
for longer-term outcomes. Among patients with continuous-flow INTERMACS class, although the majority of VAD implants are
LVADs, actuarial survival is 80% at 1 year and 70% at 2 years in pre- done at INTERMACS levels 1 – 3.604,610 Additionally, it needs to
dominantly non-transplant-eligible patients. Notably, survival of be remembered that no RCTs exist comparing medical therapy
85% at 2 years was recorded for patients up to 70 years of age with- vs. MCS devices in these transplant-eligible patients (Table 13.2).
out diabetes, renal impairment or cardiogenic shock.601,602 Patients Typically, patients with end-stage HF considered for MCS exhibit
receiving LVAD devices as BTT have a post-transplant survival rate many clinical hallmarks of declining cardiovascular function593 and
similar or better than those not requiring or receiving bridging.599 may already be on continuous inotropic support or manifest a de-
Despite technological improvements, bleeding, thromboembolism cline in end-organ function. Markers of liver and renal dysfunction,
(both of which can cause stroke), pump thrombosis, driveline infec- haematologic and coagulation abnormalities and lower serum albu-
tions and device failure remain significant problems and affect the min levels are associated with worse outcome.611,612
long-term outcome of patients on MCS. 599,603 – 606 It is recom- Evaluation of RV function is crucial since postoperative RV failure
mended that such devices should only be implanted and managed greatly increases perioperative mortality and reduces survival to,
at centres with appropriately trained specialist HF physicians and and after, transplantation. There are, however, multiple approaches
surgeons and an outpatient LVAD clinic with trained nursing staff.607 to assessment of the RV (see Section 5.2.3). If RV failure is expected
In some patients, LV reverse remodelling and functional improve- to be potentially reversible, temporary (days to weeks) extracor-
ment during MCS may permit removal of the LVAD [‘bridge to re- poreal right ventricular assist device (RVAD) support using a centri-
covery’ (BTR)]. This outcome is more likely in younger patients with fugal pump in addition to LVAD implantation may be considered.
an acute fulminant but reversible cause of HF, such as acute myocar- For patients with chronic biventricular failure or a high risk for per-
ditis or peripartum cardiomyopathy.608,609 LVADs may also be used sisting RV failure after LVAD implantation, implantation of a biven-
as a ‘bridge to candidacy’ (BTC) in order to permit recovery of tricular assist device (BiVAD) may be necessary. Patients requiring
end-organ dysfunction, improve RV function and relieve pulmonary long-term BiVAD support must be transplant-eligible, as BiVAD
hypertension, which may allow initially ineligible patients to become therapy is not suitable for destination therapy. The outcomes of Bi-
eligible for heart transplantation. VAD therapy are inferior to those for LVAD therapy and therefore
Earlier ventricular assist device (VAD) implantation in less severe- the indication for VAD therapy should be discussed before RV func-
ly ill patients, e.g. those not yet on inotropic support, was tested in a tion deteriorates. The implantation of a total artificial heart with re-
recent trial that revealed better outcomes than in those patients moval of the native heart should be restricted to selected patients
continuing on medical therapy.605 The INTERMACS registry like- who cannot be treated with an LVAD (unrepairable ventricular sep-
wise shows better outcomes in patients implanted with a higher tal defect, cardiac rupture).
2186 ESC Guidelines
Table 13.3 Patients potentially eligible for Table 13.4 Heart transplantation: indications and
implantation of a left ventricular assist device contra-indications
Patients with >2 months of severe symptoms despite optimal Patients to End-stage HF with severe symptoms, a poor prognosis,
medical and device therapy and more than one of the following: consider and no remaining alternative treatment options.
Motivated, well informed, and emotionally stable.
LVEF <25% and, if measured, peak VO2 <12 mL/kg/min.
Capable of complying with the intensive treatment
≥3 HF hospitalizations in previous 12 months without an obvious required postoperatively.
precipitating cause.
Contra- Active infection.
Dependence on i.v. inotropic therapy. indications Severe peripheral arterial or cerebrovascular disease.
Progressive end-organ dysfunction (worsening renal and/or hepatic Pharmacologically irreversible pulmonary hypertension
(LVAD should be considered with a subsequent re-
HF ¼ heart failure; HFrEF ¼ heart failure with reduced ejection fraction; ICD ¼
The use of mechanical circulatory support, particularly LVAD, implantable cardioverter-defibrillator; LVEF ¼ left ventricular ejection fraction,
should be considered for patients with potentially reversible or IN-TIME ¼ Implant-based multiparameter telemonitoring of patients with heart failure.
a
Class of recommendation.
treatable co-morbidities, such as cancer, obesity, renal failure, b
Level of evidence.
tobacco use and pharmacologically irreversible pulmonary c
Reference(s) supporting levels of evidence.
hypertension, with a subsequent re-evaluation to establish
candidacy.
14.1 Organization of care
The goal of management of HF is to provide a ‘seamless’ system of
14. Multidisciplinary team care that embraces both the community and hospital throughout
the health care journey. The standards of care that patients with HF
management should expect have been published by the ESC HFA.591 To achieve
Non-pharmacological non-device/surgical interventions used in the this goal, other services, such as cardiac rehabilitation and palliative
management of HF (both HFrEF and HFpEF) are summarized in care, must be integrated into the overall provision for patients with
Tables 14.1 and 14.2 and detailed practical recommendations on HF. Fundamental to the delivery of this complete package of care
their use have been published by the HFA of the ESC.591,592 There are multidisciplinary management programmes designed to improve
is no evidence that these on their own improve mortality, morbidity outcomes through structured follow-up with patient education, opti-
or quality of life. For this reason, these interventions have not been mization of medical treatment, psychosocial support and improved
given a recommendation with an evidence level. The exceptions are access to care (Table 14.1). Such strategies reduce HF hospitalization
implementation of care in a multidisciplinary framework, monitoring and mortality in patients discharged from the hospital.624,625
and exercise training (see recommendations table), all of which are Key to the success of these programmes is coordination of care
discussed below. along the continuum of HF and throughout the chain of care
2188 ESC Guidelines
Table 14.2 Key topics and self-care skills to include in patient education and the professional behaviours to optimize
learning and facilitate shared decision making
continued
ESC Guidelines 2189
Table 14.2 Key topics and self-care skills to include in patient education and the professional behaviours to optimize
learning and facilitate shared decision making (continued)
delivered by the various services within the health care system. This exercise tolerance, health-related quality of life and HF hospitaliza-
necessitates close collaboration between HF practitioners (primar- tion rates in patients with HF. A single large RCT618 showed a modest
ily cardiologists, HF nurses and general practitioners) and other ex- and non-significant reduction in the primary composite outcome of
perts, including pharmacists, dieticians, physiotherapists, all-cause mortality or all-cause hospitalization. There was no reduc-
psychologists, palliative care providers and social workers. The con- tion in mortality and no safety concerns were raised.618,633 The
tent and structure of HF management programmes may vary in dif- most recent Cochrane review of exercise training619 included 33
ferent countries and health care settings. The components shown in trials with 4740 patients with HF (predominantly HFrEF). There
Table 14.1 are recommended. HF services should be easily access- was a trend towards a reduction in mortality with exercise in trials
ible to the patient and his/her family and care providers. A telephone with .1 year of follow-up. Compared with the control group, exer-
helpline may facilitate access to professional advice. cise training reduced the rate of overall and HF-specific hospitaliza-
The website http://ww.heartfailurematters.org is an option for tion and improved quality of life. Practical recommendations on
professional information for those patients and families with Inter- exercise training have been published by the HFA.120
net access. There is evidence that in patients with HFpEF, exercise training has
several benefits, including improvements in exercise capacity, as mea-
14.2 Discharge planning sured objectively using peak oxygen consumption, quality of life and
Early readmission after hospital discharge is common and may be ad- diastolic function, assessed by echocardiography.321,620,621,634
dressed through coordinated discharge planning. The standards of Patients with HF, regardless of LVEF, are recommended to perform
care that patients should expect have been published by the HFA properly designed exercise training (see the recommendations table).
and the Acute Cardiac Care Association.540,631 Discharge planning
should commence as soon as the patient’s condition is stable. During 14.5 Follow-up and monitoring
hospital admission, providing patients with information and education Patients with HF benefit from regular follow-up and monitoring of
for self-care improves outcome. Discharge should be arranged for biomedical parameters to ensure the safety and optimal dosing of
when the patient is euvolaemic and any precipitants of the admission medicines and detect the development of complications or disease
have been treated. Hospitals with early physician follow-up after dis- progression that may require a change in management (e.g. the onset
charge show reduced 30-day readmission, and those that initiated of AF or development of anaemia). Monitoring may be undertaken by
programmes to discharge patients with an outpatient follow-up ap- the patients themselves during home visits, in community or hospital
pointment already scheduled experienced a greater reduction in clinics, by remote monitoring with or without implanted devices or
readmissions than those not taking up this strategy.632 by structured telephone support (STS). The optimal method of mon-
itoring will depend on local organizations and resources and will vary
14.3 Lifestyle advice among patients. For example, more frequent monitoring will be re-
There is little evidence that specific lifestyle advice improves quality quired during periods of instability or optimization of medication.
of life or prognosis; however, providing this information has become Older adults may also benefit from more frequent monitoring.
a key component of education for self-care. Patients should be pro- Some patients will be keen and able to participate in self-monitoring.
vided with sufficient up-to-date information to make decisions on High circulating NPs predict unfavourable outcomes in patients
lifestyle adjustment and self-care. Ideally for those patients admitted with HF, and a decrease in NP levels during recovery from circula-
to the hospital, lifestyle advice should begin prior to discharge. Infor- tory decompensation is associated with a better prognosis.588 – 590
mation should be individually tailored to need and take into account Although it is plausible to monitor clinical status and tailor treatment
relevant co-morbidities that may influence retention of information based on changes in circulating NPs in patients with HF, published
(such as cognitive impairment and depression). Practical recommen- studies have provided differing results.635 – 638 This does not enable
dations have been published by the HFA.591 Key topics to include us to recommend a broad application of such an approach.
are recommended in Table 14.2. Telemedicine in HF, which is also termed remote patient manage-
ment, has variable clinical trial results.639 Several meta-analyses sug-
14.4 Exercise training gest clinical benefits, but numerous prospectively initiated clinical
Several systematic reviews and meta-analyses of small studies have trials including .3700 patients have not confirmed this. These clin-
shown that physical conditioning by exercise training improves ical trials include Tele-HF,640 TIM-HF,641 INH,642 WISH643 and
2190 ESC Guidelines
14.7 Palliative and end-of-life care Advanced care planning, taking account of preferences for place of
death and resuscitation (which may include deactivating devices, such as
Palliative care approaches include a focus on symptom management,
emotional support and communication between the patient and his/
her family. Ideally this should be introduced early in the disease trajec-
tory and increased as the disease progresses. A decision to alter the
focus of care from modifying disease progression to optimising quality approach, is required in order to address and optimally coordinate
of life should be made in discussion with the patient, cardiologist, the patient’s care. Recent pilot studies have suggested an improve-
nurse and general practitioner. The patient’s family should be involved ment in symptom burden and quality of life,653,655 but these data are
in such discussions if requested by the patient652,653 (Table 14.4). too limited to provide a recommendation.
Key components of a palliative care service are recommended in Specific therapies and actions may provide palliation of symptoms
Table 14.5. Palliative care has been discussed in detail in a position and improve quality of life but have a limited evidence base:
paper from the ESC HFA.654
Liaison between the specialist palliative care services and the HF † Morphine (with an antiemetic when high doses are needed) can
team and/or the primary care physician, using a shared care be used to reduce breathlessness, pain and anxiety.656
ESC Guidelines 2191
† Increasing the inspired oxygen concentration may provide relief † Targeted therapies for specific aetiologies of HFrEF (e.g. myo-
of dyspnoea. carditis, peripartum cardiomyopathy)
† Diuretic management can be used to relieve severe congestion † Therapies directly improving cardiomyocyte function (e.g.
or optimize symptom control (congestion and thirst). acto-myosin cross-bridge activation, sarco/endoplasmic re-
† Reduce HF drugs that reduce blood pressure to maintain suffi- ticulum Ca2+-ATPase activation, ryanodine receptor stabiliza-
cient oxygenation and reduce the risk of falls. tion, energetic modulation) or targeting non-myocytic
compartment (e.g. anti-fibrosis/matrix remodelling)
Ideally these therapies should be delivered in the patient’s home. In the
† Therapies for HFmrEF/HFpEF (ARNIs, beta-blockers, soluble
majority of cases the whole family should receive social support.652
guanyl cyclase inhibitors, i.v. iron)
A management plan should be developed through discussion with
the patient and family. It should include 4. Devices and interventions
† Evaluate the comparative clinical effectiveness and cost- † Treatment algorithms for patients with HF excluded by pivotal
effectiveness of different strategies to screen for HF. clinical trials
† Palliative and end-of-life care management and assessment of
3. Pharmacological therapy
outcome
† Identification of non-responders to current guideline-advised † Optimal integration of multidisciplinary care, self-management
medical treatment of patients and their adherence.
2192 ESC Guidelines
Recommendations for cardiac imaging in patients with suspected or established heart failure Class a Level b
TTE is recommended for the assessment of myocardial structure and function in subjects with suspected HF in order to establish a
I C
diagnosis of either HFrEF, HFmrEF or HFpEF.
TTE is recommended for the assessment of LVEF in order to identify patients with HF who would be suitable for evidence-based
I C
pharmacological and device (ICD, CRT) treatment recommended for HFrEF.
Recommendations aiming to prevent or delay the development of overt heart failure or prevent death Class a Level b
before the onset of symptoms
CRT is recommended for symptomatic patients with HF in sinus rhythm with a QRS duration ≥150 msec and LBBB QRS morphology and
I A
with LVEF ≤35% despite OMT in order to improve symptoms and reduce morbidity and mortality.
CRT is recommended for symptomatic patients with HF in sinus rhythm with a QRS duration of 130–149 msec and LBBB QRS
I B
morphology and with LVEF ≤35% despite OMT in order to improve symptoms and reduce morbidity and mortality.
CRT rather than RV pacing is recommended for patients with HFrEF regardless of NYHA Class who have an indication for ventricular
I A
continued
ESC Guidelines 2193
Adaptive servo-ventilation is not recommended in patients with HFrEF and a predominant central sleep apnoea because of an
III B
increased all-cause and cardiovascular mortality.
Thiazolidinediones (glitazones) are not recommended in patients with HF, as they increase the risk of HF worsening and HF hospitalization. III A
NSAIDs or COX-2 inhibitors are not recommended in patients with HF, as they increase the risk of HF worsening and HF hospitalization. III B
Recommendations regarding diagnostic measurements in patients with suspected acute heart failure Class a Level b
Upon presentation a measurement of plasma natriuretic peptide level (BNP, NT-proBNP or MR-proANP) is recommended in all
Recommendations for the management of patients with acute heart failure – pharmacotherapy Class a Level b
I C
symptoms. It is recommended to regularly monitor symptoms, urine output, renal function and electrolytes during use of i.v. diuretics.
In patients with new-onset AHF or those with chronic, decompensated HF not receiving oral diuretics the initial recommended dose
should be 20–40 mg i.v. furosemide (or equivalent); for those on chronic diuretic therapy, initial i.v. dose should be at least equivalent to I B
oral dose.
It is recommended to give diuretics either as intermittent boluses or a continuous infusion, and the dose and duration should be
I B
adjusted according to the patients’ symptoms and clinical status.
Inotropic agents are not recommended unless the patient is symptomatically hypotensive or hypoperfused because of safety concern. III A
a
Recommendations regarding management of patients with cardiogenic shock Class Level b
In all patients with suspected cardiogenic shock, immediate ECG and echocardiography are recommended. I C
All patients with cardiogenic shock should be rapidly transferred to a tertiary care centre which has a 24/7 service of cardiac
I C
catheterization, and a dedicated ICU/CCU with availability of short-term mechanical circulatory support.
Recommendations regarding oral evidence-based disease-modifying therapies in patients with acute heart failure Class a Level b
In case of worsening of chronic HFrEF, every attempt should be made to continue evidence-based, disease-modifying therapies, in the
I C
absence of haemodynamic instability or contra-indications.
Recommendations for exercise, multidisciplinary management, and monitoring of patients with heart failure Class a Level b
It is recommended that regular aerobic exercise is encouraged in patients with HF to improve functional capacity and symptoms. I A
It is recommended that regular aerobic exercise is encouraged in stable patients with HFrEF to reduce the risk of HF hospitalization. I A
It is recommended that patients with HF are enrolled in a multidisciplinary care management programme to reduce the risk of HF
I A
hospitalization and mortality.
ACE-I ¼ angiotensin-converting enzyme inhibitor; AHF ¼ acute heart failure;; ARB ¼ angiotensin receptor blocker; AST ¼ aspartate aminotransferase; AV ¼ atrio-ventricular;
BNP ¼ B-type natriuretic peptide; CCU ¼ coronary care unit; COX-2 ¼ cyclooxygenase 2; CRT ¼ cardiac resynchronization therapy; CT ¼ computed tomography; DCM ¼
dilated cardiomyopathy; ECG ¼ electrocardiogram; HF ¼ heart failure; HFmrEF ¼ heart failure with mid-range ejection fraction; HFpEF ¼ heart failure with preserved ejection
fraction; HFrEF ¼ heart failure with reduced ejection fraction; ICD ¼ implantable cardioverter-defibrillator; ICU ¼ intensive care unit; i.v. ¼ intravenous; LBBB ¼ left bundle
branch block; LV ¼ left ventricular; LVEF ¼ left ventricular ejection fraction; MI ¼ myocardial infarction; MRA ¼ mineralocorticoid receptor antagonist; MR-proANP ¼ mid-
regional pro A-type natriuretic peptide; NSAIDs ¼ non-steroidal anti-inflammatory drugs; NT-proBNP ¼ N-terminal pro-B type natriuretic peptide; NYHA ¼ New York Heart
Association; OMT ¼ optimal medical therapy; QRS ¼ Q, R, and S waves (combination of three of the graphical deflections); RV ¼ right ventricular; TTE ¼ transthoracic
echocardiography.
a
Class of recommendation.
b
Level of evidence
c
Or ARB if ACEI is not tolerated/contra-indicated.
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