ESC Guidelines Page 21 of 85

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 30, 2016

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.
 Überaktivierung von RAAS und SNS bei HFrEF:
Pathomechanismus + Basis bisheriger Therapiestrategien

Sympathisches
Nervensystem β-Blocker

Adrenalin α1, β1, β2

Noradrenalin Rezeptoren

Vasokonstriktion
RAAS-Aktivität
Natriuretisches Peptid- HFrEF- Vasopressin
Herzfrequenz
system SYMPTOME &
Kontraktilität
PROGRESSION
NP-Rezeptoren Natriuretische Peptide (NP)

Vasodilatation
Blutdruck RAAS-Hemmer
Sympathikotonus RAAS (ACEI, ARB, MRA)
Natriurese/Diurese
Vasopressin Ang II AT1Rezeptor
Aldosteron
Fibrose Vasokonstriktion
Hypertrophie Blutdruck
Sympathikotonus
Aldosteron
Hypertrophie
Fibrose

 Die kritische Bedeutung des RAAS wird durch die günstigen Wirkungen von ACEI, ARB und MRA gestützt1
 Nutzen von β-Blockern weist darauf hin, dass das SNS ebenfalls eine Schlüsselrolle spielt1

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

1 Referenzen der Abbildungen: Levin et al. N Engl J Med 1998;339;321–8; Nathisuwan & Talbert. Pharmacotherapy
2002;22:27–42; Kemp & Conte. Cardiovasc Pathol 2012;365–371; Schrier & Abraham. N Engl J Med 1999;341:577-85
Sacubitril/Valsartan inhibiert gleichzeitig Neprilysin und AT1-Rezeptoren

Sacubitril /
ANP, BNP, CNP, andere
Valsartan
vasoaktive Peptide (LCZ696)
RAAS
Angiotensinogen
(Freisetzung in Leber)
Sacubitril
(AHU377; Prodrug)
Ang I

Inaktive LBQ657 Ang II

Fragmente
(Neprilysin-Inhibitor) Valsartan

AT1-Rezeptor
 Verstärkung  Hemmung
Vasorelaxation Vasokonstriktion
 Blutdruck  Blutdruck
 Sympathikotonus
 Sympathikotonus
 Aldosteronspiegel
 Fibrose  Aldosteron
 Hypertrophie  Fibrose
 Natriurese/Diurese  Hypertrophie

Levin et al. N Engl J Med 1998;339;321–8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27–42;
2 Schrier & Abraham N Engl J Med 1999;341:577–85; Langenickel & Dole. Drug Discovery Today: Ther
Strateg 2012;9:e131–9; Feng et al. Tetrahedron Letters 2012;53:275–6
PARADIGM-HF: Studiendesign

Randomisierung
Doppelblinde
n=8.442
Behandlungsphase
Einfach blinde aktive
Run-in-Phase

Sacubitril/Valsartan 2 x 200 mg
Enalapril Sacubitril/Val Sacubitril/Val
2 x 10 mg* 2 x 100 mg 2 x 200 mg

Enalapril 2 x 10 mg

2 Wochen 1-2 Wochen 2-4 Wochen Follow-up (median 27 Monate)

Zusätzlich zur HFrEF-Standardtherapie (ausgenommen ACEI und ARB)

*Enalapril 2 x 5 mg über 1–2 Wochen gefolgt von Enalapril 2 x 10 mg als optionale Eingangsdosis für Patienten, die mit ARB oder mit
einem niedrig dosiertem ACEI behandelt werden.
3 McMurray et al. Eur J Heart Fail 2013;15:1062–73; McMurray et al. Eur J Heart Fail 2014;16:817–25;
McMurray et al. N Engl J Med 2014;371(11):993-1004.
Primärer Endpunkt: CV-bedingter Tod oder
erste Hospitalisierung wg. Herzinsuffizienz

1,0 Enalapril
Sacubitril/Valsartan (LCZ696)
Wahrscheinlichkeit

0,6
Kumulative

Hazard Ratio = 0,80 [95% CI: 0,73 - 0,87)

p<0,001 [p=0,0000002]
0,4 Absolute Risikoreduktion: 4,7%, NNT=21

0,2

0
0 180 360 540 720 900 1080 1260
Tage seit der Randomisierung
Anz. mit Risiko
Sacubitril-Vals. 4.187 3.922 3.663 3.018 2.257 1.544 896 249
Enalapril 4.212 3.883 3.579 2.922 2.123 1.488 853 236

4
McMurray et al. N Engl J Med 2014;371(11):993-1004.
The Do`s and Don`ts of CRT

NO Yes

LBB morphology
Non- LBB morphology

Ruschitzka HFA 2016

mod. Cleland EHJ 2013
/
Page 44 of 85 ESC Guidelines

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 30, 2016

Figure 12.1 Clinical profiles of patients with acute heart failure based on the presence/absence of congestion and/or hypoperfusion

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
Page 50 of 85 ESC Guidelines

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 30, 2016

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).
 European Heart Journal Advance Access published May 20, 2016

European Heart Journal ESC GUIDELINES

doi:10.1093/eurheartj/ehw128

2016 ESC Guidelines for the diagnosis and

treatment of acute and chronic heart failure
The Task Force for the diagnosis and treatment of acute and chronic
heart failure of the European Society of Cardiology (ESC)

Developed with the special contribution of the Heart Failure

Association (HFA) of the ESC

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 30, 2016

Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland),
Adriaan A. Voors* (Co-Chairperson) (The Netherlands), Stefan D. Anker (Germany),
Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK),
Volkmar Falk (Germany), José Ramón González-Juanatey (Spain), Veli-Pekka Harjola
(Finland), Ewa A. Jankowska (Poland), Mariell Jessup (USA), Cecilia Linde (Sweden),
Petros Nihoyannopoulos (UK), John T. Parissis (Greece), Burkert Pieske (Germany),
Jillian P. Riley (UK), Giuseppe M. C. Rosano (UK/Italy), Luis M. Ruilope (Spain),
Frank Ruschitzka (Switzerland), Frans H. Rutten (The Netherlands),
Peter van der Meer (The Netherlands)
Document Reviewers: Gerasimos Filippatos (CPG Review Coordinator) (Greece), John J. V. McMurray (CPG Review
Coordinator) (UK), Victor Aboyans (France), Stephan Achenbach (Germany), Stefan Agewall (Norway),
Nawwar Al-Attar (UK), John James Atherton (Australia), Johann Bauersachs (Germany), A. John Camm (UK),
Scipione Carerj (Italy), Claudio Ceconi (Italy), Antonio Coca (Spain), Perry Elliott (UK), Çetin Erol (Turkey),
Justin Ezekowitz (Canada), Covadonga Fernández-Golfı́n (Spain), Donna Fitzsimons (UK), Marco Guazzi (Italy),

* 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.
The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC
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
health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.
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.
& European Society of Cardiology 2016. All rights reserved. For permissions please email: journals.permissions@oup.com.