This document provides guidelines for the management of acute heart failure. It discusses current treatment strategies including diuretics, vasodilators, and inotropes. Novel therapeutic strategies are mentioned, such as newer inotropic drugs, rollofylline, tolvaptan, ularitide, relaxin, and others. The goals of therapy for acute heart failure are to make the patient feel better by reducing dyspnea, improve quality of life, reduce mortality and rehospitalization, and do so safely. Recent large clinical trials of new agents for acute heart failure have failed to show benefits observed in smaller earlier studies.

2. Algorithm for management of acute heart failure
Current therapeutic strategies
Novel therapeutic strategies
Newer inotropic drugs
New Recommendations for the Hospitalized Patient

3. Acute heart failure is a heterogeneous syndrome with multiple presentations

4. 3%
50%
47%
Suggested initial triage in patients with suspected AHF syndromes

5. Suggested treatment algorithm for patients with hypertensive AHF syndromes.

6. Suggested treatment algorithm for patients with normotensive AHF syndromes.

7. Suggested treatment algorithm for patients with hypotensive AHF syndromes.

8. What Should be the Goals of Therapy
of AHF?
• Make the patient feel better:
reduce dyspnea and improve QOL
• Reduce Mortality
• Reduce Rehospitalization
• Do it safely

9. Various targets for therapies used in the management
of acute heart failure.

10. Current Treatment of Acute Heart Failure
Use in ADHERE Registry
88%
21
Diuretics
Vasodilators
Reduce
Fluid
Volume
Decrease
Preload
and/or
Afterload
(Na+&H20)
15%
Inotropes
Augment
Contractility

11. Vasodilators
Loop diuretics
Used
in 88%
of cases
10%
1%
10%
Inotropics
6%
6%
3%
?

12. Novel therapeutic targets for the
treatment of acute heart failure

13. Sites of action of drugs producing diuresis and natriuresis.
Rolofylline
Tolvaptan

14. Sites of action of vasodilators.
Ularitide
Relaxin
Nesiritide

15. Sites of action of inotropic agents.
Istaroxime
Levosimendan
Omecamtiv
mecarbil

16. Why do new agents fail in Phase III trials?
In recent years a repeated finding, particularly in clinical trials of patients with
AHF, is that the positive results that are observed in preclinical and Phase II
studies are not confirmed in large Phase III RCTs.

17. A Word About Inotropes.
In the setting of AHF, inotropic agents are only
recommended in patients with SBP 90 mmHg and
evidence of inadequate organ perfusion despite other
therapeutic interventions.

19. Issues with Current Inotropes
Initial choice of therapy
Weaning
Patient related variables
Differences in efficacy
Adverse effect profile
Survival data
“Long-term” infusions
There is an urgent clinical need for agents that improve cardiac performance
with a favourable safety profile.

20. Inotropic mechanisms and drugs
Inotropic mechanism
Drugs
Sodium-potassium-ATPase inhibition
Digoxin
b-Adrenoceptor stimulation
Dobutamine, dopamine
Phosphodiesterase inhibition
Enoximone, milrinone
Calcium sensitization
Levosimendan
Sodium-potassium-ATPase inhibition
plus SERCA activation
Istaroxime
Acto-myosin cross-bridge activation
Omecamtiv mecarbil
SERCA activation
Gene transfer
SERCA activation plus vasodilation
Nitroxyl donor;
CXL-1020
Ryanodine receptor stabilization
Ryanodine receptor
stabilizer; S44121
Energetic modulation
Etomoxir, pyruvate

21. Results of the recent AHF trials
(disappointing)
Study
Patients
Primary End Point
Calcium Sensitizer (Levosimendan)
LIDO
CASINO
203
299
REVIVE II
600
SURVIVE
800
Change CI 24 h and PCWP 24 h
Mortality 30 d and Mortality
180 d
Composite global assess. at
6 h, 24 h 5 d
Mortality 180 d
SERCA agonist & Na/K ATPase inhibitor (Istaroxime)
HORIZON-HF
120
PCWP Changes from baseline

22. ATOMIC-AHF (Acute Treatment with
Omecamtiv Mecarbil to Increase
Contractility in Acute Heart Failure)
ESC Congress 2013 in Amsterdam

23. Calcium sensitizers
Levosimendan (Simdax®) increases
sensitivity of troponin in the heart
to calcium. This results in increased
myocardial contractility. It is infused
i.v. for short treatment of AHF.

24. Levosimendan :
ESC Guidelines 2012
Patients with hypotension, hypoperfusion or shock
An i.v. infusion of levosimendan
(or a phosphodiesterase inhibitor) may be considered
to reverse the effect of ẞ
-blockade if ẞ
-blockade is
thought to be contributing to hypoperfusion.
• The ECG should be monitored continuously because inotropic agents
can cause arrhythmias and myocardial ischaemia,
• and, as these agents are also vasodilators, blood pressure should be
monitored carefully.
Class of recommendation IIb . Level of evidence C

25. New Recommendations for the Hospitalized Patient
2013 ACCF/AHA Guideline for the Management of Heart Failure
A Report of the American College of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines

26. The Major Reason for Heart Failure Hospitalizations
Worsening chronic
heart failure (75%)
De novo heart
failure (23%)
Advanced/ end-stage
heart failure (2%)
Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21
Cleland JG et al. Eur Heart J. 2003; 24: 442

27. Therapies in the Hospitalized HF Patient
Recommendation
HF patients hospitalized with fluid
overload should be treated with
intravenous diuretics
HF patients receiving loop diuretic
therapy, should receive an initial New
parenteral dose greater than or equal to
their chronic oral daily dose, then should
be serially adjusted
COR LOE
I
B
I
B

28. Therapies in the Hospitalized HF Patient
Recommendation
When diuresis is inadequate, it is
New
reasonable to
a) Give higher doses of intravenous loop
diuretics; or
b) add a second diuretic (e.g., thiazide)
COR LOE
IIa
B

29. Therapies in the Hospitalized HF Patient
Recommendation
COR
LOE
Low-dose dopamine infusion may be considered
with loop diuretics to improve diuresis New
IIb
B
Ultrafiltration may be considered for patients
with refractory congestion
New
IIb
C
Intravenous nitroglycerin, nitroprusside or
nesiritide may be considered an adjuvant to
diuretic therapy for stable patients with HF
IIb
A
New

30. Therapies in the Hospitalized HF Patient
Recommendation
COR LOE
HFrEF patients requiring HF
hospitalization on GDMT should continue
GDMT unless hemodynamic instability or
contraindications
New
I
B
Initiation of beta-blocker therapy at a low
dose is recommended after optimization of
volume status and discontinuation of
intravenous agents
I
B
New

31. Recommendations for Inotropic Support
Recommendations
Cardiogenic shock pending New
definitive therapy or resolution
Short-term support for threatened
end-organ dysfunction in
hospitalized patients with
stage D and severe HFrEF New
Short-term intravenous use in
hospitalized patients without
evidence of shock or
threatened end-organ performance
is potentially harmful
New
COR
LOE
I
C
IIb
B
III:
Harm
B