Cardio-Renal Protection Through Renin–Angiotensin–Aldosterone System Inhibition
acute heart failure:therapeutic update
1.
2. Algorithm for management of acute heart failure
Current therapeutic strategies
Novel therapeutic strategies
Newer inotropic drugs
New Recommendations for the Hospitalized Patient
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
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.
18.
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.
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
