Inotropes - still an option? - ESC | Congresses

38 Pages·2012·1.4 MB·English

Inotropes for the management of
AHF- still an option?
Dr John T Parissis
Attikon University Hospital
Athens, Greece
Disclosures:
- ALARM investigator received
research grants by Abbott US and Orion Pharma
- Co-PI in LEVOREP trial supported by Orion Pharma
Conventional Treatments of
Acute Heart Failure
Reduce Decrease Augment
fluid preload contrac-
volume and/or tility
afterload
IV Diuretics Vasodilators Inotropes
Reduce Volume Decrease Preload Augment
Overload and Afterload Contractility
Nitroglycerin Dobutamine
Nitroprusside Levosimendan
Loop Diuretics
Nesiritide Milrinone
Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7–S12.
Established and investigational
inotropic agents
Inotropic mechanism Drugs

Currently used
Sodium-potassium-ATPase inhibition Digoxin

Beta-Adrenoceptor stimulation Dobutamine, dopamine

Phosphodiesterase inhibition Enoximone, milrinone

Calcium sensitization Levosimendan


Investigational

Sodium-potassium-ATPase inhibition Istaroxime

plus SERCA activation
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


Eur Heart J, 2011:32;1838–1845
Istaroxime
Levosimendan
Stevenson, Circulation 2003;108:367-372
Patient profiles for inotropic therapy
Hemodynamic impairment with low cardiac output (i.e. CI <

2.0 Lt/min/m2) and increased left and/or right ventricular filling
pressures [i.e. PCWP (18–20 mmHg) and RAP (10–12
mmHg)].

Critical patient’s conditions caused by abnormal

hemodynamics and including any of the following:
a. Severe exercise limitation
b. Diuretic resistant fluid overload
c. Kidney and/or liver dysfunction as shown by abnormal
laboratory exams (serum creatinine, BUN, bilirubin,etc.)
Teerlink J, Metra M, et al. Heart Fail Rev 2009;14:243–253
Limitations of traditional inotropic
agents
Tachyarrhythmias

Increased ventricular arrhythmias
Increased ventricular rate in atrial fibrillation
Myocardial ischemia

Hypotension—coronary hypoperfusion
Increased heart rate and myocardial contractility-
increased myocardial oxygen consumption
Direct myocyte toxicity-intracellular calcium

overload
ESC guidelines 2012 on diagnosis
and treatment of AHF
An i.v. infusion of an inotrope (e.g. dobutamine) should be

considered in patients with hypotension and/or hypoperfusion to
increase cardiac output, increase blood pressure, and improve
peripheral perfusion. The ECG should be monitored continuously
because inotropic agents can cause arrhythmias and myocardial
ischaemia.
Recommendation: IIa Level of Evidence : C

An i.v. infusion of levosimendan (or a phosphodiesterase inhibitor)

may be considered to reverse the effect of beta-blockade if beta-
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.
Recommendation: IIb Level of Evidence : C

McMurray JJ, et al. Eur Heart J. 2012;33(14):1787-847
Parissis et al. Curr Opin Crit Care 2010;16:432-41
Drug Therapy in AHF
Overall use of AHF therapies: IV diuretics, vasodilators, Driven by
inotropes and levosimendan: by All AHF vs. top 3 AHF Classifications Cardiogenic
100% 95% Shock
90% sub-group
87%
90%
84%
81%
80%
70%
60%
52%
50%
42%
39% 39%
40%
35%
32% 31%
30%
20%
9%
7%
10% 6% 6%
0%
All AHF ADHF Pulmonary Oedema Cardiogenic shock
IV diuretics IV vasodilators IV inotropes *Levosimendan
Sample = 4,953 ALARM-HF patients
Follath F, Yilmaz B, Delgado J, Parissis J,…, Mebazaa A. Intensive Care Med. 2011;37(4):619-26
Inotropes: Dobutamine Is the Most Frequently
Used Drug Across All AHF Indications (58%)
70%
63%
58%
60% 56% 56%
50%
38%
40%
34% 35%
33%
30%
30%
19% 22%
20% 17% 17%
15%
12%
11%
10%
4%
3% 3% 3%
0%
All AHF ADHF P-OE Cardio shock
DOBUTAMINE DOPAMINE LEVOSIMENDAN NOREP/EPINEPH PDE INHIB
Sample = All IV Inotropes patients 1,910, ADHF 620, P-OE 629 , Cardio shock 469
Follath F, Yilmaz B, Delgado J, Parissis J,…, Mebazaa A. Intensive Care Med. 2011;37(4):619-26