Notfall-/Intensivmedizin: akute Herzinsuffizienz Therapie ... Akute HI... · Diuretic Strategies in...
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Notfall-/Intensivmedizin: akute Herzinsuffizienz
Therapie der akuten Herzinsuffizienz
Echokardiographie Update 2013 München 14.- 15. Dezember 2013
S. Felix
Klinik für Innere Medizin B
Ernst-Moritz-Arndt-Universität Greifswald
Definition
Symptome
Prognose
Aktuelle Studienlage
Neue Pharmaka
Behandlung der akuten Herzinsuffizienz
Acute de novo heart failure
(e. g. acute myocardial infarction, myocarditis)
Acute acute decompensated (chronic) heart failure (ADHF)
Transition from chronic compensated to acute decompensated heart failure
Decompensated HF
Pulmonary oedema
Cardiogenic shock
Hypertensive HF
Right HF ESC Guidelines
Eur Heart J 2008; 29: 2388–2442
Worsening HF
De novo HF
End-stage HF
Gheorghiade et al.
J Am Coll Cardiol 2013;61:391–403
Acute Heart Failure
Definition
Symptome
Prognostische Faktoren
Aktuelle Studienlage
Neue Pharmaka
Behandlung der akuten Herzinsuffizienz
Gheorghiade et al. Eur J Heart Failure 2010; 12: 423–433
Abnormal LV function sytemic congestion →
0
10
20
30
40
50
60
70
80
90
100
Dyspnea RalesPeripheral Edema
%
From Adams et al. Am Heart J 2005;149:209-16
Adhere
AHF- Symptoms
DD
ADHF vs pulmon. disease
- ECG
- Chest x-ray
- NT-pro BNP ≥ 300 pg/mL
BNP ≥ 100 pg/ml
- ECHO
ESC Guidelines 2012
Mebazaa et al. Eur Heart J 2010; 31: 832–841
The impact of early standard therapy on dyspnoea in patients with AHF
URGENT-dyspnoea study
Gheorghiade et al.
EurJ Heart Failure
2010; 12: 423–433
Abnormal LV function systemic congestion →
Definition
Symptome
Prognose
Aktuelle Studienlage
Neue Pharmaka
Behandlung der akuten Herzinsuffizienz
EuroHeart Failure Survey II (2.981 AHF patients)
Harjola et al. Eur J Heart Failure 2010;12: 239–248
Definition
Symptome
Prognose
Aktuelle Studienlage
Neue Pharmaka
Behandlung der akuten Herzinsuffizienz
Clinical Trials in worsening HF/ADHF
Trial Agent Pts Effects on Effects on
Outcome Symptoms
OPTIME-CHF Milrinone 951 ↑AEs No
VERITAS Tezosentan 1.448 No No
EVEREST Tolvaptan 4.133 No Yes
LIDO Levosimendan 203 Yes No
vs. Dobutamine
Survive Levosimendan 1.327 No No
vs. Dobutamine
PROTECT Rolofylline 2.033 No No
VMAC Nesiritide 489 - Yes
ASCEND-HF Nesiritide 7.141 No No
Treatment of acute heart failure
Well almost an evidence free zone
JGF Cleland AHA 2010
ESC Guidelines 2012
McMurray et al. EHJ 2012; 33:1787–1847
Medikamentöse Therapie der dekomp. Herzinsuffizienz
- Schleifendiuretika -
Klinische Indikation - bei Hypervolämie und dekompensierter Herzinsuffizienz (IA) rasche
symptomatische Besserung durch venöse Vasodilatation, Diurese
durch Hemmung der Na+-K+2Cl- Pumpe im aszendieren Schenkel der
Henle-Schleife.
Probleme
- keine prospektiven kontrollierten Studien über den Einfluss einer
akuten und chronischen Therapie mit Diuretika auf Prognose.
- bei fortgeschrittener Herzinsuffizienz häufig Diuretikaresistenz.
- intravaskuläre Volumendepletion, neurohumorale Aktivierung.
- Nierenschädigung (struktur. Schädigung im distalen Tubulus).
- Dosierung und Applikation ungeklärt
Hochdosiert vs. niedrig dosiert
Bolus vs. kontinuierliche Infusion
Diuretic Strategies in Patients
with Acute Decompensated Heart Failure
Dose
308 patients with ADHF: treatment with i.v. furosemide
Bolus every 12 h Continuous infusion
High dose Low dose High dose Low dose
High dose: 2.5 times the previous oral dose
Low dose: Equivalent to the previous oral dose
*
*
Coprimary end points
- patients’ global assessment of symptoms, quantified as the area
under the curve of the score on a visual-analogue scale over the
course of 72 h
- change in the serum creatinine level from baseline to 72 hours
Felker et al. N Engl J Med 2011;364:797-805
Dose
Felker et al. N Engl J Med 2011;364:797-805
Kaplan–Meier Curves for the Clinical Composite End Point
of Death, Rehospitalization, or Emergency Department Visit
Dose
*
*
0
5
10
15
20
25
30
dose increase
at 48 h
switch to oral
diuretics at 48 h
high dose
low dose
% p
ati
en
ts
From Felker et al. N Engl J Med 2011;364:797-805
Dose
ESC Guidelines 2012
McMurray et al. EHJ 2012; 33:1787–1847
Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide
versus high-dose furosemide plus low-dose isosorbide dinitrate in severe
pulmonary oedema
Inclusion criteria
Patients with pulmonary edema (chest X-ray),
oxygen saturation < 90%
Group A
56 patients
110 patients randomized
Group B
54 patients
52 patients completed trial
Initial treatment
Oxygen 10 L/min, furosemide 40 mg i.v.,
morphine 3 mg i.v.
52 patients completed trial
3 mg ISDN i.v. every 5 min 80 mg bolus of furosemide i.v. every 15 min and
ISDN 1 mg/h, increased by 1 mg/h every 10 min
Treatment was continued in both groups until oxygen saturation increased to at least 96%
or mean arterial blood pressure decreased by at least 30% or to lower than 90 mm Hg
* *
* *
Cotter et al. Lancet 1998; 351: 389–93
High dose ISDN High dose Furosemide
+ low dose ISDN
Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide
versus high-dose furosemide plus low-dose isosorbide dinitrate in severe
pulmonary oedema
Cotter et al. Lancet 1998; 351: 389–93
SVR
Hypervolemia
Cardiac Lesion Depressed Ventricular
Performance
Neurohumoral Activation
Sympathetic Nervous System
RAAS
Endothelin
Vitious Circle in Acute Decompensated Heart Failure
Cardiac
Output
Therapeutic target
Decrease of SVR vitious circle
Therapeutic target
Decrease of preload
McMurray et al. EHJ 2012; 33:1787–1847
ESC Guidelines 2012
Loeb et al. Circulation 1977;55:375
Limitations of Inotropic Agents
- cAMP generating drugs: ↑ventricular arrhythmias
- Progression of LV dysfunction
↑ myocardial VO2 induced by ↑myocardial contractility and ↑ HR (catecholamies)
↑ cytoplasmic Ca++-overload
Untoward mechanism associated with loop diuretics (furosemide)
- Electrolyte abnormalities
- Neurohormonal activation
- Worsening of renal function
- Loss of efficacy in advanced heart failure
Treatment of ADHF
Definition
Symptome
Prognose
Aktuelle Studienlage
Neue Pharmaka
Behandlung der akuten Herzinsuffizienz
Myosinaktivatoren
Omecamtiv Mercabil
Neue natriuretische Peptide
Ularitide
sCG-Aktivatoren
Cinaciguat
Serelaxin
Teichmann et al. Curr Heart Fail Rep 2010; 7:75–82
Relaxin ist ein Peptidhormon, dessen Blutspiegel bei schwangeren
Frauen deutlich erhöht ist
Produktionsorte: Corpus luteum, Endometrium, Placenta, Mamma,
Prostata
Relaxin
Serelaxin, recombinant human relaxin-2,
for treatment of acute heart failure
Primary endpoints
Dyspnoea improvement
- Change from baseline in the visual analogue scale
area under the curve (VAS AUC) to day 5
- Proportion of patients with moderate or marked
dyspnoea improvement measured by Likert scale
during the first 24 h, both analysed by ITT
Inclusion criteria
- AHF (within the previous 16 h)
- dyspnoea at rest or with minimum exertion,
- pulmonary congestion on chest radiograph,
- BNP ≥ 350 ng/L or NT-proBNP ≥ 1400 ng/L
- mild to-moderate renal dysfunction
(GFR MDRD 30 -75 mL/min per 1.73 m )
- BPsyst. > 125 mm Hg
- 40 mg intravenous furosemide or equivalent
before screening
2
Teerlink et al. Lancet. 2013 5;381:29-39
Intervention
48-h intravenous infusions of
placebo or serelaxin (30 μg/kg per
day) within 16 h
RELAX-AHF
Teerlink et al. Lancet. 2013 5;381:29-39
RELAX-AHF Cardiovascular death
All cause death
Cardiovascular death or readmission
to hospital for heart failure or renal failure (%)
The signs and symptoms of congestion present
on study day 2
Teerlink et al. Lancet. 2013 5;381:29-39
Effect of Serelaxin on Cardiac, Renal, and Hepatic Biomarkers in the
Relaxin in Acute Heart Failure (RELAX-AHF) Development Program
Metra et al. J Am Coll Cardiol 2013;61:196–206
Risk for Death by Early Changes in Markers of Organ Function, Damage, and Congestion
Effect of Serelaxin on Cardiac, Renal, and Hepatic Biomarkers in the
Relaxin in Acute Heart Failure (RELAX-AHF) Development Program
Early Changes From Baseline in Laboratory Values
Metra et al. J Am Coll Cardiol 2013;61:196–206
RELAX-AHF-2
Primary objective
To demonstrate that serelaxin is superior to
placebo in reducing CV death in AHF patients
during a follow-up period of 180 days
Zusammenfassung
Akut dekompensierte (chronische) Herzinsuffizienz
• Dyspnoe das führende Symptom
• Schlechte Prognose: 1-Jahresmortalität > 25%
• Keine Evidenz-basierten Daten zur Prognose-
besserung durch eine Pharmakotherapie
Ziel: symptomatische Besserung ohne die Prognose
zu verschlechtern
• Nitrate, Diuretika: Besserung der Symptome
• Neue Therapieansätze
- Serelaxin
- …