Echokardiographie Update 2013 München 14.- 15. Dezember 2013
Notfall-/Intensivmedizin: akute Herzinsuffizienz Therapie der akuten Herzinsuffizienz S. Felix Klinik für Innere Medizin B Ernst-Moritz-Arndt-Universität Greifswald
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Behandlung der akuten Herzinsuffizienz
Definition Symptome Prognose Aktuelle Studienlage Neue Pharmaka
Acute Heart Failure 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
Worsening HF De novo HF
Decompensated HF Pulmonary oedema Cardiogenic shock
End-stage HF Hypertensive HF Right HF Gheorghiade et al. J Am Coll Cardiol 2013;61:391–403
ESC Guidelines Eur Heart J 2008; 29: 2388–2442
Behandlung der akuten Herzinsuffizienz
Definition
Symptome Prognostische Faktoren Aktuelle Studienlage Neue Pharmaka
Abnormal LV function → sytemic congestion
Gheorghiade et al. Eur J Heart Failure 2010; 12: 423–433
AHF- Symptoms Adhere
%
100 90 80 70
DD ADHF vs pulmon. disease
60 50 40
-
30
-
ECG Chest x-ray NT-pro BNP ≥ 300 pg/mL BNP ≥ 100 pg/ml ECHO
20
ESC Guidelines 2012
10 0 Dyspnea
From Adams et al. Am Heart J 2005;149:209-16
Rales Peripheral Edema
Abnormal LV function
→
systemic congestion
Gheorghiade et al. EurJ Heart Failure 2010; 12: 423–433
The impact of early standard therapy on dyspnoea in patients with AHF URGENT-dyspnoea study
Mebazaa et al. Eur Heart J 2010; 31: 832–841
Behandlung der akuten Herzinsuffizienz
Definition
Symptome Prognose Aktuelle Studienlage
Neue Pharmaka
EuroHeart Failure Survey II (2.981 AHF patients)
Harjola et al. Eur J Heart Failure 2010;12: 239–248
Behandlung der akuten Herzinsuffizienz
Definition Symptome Prognose Aktuelle Studienlage Neue Pharmaka
Clinical Trials in worsening HF/ADHF
Trial
Agent
Pts
Effects on Outcome
Effects on Symptoms
↑AEs
No
1.448
No
No
4.133
No
Yes
Yes
No
1.327
No
No
2.033
No
No
-
Yes
No
No
OPTIME-CHF
Milrinone
951
VERITAS
Tezosentan
EVEREST
Tolvaptan
LIDO
Levosimendan vs. Dobutamine
203
Survive
Levosimendan vs. Dobutamine
PROTECT
Rolofylline
VMAC
Nesiritide
489
ASCEND-HF
Nesiritide
7.141
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
Dose
Diuretic Strategies in Patients with Acute Decompensated Heart Failure 308 patients with ADHF: treatment with i.v. furosemide
Bolus every 12 h
*
High dose
Low dose
Continuous infusion
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
Dose
Felker et al. N Engl J Med 2011;364:797-805
Dose Kaplan–Meier Curves for the Clinical Composite End Point of Death, Rehospitalization, or Emergency Department Visit
Felker et al. N Engl J Med 2011;364:797-805
Dose
30 % patients
25
*
20
*
15
high dose low dose
10 5 0 dose increase at 48 h
switch to oral diuretics at 48 h
From Felker et al. N Engl J Med 2011;364:797-805
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%
Initial treatment Oxygen 10 L/min, furosemide 40 mg i.v., morphine 3 mg i.v.
110 patients randomized
Group A * 56 patients
Group B * 54 patients
* 3 mg ISDN i.v. every 5 min
* 80 mg bolus of furosemide i.v. every 15 min and
52 patients completed trial
52 patients completed trial
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
Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema
High dose ISDN
High dose Furosemide + low dose ISDN
Cotter et al. Lancet 1998; 351: 389–93
Vitious Circle in Acute Decompensated Heart Failure
Cardiac Lesion Depressed Ventricular Performance
SVR Hypervolemia
Cardiac Output
Therapeutic target Decrease of preload
Neurohumoral Activation Sympathetic Nervous System RAAS Endothelin Therapeutic target Decrease of SVR vitious circle
ESC Guidelines 2012
McMurray et al. EHJ 2012; 33:1787–1847
Loeb et al. Circulation 1977;55:375
Treatment of ADHF 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
Behandlung der akuten Herzinsuffizienz
Definition Symptome
Prognose Aktuelle Studienlage Neue Pharmaka
Myosinaktivatoren Omecamtiv Mercabil
sCG-Aktivatoren Cinaciguat Serelaxin Neue natriuretische Peptide Ularitide
Relaxin Relaxin ist ein Peptidhormon, dessen Blutspiegel bei schwangeren Frauen deutlich erhöht ist Produktionsorte: Corpus luteum, Endometrium, Placenta, Mamma, Prostata
Teichmann et al. Curr Heart Fail Rep 2010; 7:75–82
Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure 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 m2) BPsyst. > 125 mm Hg 40 mg intravenous furosemide or equivalent before screening
Intervention 48-h intravenous infusions of placebo or serelaxin (30 μg/kg per day) within 16 h
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 Teerlink et al. Lancet. 2013 5;381:29-39
RELAX-AHF
Teerlink et al. Lancet. 2013 5;381:29-39
RELAX-AHF
Cardiovascular death
Cardiovascular death or readmission to hospital for heart failure or renal failure (%)
All cause death
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 Risk for Death by Early Changes in Markers of Organ Function, Damage, and Congestion
Metra et al. J Am Coll Cardiol 2013;61:196–206
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
Akut dekompensierte (chronische) Herzinsuffizienz Zusammenfassung •
Dyspnoe das führende Symptom
•
Schlechte Prognose: 1-Jahresmortalität > 25%
•
Keine Evidenz-basierten Daten zur Prognosebesserung durch eine Pharmakotherapie Ziel: symptomatische Besserung ohne die Prognose zu verschlechtern
•
Nitrate, Diuretika: Besserung der Symptome
•
Neue Therapieansätze - Serelaxin -…
