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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

- …