Organ dysfunction in acute heart failure: Cardio-hepatic syndrome

Alexandre Mebazaa Department of Anesthesia & Critical Care University Hospitals Saint Louis – Lariboisière, Paris, France University Paris 7; INSERM – UMR 942 Conflict of interest

• Speaker’s bureau Alere, Edwards, Thermofischer

• Consultant for Bayer, Cardiorentis, Novartis, Orion, Vifor Pharma Online, free access

Short version: HFA/EUSEM/SAEM Eur Heart Journal 2015; Long version: Eur J Heart Failure 2015 ‘Clinical scenario 2’ in the CCU: dyspnoea + SBP 110-150 mmHg Decompensated chronic heart failure

• Dyspnoea develops gradually • Gradual increase in body weight • Systemic oedema • Minimal pulmonary oedema It is a systemic illness: • Possible renal dysfunction • Anaemia • Low albumin levels • Increased pulmonary congestion • Systemic congestion Acute heart failure = right & left ventricular failure: results of meta-analysis

LV failure

RAP - right atrial pressure PCWP - pulmonary capillary wedge pressure Ishihara S et al (submitted for publication) “Butterfly” pattern on chest X-ray

Monnier-Cholley L Chest X-ray in Acute Heart Failure in Mebazaa A et al (Eds) Acute Heart Failure (2009) Springer Science & Business Media Acute heart failure = right & left ventricular failure: results of meta-analysis

RV failure

RAP - right atrial pressure PCWP - pulmonary capillary wedge pressure Ishihara S et al (submitted for publication) Cardiorenal Syndrome Type I ? Acute setting ?

‘abrupt worsening of cardiac function (e.g. from ADHF) leading to acute kidney injury’ Ronco et al. JACC 2008, 52:1527-39 Ronco C et al. J Am Coll Card 2008, 52:1527-39 Effects of CVP, CI, SBP and PcwP on worsening renal function In Acute Heart Failure patients CVP (p<0.01) CI

SBP PCWP Worsening Renal Function (%)

Mullens et al. JACC 2009, 53:589-596 Association between baseline creatinine level and invasive haemodynamics in AHF: results of a meta-analysis

p=0.30 p=0.006

p=0.58

p=0.007

Ishihara S et al (submitted for publication) Gheorghiade et al. Eur J Heart F 2010 Abstract of the review

« The main reason for hospitalization for acute heart failure is CONGESTION, rather than low cardiac output ».

Gheorghiade et al. Eur J Heart F 2010 Several interactions have been described in acute heart failure

- Cardio-renal syndromes

- Cardio-liver syndrome(s) ??? EFICA Laboratory Tests on Admission

Zannad F, Mebazaa A, et al. Eur J Heart Fail. 2006 EFICA Risk Factors of 4-week Mortality

Zannad F, Mebazaa A, et al. Eur J Heart Fail. 2006 DANGER Mechanical ventilation can worsen liver congestion

• 38 y.o. man, dilated cardiomyopathy • referred to the emergency room for shortness of breath • predominant right heart failure • major hepatic cytolysis (AST: 10000 IU/l; ALT: 5000); lactate: 5.4 mmol/L; PT 35% • Renal failure Gatecel et al. Anesthesiology, 1995, 82:588 Mechanical ventilation can worsen liver congestion

Gatecel et al. Anesthesiology, 1995, 82:588 Mechanical ventilation can worsen liver congestion

Gatecel et al. Anesthesiology, 1995, 82:588 Arterial pressure

Normal Intra-tissular pressure = 0

Outflow pressure Effect of Heart

MAP > Tissular pressure Failure Stable on Organ CHF Congestion MAP < Tissular pressure

AHF ± high PAP volume loading

PA

RAP ARVF TR RV

Liver/Kidney CONGESTION

Liver dysfunction in AHF: Clinical characteristics Alk Phosphatase Transaminases

normal abnormal normal abnormal (22%) (37%)

Nikolaou et al Eur Heart Journal 2013 6-month mortality as a function of liver cytolysis

Nikolaou et al Eur Heart Journal 2013 6-month mortality as a function of cholestatis

Nikolaou et al Eur Heart Journal 2013 AHF-induced liver congestion (increased BNP)

Normal bile duct bile duct liver lobule compression compression (increased AP) (increased AP)

+ + + +++ +++ + +

and cytolysis (increased transaminanses) Nikolaou et al Eur Heart Journal 2013 AHF-induced liver congestion (increased BNP)

Normal bile duct bile duct liver lobule compression compression (increased AP) (increased AP)

+ + + +++ +++ + +

and cytolysis (increased transaminanses) Nikolaou et al Eur Heart Journal 2013 Factors associated with elevated alkaline phosphatase

Nikolaou et al Eur Heart Journal 2013

ALARM-HF: IV treatment at admission

inotropes

Mebazaa et al Intensive Care Medicine 2011 0.6 Epinephrine 0.5 Norepinephrine 0.4

0.3 Dopamine Dobutamine 0.2 In-hospital mortality Whole cohort

Diuretics 0.1 Levosimendan

0.0 Vasodilatators 0 5 10 15 20 25 30 Days Online, free access

HFA/EUSEM/SAEM Eur Heart Journal 2015 What to do in the first 30-60 min (1)

HFA/EUSEM/SAEM Eur Heart Journal 2015 What to do in the first 30-60 min (1)

SEVERITY SCORE

HFA/EUSEM/SAEM Eur Heart Journal 2015 Next 120 min

HFA/EUSEM/SAEM Eur Heart Journal 2015 Admission/ discharge

HFA/EUSEM/SAEM Eur Heart Journal 2015 Main messages (1)

•Congestion is the main disease in acute heart failure

•Novel therapies, such as novel vasodilators, aim at reducing congestion

•« time is muscle « Main messages (2)

•There are evidence for a cardio-liver syndrome in AHF

•Cholestasis is associated with signs of congestion

•Hepatolysis is associated with decreased blood flow In summary

• There are evidence for a cardio-liver syndrome in AHF

• Cholestasis is associated with signs of congestion

• Hepatolysis is associated with decreased blood flow