liver dysfunction

Liver dysfunction in AHF syndromes: clinical and prognostic

implications

J. ParissisHeart Failure Clinic

Attikon University Hospital,Athens, Greece

Disclosures:

Research grants from Abbott USA and Orion Pharma Finland as

ALARM investigator, and Novartis international.

• Ten liver function tests were evaluated in a study of 135 cases of chronic protracted congestive heart failure of which 54 came to autopsy.

• Seventy-four per cent of the patients had at least one abnormal determination although only 30 per cent of the tests performed were out of the normal range.

• There is definite impairment of liver function in congestive heart failure. The exact basis for this change remains unknown.

Circulation. 1950;2:286-297

The Splanchnic Vasculature: Capacitance Function and Cardiac Pre-load

Verbrugge et al. J Am Coll Cardiol 2013;62:485–95

Hepatorenal Reflex

Verbrugge et al. JACC 2013

Pathophysiology in HFCan ischemic hepatitis be attributed only to hypotension?

Samski et al. JACC 2013

Transaminases in Ischemic Hepatitis

Sharp rise and fallALT/LDH<1.5

Cardio Hepatic Interactions•FORWARD HF/CARDIOGENIC SHOCK HYPOXIC HEPATITIS

• BACKWARD HF/CHRONIC CONGESTIONCIRRHOTIC LIVER

• LIVER CIRRHOSIS CIRRHOTIC CARDIOMYOPATHY

Distribution of abnormal liver enzymes in HF

Auer J. Eur Heart J 2013;34:711–714

CHF: prevalence & clinical significance of liver dysfunction

Association with• NYHA• JV distention, edema• EF• RVSP• TR

1214 13

0Bilirubin γGT ALP ALT/AST Αlbumin

Poelzl (2014)

CHARM (2009)

Allen et al. Eur J HF 2009Poelzl et al. Eur J Clin Invest 2012

GGT, T-Bil, GGT, T-Bil, and ALPALP are related to disease severity

p <0.0001 p <0.0001p <0.0001

Poelzl G, et al. EJCI, 2012, 42:153

AST, AST, and ALTALT are not related to disease severity

p=0.168 p=0.495

Poelzl G, et al. EJCI, 2012, 42:153

CHF: prevalence & clinical significance of liver dysfunction

Allen et al. Eur J HF 2009

Prevalence and Prognostic Significance of Elevated g-Glutamyltransferase in Chronic HF

Poelzl et al. Circ Heart Fail. 2009;2:294-302

Prevalence of elevated GGT was 42.9% in men (GGT >65 U/L) and 50.2% in women(GGT> 38 U/L) with CHF.

Synergistic effect of hepatic and renal dysfunction on outcomes in CHF patients

Poelzl et al. Eur J Inter Med 2013;24:177–182

MELD score=11.2x(ln INR)+0.378x(ln bil)+0.957x(ln creat)+0.643

MELD-XI score=5.11x(ln bil)+11.76x(ln creat)+9.44

Cardiohepatic syndrome in CHF: general concepts

TheThe cardio-hepatic syndrome cardio-hepatic syndrome in chronic in chronic heart failure is :heart failure is :

- frequentfrequent

- characterized by a predominantly predominantly cholestatic cholestatic enzyme pattern

-- associated with disease severity associated with disease severity

- related to prognosisrelated to prognosis

AHF: prevalence & clinical significance of LFTs

0Bilirubin γGT ALP ALT/AST Αlbumin

SURVIVE

ESCAPE

EVEREST

Abnormal LFTs:

Nikolaou et al. Eur Heart J 2013Ambrosy et al. Eur J Heart Fail 2012Scholfild et al. J Cardiac Fail 2014

Prevalence of elevated ALT and aspartate AST at admission by ejection fraction and clinical profile at presentation

European Heart Journal: Acute Cardiovascular Care 2013 2: 99

Additive values of abnormal transaminases and abnormal alkaline phosphatase on a short- andlong-term outcome

Nikolaou M, Parissis J, …, Mebazaa A. EHJ 2013;34:742-749

Assessment of Acute Heart Failure Syndromes: the role of hepatic dysfunction

Modified from Nohria et al. Am J Cardiol 2005;96[suppl]:32G–40G

High Transaminases plus ALP

High Transaminases

High ALP Normal

GGT levels in ADHF: prognostic value and relationship with renal function

Serum creatinine

Parissis et al. Int J Cardiol 2014

eGFReGFR and GGTGGT are related to CVPCVP

p = 0.007 p = 0.001

Poelzl G, courtesy

eGFR GGT

Standardized regression

coefficient beta

P-value Standardized regression

coefficient beta

P-value

Male gender 0.207 0.011 0.182 0.023

Age 65a -0.096 0.224 -0.022 0.776

Ischemic aetiology -0.160 0.054 0.192 0.020

Diabetes -0.049 0.550 0.210 0.117

Hypertension -0.211 0.008 -0.87 0.261

Alcohol consumption -0.041 0.601 -0.087 0.266

LV-EF 35% -0.164 0.047 0.006 0.945

NYHA III/IV -0.065 0.459 0.118 0.178

CVP -0.225 0.008 0.337 <0.001

CI 0.060 0.470 0.017 0.835

Determinants of worsening renal and hepatic function (n = 205)

Poelzl G, courtesy

Levosimendan, compared to dobutamine, reduces enzymatic markers associated with liver congestion: A SURVIVE subanalysis

Day 1 Day 3 Day 5Day 1 Day 3 Day 5

AST APALT

*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.

80 75 111Baseline, μ, IU/L

0.008 0.002 <0.001P-value*