The Heart in Concert: Do Other Organs Matter? The Liver

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The Heart in Concert: Do Other Organs Matter? The Liver Pascal de Groote CHRU Lille France

DECLARATION OF CONFLICT OF INTEREST I have no conflict of interest with this presentation

Impact of liver disease on cardiac function Cirrhotic Cardiomyopathy Impact of congestive heart failure on liver function Ischemic hepatitis Congestive liver

The Heart of the Cirrhotic Patient

Cirrhotic Cardiomyopathy: Definition Chronic cardiac dysfunction in patients with cirrhosis, in absence of known cardiac disease, irrespective of the etiology of cirrhosis Exclusion of alcoholic cardiomyopathy and of some specific etiologies inducing liver and cardiac diseases, such as hemochromatosis

Hyperkinetic state related in part to the increase of arterial compliance with volume expansion: high cardiac output state that could induce heart failure Often, clinically silent Cirrhotic Cardiomyopathy Normal echocardiography at rest: moderate LV hypertrophy and moderate diastolic abnormalities Blunted response to exercise or during stress (infection) Possible LV outflow tract obstruction Other cardiac abnormalities QT interval prolongation Zardi: J Am Coll Cardiol 2010;56:539 Raval: J Am Coll Cardiol 2011;58:223 Mandell: Trends Anaest Crit Care 2011

Cirrhotic Cardiomyopathy Normalization of echocardiographic abnormalities and of the stress response after liver transplantation Stress Response 70 60 50 40 30 20 10 0-10 63 46 65 6-2 D HR D LVEF 7 Controls Cirrhotic patients After Transplantation Torregrosa: J Hepatology 2005;42:68

Stent Implantation Major problem is a possible severe heart decompensation during a specific treatment of cirrhosis During stent implantation, increase venous return could induce heart decompensation 120 100 80 60 40 20 0 % of increase 111% 92% 16% PAP P Wedge CO Huonker: Gut 1999;44:743

Liver Transplantation: Acute Effects Retrospective study in 209 patients with liver transplantation Hemodynamic definition of an abnormal cardiac response during reperfusion 47 patients had an abnormal cardiac response (22%) No echocardiographic difference Hyponatremia and low CVP were independent predictors of abnormal cardiac response No impact on mortality Ripoll: Transplantation 2008;85:1766

Liver Transplantation: Sub Acute Effects Retrospective study in 34 patients Acute pulmonary edema in 47% of the patients (radiological diagnosis) (n = 16 patients) 6 patients < 24 hours after surgery and 10 patients > 24 hours Related in part to post-operative excess fluid replacement Snowden: Liver Transpl 2000;6:466

Liver Transplantation: Chronic Effects LV systolic dysfunction after liver transplantation: 7% (6 of 86 patients) Selection of patient at risk Very difficult to diagnose for an individual patient Increase mean pulmonary pressure: 19.6±6.8 vs 25.4±7.8 mmhg Improvement several months after liver transplantation Eimer: Am J Cardiol 2008;101:242

Cirrhotic Cardiomyopathy: Take Home Messages Often clinically silent: not necessary to search Reversible after liver transplantation Risk of heart failure decompensation After stent implantation (TIPS) After liver transplantation During acute stress (infection) High risk cirrhotic patient: patients with normal or moderately depressed LVEF In cirrhotic patients with LV systolic dysfunction, the standard CHF treatment must be started

The Liver of the Heart Failure Patient Ischemic Hepatitis Congestive Liver

Rare condition: < 1% Ischemic Hepatitis Biological diagnosis in CHF patients Acute increase in serum aminotransferase: > 10 times the upper limit of normal and a decrease in pro-thrombin time Physiopathology: Related to a sudden and profound hepatic hypoxia related to a reduction either in blood pressure or in hepatic blood flow and/or related to a severe arterial hypoxemia Hepatic congestion plays a significant role Histological feature: centrilobular necrosis Naschitz: Am Heart J 200;140:111

Ischemic Hepatitis Dramatic acute but transient increase in serum aminotransferase

Mechanisms of Ischemic Hepatitis Henrion: Medicine 2003; 82: 392

Ischemic Hepatitis Profound hypotension alone is not sufficient to induce ischemic hepatitis Control group: trauma with shock Seeto: Am J Med 2000; 109: 109

Congestive Liver Frequent in patients with chronic CHF Increased central venous pressure Histological feature: from congestion to fibrosis or cirrhosis Often clinically silent or Presence of ascites with high protein content (> 25 g/l) Increase in bilirubin and in alkaline phosphatase Naschitz: Am Heart J 200;140:111

Myers: Hepatology 2003; 37: 393 Abnormal liver function tests in CHF patients 83 patients with cardiac hepatopathy

Histological features Myers: Hepatology 2003; 37: 393

Prevalence of abnormal liver function tests 2679 North American patients from the 3 arms of the CHARM program Prevalence of abnormal liver function tests: 323 chronic severe patients admitted for right heart catheterization Decrease albumin: 18.3% Increase total bilirubin: 13% LV systolic dysfunction: 15.8% LV preserved EF: 9.4% 62% Inscrease alkaline phosphatase: 14% 43% Increase SGOT: 4.1% Increase SGPT: 3.1% 18% Allen: Eur J Heart Fail 2009; 11: 170 Van Deursen: J Card Fail 2010; 16: 84

Impact on Prognosis Liver diseases increase mortality in CHF patients 2624 patients with incident acute heart failure Mortality rates: At 30 days: 10.7% At 1 year: 32.9% Lee: JAMA 2003; 290: 2581

Liver function tests: Acute heart failure OBSERVE registry Liver function tests were not included ADHERE score HFSS score Seattle HF score 0 Connaor: Am Heart J 2008; 156: 662

Allen: Eur J Heart Fail 2009; 11: 170 Liver function tests: CHARM Program 2679 North American patients from the 3 arms of the CHARM program Cardiovascular death and HF hospitalizations

Allen: Eur J Heart Fail 2009; 11: 170 Liver function tests: CHARM Program Multivariable model: Cardiovascular death and HF hospitalizations Cardiovascular death > 8 mg/l

Liver Function Tests: Chronic severe CHF Patients 323 chronic severe patients admitted for right heart catheterization Mean age: 53±15 years, LVEF: 28±13% During a median follow-up period of 7.9 [4.1-11.8] years, there were 122 deaths Van Deursen: J Card Fail 2010; 16: 84

RV Failure Score Retrospective analysis in 197 patients with LVAD RV Failure: Mortality rate: 10% vs 38% OR: 5.5 [2.6-11.8] RV Failure Score 4 points: Need for vasopressor agents 3 points: Creatinine 23 mg/l 2.5 points: Bilirubin 20 mg/l 2 points: AST 80 UI/l Matthews: J Am Coll Cardiol 2008; 51:2163

Hepatic Function after LVAD Russel: Circulation 2009; 120: 2352

Conclusions Liver function tests are often abnormal in patients with congestive heart failure Ischemic hepatitis = acute heart failure Congestive liver = chronic heart failure The presence of abnormal liver function tests is an independent predictor of survival in CHF patients