Cardiac cirrhosis (congestive hepatopathy) includes a spectrum of hepatic derangements that occur in the setting of right-sided heart failure. Clinically, the signs and symptoms of congestive heart failure (CHF) dominate the disorder. Unlike cirrhosis caused by chronic alcohol use or viral hepatitis, the effect of cardiac cirrhosis on overall prognosis has not been clearly established. As a result, treatment is aimed at managing the underlying heart failure.[1, 2]
Distinguishing cardiac cirrhosis from ischemic hepatitis is important. The latter condition may involve massive hepatocellular necrosis caused by sudden cardiogenic shock or other hemodynamic collapse. Typically, sudden and dramatic serum hepatic transaminase elevations lead to its discovery. Although cardiac cirrhosis and ischemic hepatitis arise from distinct underlying cardiac lesions (right-sided heart failure in the former and left-sided failure in the latter), in clinical practice they may present together.
Despite its name, cardiac cirrhosis (which usually implies congestive hepatopathy that results in liver fibrosis) rarely satisfies strict pathologic criteria for cirrhosis. The terms congestive hepatopathy and chronic passive liver congestion are more accurate, but the name cardiac cirrhosis has become convention. For the remainder of this chapter, the term cardiac cirrhosis will be used to mean congestive hepatopathy with or without liver fibrosis.
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Cardiac cirrhosis. Congestive hepatopathy with large renal vein.
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Cardiac cirrhosis. Congestive hepatopathy with large inferior vena cava.
Decompensated right ventricular or biventricular heart failure causes transmission of elevated right atrial pressure to the liver via the inferior vena cava and hepatic veins. At a cellular level, venous congestion impedes efficient drainage of sinusoidal blood flow into terminal hepatic venules. Sinusoidal stasis results in accumulation of deoxygenated blood, parenchymal atrophy, necrosis, collagen deposition, and, ultimately, fibrosis.
A separate theory proposes that cardiac cirrhosis is not simply a response to chronically increased pressure and sinusoidal stasis. Because intrahepatic vascular lesions are confined to areas of the liver with higher fibrotic burden, cardiac cirrhosis may require a higher grade of vascular obstruction, such as intrahepatic thrombosis, for its development. Thus, thrombosis of sinusoids and terminal hepatic venules propagates to medium-sized hepatic veins and to portal vein branches, resulting in parenchymal extinction and fibrosis.
Cardiac cirrhosis rarely occurs in the United States. Its true prevalence is difficult to estimate, since the disease typically remains subclinical and undiagnosed. The incidence of cardiac cirrhosis at autopsy has decreased significantly over the past several decades. This may be due to lower rates of uncorrected rheumatic heart disease and constrictive pericardial disease.
Mortality/Morbidity
The effect of cardiac cirrhosis on mortality and morbidity rates is unknown. The severity of the patient's underlying cardiac disease, which is typically advanced and chronic, is the major determinant of overall outcome.
Sex
Comparative sex data for cardiac cirrhosis do not exist. However, because CHF is more common in men than women in the United States, the same is likely for cardiac cirrhosis.[3]
Age
No published data exist. However, the prevalence of cardiac cirrhosis in the United States, like that of CHF, almost certainly increases with age.
Symptoms of CHF almost always mask gastrointestinal symptoms. Symptoms typically progress insidiously but may present suddenly and dramatically in cases of constrictive pericarditis or acute right ventricular decompensation. Patients may present with asymptomatic liver enzyme abnormalities, jaundice, and right upper quadrant discomfort. Case reports of fulminant hepatic failure have also been reported.
In addition to CHF, a patient's past medical history is likely to include one or more of the following:
Coronary artery disease
Myocardial infarction
Hypertension
Dilated cardiomyopathy
Valvular heart disease
Chronic alcohol abuse
Chronic obstructive pulmonary disease (COPD)
Cor pulmonale
Pulmonary hypertension
Constrictive pericarditis
Rheumatic heart disease
Symptoms may be divided into those that accompany right ventricular heart failure and the additional findings of biventricular failure.
Symptoms associated with isolated right-sided heart failure are as follows:
Dependent edema and weight gain
Increased abdominal girth
Right upper quadrant abdominal pain
Nocturia
Progressive fatigue
Anorexia, nausea, and vomiting
Symptoms associated with biventricular heart failure are as follows:
Progressive dyspnea
Orthopnea
Paroxysmal nocturnal dyspnea
Wheezing and/or cough (ie, cardiac asthma)
Anxiety: Multifactorial causes include dyspnea, palpitations, and increased sympathetic tone.
Signs of heart failure dominate the physical examination findings.
Edema
Edema typically occurs in the lower extremities and dependent regions, which may progress to anasarca in cases of advanced and untreated heart failure. Chronic edema may be associated with lower extremity pigmentation, induration, and cellulitis.
Jugular venous pressure
Jugular venous pressure is elevated. Further distention of neck veins may be elicited with application of pressure over the right upper quadrant for as long as 1 minute (ie, hepatojugular reflux).
Paradoxical rise in jugular venous pressure during inspiration (ie, Kussmaul sign) may indicate constrictive pericarditis, right ventricular heart failure, tricuspid stenosis, or cor pulmonale.
Right atrial pressure recordings reveal large a waves, indicating elevated right atrial pressure that may appear as presystolic liver pulsations.
Prominent v waves with rapid y descent indicate tricuspid regurgitation. Progression to a systolic, or c-v, wave occurs in severe tricuspid insufficiency and may appear as systolic liver pulsations.[4]
Rales
Rales on lung examination indicate biventricular CHF. Decreased basilar breath sounds from pleural effusion also are common.
Cardiac abnormalities
Cardiac examination may reveal abnormalities related to right ventricular failure, tricuspid regurgitation, or both.
Abnormal systolic sternal or left parasternal lift signifies both pulmonary and right ventricular hypertension.
Right ventricular third and fourth heart sounds commonly are appreciated at the lower left sternal border of the sternum or over the xiphoid. Right ventricular S 3 suggests right ventricular failure. Right ventricular S 4 results from right atrial contraction into a noncompliant right ventricle. Inspiration increases the intensity of both extra heart sounds.
The holosystolic, high-pitched, blowing murmur of tricuspid insufficiency often accompanies severe right ventricular dilation and failure. The murmur is best heard at the lower left sternal border. But in cases of severe right ventricular enlargement, the murmur may be displaced as far laterally as the left midclavicular line. The murmur intensifies with inspiration and decreases with expiration.
Signs of pulmonary hypertension include a closely split S 2 with a loud pulmonic component. The Graham Steell murmur of pulmonary hypertensive pulmonic regurgitation is a high-pitched, blowing diastolic murmur beginning with a loud P2 and continuing through most of diastole.
Hepatomegaly
Hepatomegaly is common, usually presenting as a firm, hard liver.
Elevated hydrostatic pressure within the hepatic veins and the peritoneal venous drainage system causes cardiac ascites. Protein-losing enteropathy with subsequent reduction of plasma oncotic pressure also may exacerbate ascites.
Causes of cardiac cirrhosis mirror the many etiologies of right-sided CHF, including congenital heart disease. Although inferior vena caval thrombosis and Budd-Chiari syndrome exhibit similar pathophysiology, they are categorized separately and are not included as causes of cardiac cirrhosis.
The most frequent causes of cardiac cirrhosis are the following:
Ischemic heart disease (31%)
Cardiomyopathy (23%)
Valvular heart disease (23%)
Primary lung disease (15%)
Pericardial disease (8%)
A study by Yoo et al suggested that the Fontan procedure is a significant risk factor for cardiac cirrhosis. The study included 46 patients with Fontan circulation, as well as 26 patients with right-sided heart failure and hepatic congestion. The Fontan patients were found, via transient elastography, to have a significantly higher liver-stiffness value than did the patients with right-sided heart failure. Moreover, a significant association was seen between liver stiffness in the Fontan patients and total bilirubin and albumin levels, white blood cell counts, and aspartate aminotransferase-to-platelet ratio indexes. The investigators found the age at which the Fontan procedure was completed and the total bilirubin level to be independent risk factors for hepatopathy.[5]
Evaluate severity of hepatic failure with liver function tests (LFTs), including hepatic transaminases, alkaline phosphatase, total bilirubin, and albumin.
The most common liver enzyme abnormality is an elevation of serum bilirubin. Patients with cardiac cirrhosis may exhibit modest elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and total bilirubin, as well as mild decreases in albumin.
Abnormal values are more common in patients with mean right atrial pressures in excess of 10 mm Hg and cardiac indices less than 1.5 L/min/m2.
Abnormalities typically remain clinically silent and resolve with compensation of heart failure.
Extreme elevations of AST and ALT should alert the clinician to other causes of liver failure, including ischemic, toxic, and viral hepatitis.
Prothrombin time
A study from the 1960s showed prothrombin time (PT) to be abnormal in as many as 80% of patients with acute or chronic right-sided heart failure.
Other laboratory studies
Evaluate serial cardiac enzymes, CBC count, urinalysis, and routine serum electrolytes in a patient with cardiac cirrhosis in the setting of new-onset heart failure.
Search for evidence of reversible causes of CHF. For example, obtain levels of serum iron, total iron-binding capacity, and ferritin in an evaluation for hemochromatosis when cardiac cirrhosis presents with significant or persistent LFT abnormalities. Thyroid-stimulating hormone (TSH) levels are indicated in patients with unexplained cardiac cirrhosis and atrial fibrillation.
Radiographic images may show cardiomegaly, pulmonary venous hypertension, interstitial or pulmonary edema, or pleural effusion. Pleural effusions typically are larger on the right.
An echocardiogram may diagnose the underlying cause of cardiac cirrhosis. Evaluation of biventricular size, mass, function, wall motion, and valves are indicated.
Because restrictive cardiomyopathy and pericardial constriction can lead to cardiac cirrhosis, specific attention should be paid to diastolic function parameters such as mitral inflow, pulmonary vein flow, mitral annular flow, and their responses to respiration.
Lack of inferior vena cava (IVC) respiratory variation (normally greater than or equal to 50% narrowing during inspiration) or IVC diameter greater than or equal to 2.3 cm suggest right-sided cardiac disease with increased right atrial filling pressures.
Subcostal Doppler view of hepatic veins demonstrating systolic flow reversal is highly specific for clinically significant tricuspid regurgitation.
Radionuclide imaging with thallium or technetium is a noninvasive means to identify reversible cardiac ischemia in patients with cardiac cirrhosis in the setting of new or decompensated heart failure. Technetium-labeled agents and positron-emission tomography (PET) identify dilated cardiomyopathy and determine myocardial function.
Consider abdominal Doppler US in the setting of ascites, right upper quadrant abdominal pain, jaundice, and/or abnormal serum LFTs that are refractory to effective treatment of underlying heart failure. The test is performed to search for an alternative diagnosis, such as Budd-Chiari syndrome.
Computed Tomography Scanning and Magnetic Resonance Imaging
CT scan and MRI help to diagnose restrictive and constrictive pericardial disease. These studies also may identify enlarged chamber size, ventricular hypertrophy, diffuse cardiomyopathy, valvular disease, and other structural abnormalities such as arrhythmogenic dysplasia of the right ventricle. Both can measure ejection fraction and effectively rule out cardiac cirrhosis. Body imaging may reveal evidence of cardiac cirrhosis, including hepatomegaly, hepatic congestion, IVC enlargement, and splenomegaly (see following images).
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Cardiac cirrhosis. Congestive hepatopathy with large renal vein.
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Cardiac cirrhosis. Congestive hepatopathy with large inferior vena cava.
Diagnostic paracentesis may distinguish between cardiac and other etiologies of ascites. The information is useful especially in patients with chronic alcoholism and uncharacterized cardiac disease. Evaluate fluid for cell count and differential, albumin, total protein, and cytology.
Typically, cardiac ascites will reveal a high serum-ascites albumin gradient (SAAG) greater than 1.1 g/dL and a high ascitic fluid total protein greater than 2.5 g/dL. Patients with cirrhotic ascites also have a high SAAG value, but ascitic fluid total protein will be greater than 2.5 g/dL only 10% of the time.[6] See the Ascites Albumin Gradient calculator.
Employ therapeutic paracentesis for ascites refractory to diuretic treatment. Because hepatic albumin synthetic function usually is preserved in cardiac cirrhosis, parenteral albumin supplementation after paracentesis is not indicated.
The procedure may be indicated in patients with cardiac cirrhosis and heart failure in the context of known or suspected coronary artery disease. The study is employed primarily to evaluate coronary arterial anatomy and the need for revascularization.
Perform right heart catheterization to diagnose pulmonary hypertension in the setting of suggestive physical examination or echocardiographic findings.
In less than 1% of patients with chronic liver failure, pulmonary hypertension occurs in the absence of underlying pulmonary or cardiac disease. This entity, known as portopulmonary hypertension, may progress to right ventricular failure and present a diagnostic challenge to determine whether liver failure or heart disease is the primary lesion.
The procedure is not indicated routinely. Needle biopsy is indicated in heart transplant candidates with ascites to rule out cirrhosis.
Endomyocardial biopsy
The procedure may be indicated in patients with cardiac cirrhosis with deteriorating clinical condition and a strong clinical suspicion for myocarditis. It also may be indicated in the presence of a systemic disease with possible cardiac involvement, such as hemochromatosis or sarcoid.
Cardiac cirrhosis is associated with characteristic histologic changes. The presence of centrilobular parenchymal atrophy, sinusoidal and terminal hepatic venular distention, and perisinusoidal collagen deposition establishes chronic passive hepatic congestion (CPC).
In more severe cases, centrilobular fibrosis develops and eventually may include diffuse fibrous septa[7] and regenerative nodules characteristic of true cirrhosis.
Histologic findings are bland, with an absence of inflammatory cells.
Exposure of the liver to venous hypertension alone has not been demonstrated to cause centrilobular necrosis (CLN); in practice, however, histologic features of both CPC and CLN frequently occur together. CPC and CLN form a morphological continuum reflecting degrees of preexisting hepatic congestion and acute liver hypoperfusion. The synergistic combination of CPC and CLN is known as centrilobular hemorrhagic necrosis, referred to more commonly as nutmeg liver.[8]
The liver's mottled gross appearance results from the contrast of red-brown centrilobular regions suffused with blood against viable, if somewhat fatty, periportal tissue.
No prospective studies have been performed to evaluate the medical treatment of cardiac cirrhosis. Because no data suggest that the presence of cardiac cirrhosis worsens mortality or morbidity rates, direct treatment at the underlying source of elevated right-sided heart pressure and hepatic venous congestion.
Note the following:
Initiate treatment in an inpatient setting, both to rule out ischemic heart disease and to administer IV diuretics.
In most cases, diuresis is the cornerstone of initial medical therapy for symptomatic relief.
Once the patient is euvolemic, beta-blockers and ace inhibitors should be added if the underlying cause is left ventricular dysfunction.
Spironolactone should be considered, especially if there is New York Heart Association class III or IV heart failure.
Consult with specialists in cardiology, gastroenterology, and diet and/or nutrition.
Definitive treatment of cardiac cirrhosis sometimes requires surgical intervention, particularly when the underlying structural or anatomic lesion remains symptomatic despite maximal medical therapy.
Examples of surgical intervention include the following:
Coronary artery bypass surgery or percutaneous transluminal coronary angioplasty for ischemic cardiomyopathy
Tricuspid valve repair or replacement for tricuspid regurgitation or tricuspid stenosis
Pericardiectomy (cardiac decortication) for constrictive pericarditis
Peritoneovenous shunt not indicated to treat cardiac ascites
Transjugular intrahepatic portosystemic shunt (TIPSS): This is generally contraindicated because of the risk of acute right-sided decompensation from increased venous return. One recent case report illustrated the use of TIPSS procedure in a patient with cardiac cirrhosis after heart transplant that resulted in a successful outcome.[9]
Cardiac transplantation can be considered for end-stage cardiomyopathy. The presence of cardiac cirrhosis with significant liver fibrosis is considered a contraindication to transplantation. Although standard transplant criteria applies, several caveats should be considered. First, right-heart failure can be accompanied by significant pulmonary hypertension, which may necessitate combined heart-lung transplant. Second, synthetic liver function may be affected, leading to bleeding complications associated with transplantation. However, a study examining the reversibility of cardiac cirrhosis in patients undergoing heart transplant showed that synthetic function significantly improved within 3 months after transplant.[10]
With few exceptions (eg, acute right ventricular myocardial infarction), diuresis is the cornerstone of initial management of cardiac cirrhosis. As cardiac cirrhosis is a direct complication of elevated central venous pressures, effective diuresis should improve hepatic derangements. Lack of improvement should prompt a search for primary hepatic disease.
Beyond diuretics, medical therapy should be directed at treating underlying heart failure and correcting the source of elevated right-sided heart pressures.
Clinical Context:
Increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.
Initial administration should be IV to avoid poor bowel absorption through edematous bowel mucosa. Start dosing low and increase to achieve desired diuresis and clinical effect. Useful clinical target is return to patient's baseline weight.
Rising serum BUN and creatinine levels are indicators of prerenal azotemia and suggest maximal diuresis has been achieved. Once determined, administer effective dose qd or bid.
Clinical Context:
For management of edema resulting from excessive aldosterone levels secondary to hepatic cirrhosis or CHF. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.
Initial treatment of cardiac cirrhosis usually requires a loop diuretic (eg, furosemide). Spironolactone may provide additional diuresis through its aldosterone antagonism effects.
Instruct patients to maintain a diary of their daily weights. Specific instructions may be issued to increase the patient's oral diuretic dose, as well as to return for immediate medical evaluation when certain weight increases are exceeded (eg, 2 lb/d or 5 lb/wk).
Schedule periodic follow-up. Monitor symptoms, preferably using well-defined activities (eg, walking 100 ft on ground level, climbing 1-2 flights of stairs).
Follow serum levels of potassium, BUN, creatinine, AST, ALT, alkaline phosphatase, and total bilirubin. All should normalize with attainment of heart failure compensation. Failure of levels to resolve despite heart failure resolution should prompt evaluation of noncardiac sources of liver disease.
With few exceptions, patients presenting with cardiac cirrhosis and acute heart failure symptoms require hospital admission. This is particularly true in the initial presentation of heart failure.
Admission also is indicated when chronic symptoms become refractory to outpatient therapy and large doses of oral diuretics do not provide adequate diuresis.
Consider initial admission to a telemetry unit for continuous ECG monitoring.
The patient may prevent hospitalization for heart failure by enrolling in a heart failure clinic or agreeing to frequent brief physician visits for any of the following:
Reinforcing recognition of early heart failure symptoms
The independent effect of cardiac cirrhosis on morbidity or mortality rate is unknown. Prognosis is based on the patient's underlying heart failure condition.
Xiushui (Mike) Ren, MD, Cardiologist, The Permanente Medical Group; Associate Director of Research, Cardiovascular Diseases Fellowship, California Pacific Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Ronald J Oudiz, MD, FACP, FACC, FCCP, Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Director, Liu Center for Pulmonary Hypertension, Division of Cardiology, LA Biomedical Research Institute at Harbor-UCLA Medical Center
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Actelion, Bayer, Gilead, Lung Biotechnology, United Therapeutics<br/>Received research grant from: Actelion, Bayer, Gilead, Ikaria, Lung Biotechnology, Pfizer, Reata, United Therapeutics<br/>Received income in an amount equal to or greater than $250 from: Actelion, Bayer, Gilead, Lung Biotechnology, Medtronic, Reata, United Therapeutics.
Chief Editor
Henry H Ooi, MD, MRCPI, Director, Advanced Heart Failure and Cardiac Transplant Program, Nashville Veterans Affairs Medical Center; Assistant Professor of Medicine, Vanderbilt University School of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Justin D Pearlman, MD, ME, PhD, FACC, MA, Chief, Division of Cardiology, Director of Cardiology Consultative Service, Director of Cardiology Clinic Service, Director of Cardiology Non-Invasive Laboratory, Chair of Institutional Review Board, University of California, Los Angeles, David Geffen School of Medicine
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