Continuing Education Activity

Cirrhotic cardiomyopathy is a type of cardiac dysfunction that develops in patients with cirrhosis without other known cardiac diseases. It develops in up to half of patients with cirrhosis and manifests under stress. This activity reviews the evaluation and management of cirrhotic cardiomyopathy and reviews the interprofessional team's role in improving care for patients with this condition.

Objectives:

• Describe the pathophysiology of cirrhotic cardiomyopathy.
• Explain the reasons for a delayed diagnosis of cirrhotic cardiomyopathy.
• Identify the most common adverse events associated with cirrhotic cardiomyopathy.
• Review the importance of collaboration and communication amongst the interprofessional team to enhance care delivery for patients affected by cirrhotic cardiomyopathy.

Introduction

Cirrhotic cardiomyopathy (CCM) is a type of cardiac dysfunction in patients with cirrhosis without known cardiac disease. First described in 1953, CCM is characterized by an impaired cardiac response to stress, a hyperdynamic circulatory state, both diastolic and systolic dysfunctions, and various electrophysiologic abnormalities (most notably QT prolongation). This disease occurs in up to 50% of patients with cirrhosis, regardless of etiology. Alcohol use disorder and hemochromatosis are additional risk factors in the development of cardiac disease. As CCM manifests under stress, it remains an under-recognized condition, and no standardized treatment regimen has yet been established. A significant improvement, or reversal, of CCM has been noted in patients after liver transplantation.[1][2][3]

Etiology

Cirrhotic cardiomyopathy is due to cirrhosis, regardless of its cause. However, patients with alcohol use disorder and hemochromatosis have additional contributing factors for cardiac dysfunction. There is a direct correlation between the severity of the liver disease, as indicated by the Model For End-Stage Liver Disease (MELD) score and the degree of cardiomyopathy. No genetic predisposition for CCM has been identified.[4][5]

Epidemiology

As patients with cirrhotic cardiomyopathy are generally asymptomatic with near-normal cardiac function, except during periods of stress, the exact prevalence of this disease is difficult to determine. It is estimated that myocardial compromise is present in up to 50% of patients with cirrhosis. Most patients with moderate to advanced cirrhosis (Child-Pugh Class B or C) will present with at least one feature of CCM, such as QT prolongation or diastolic dysfunction. Among patients with cirrhosis undergoing liver transplantation, almost 50% have been observed to develop signs of cardiac dysfunction within the peri-operative period, with 7% to 21% mortality from heart failure in the months following transplant. Limited studies have indicated that CCM is more common in males, people over 50-years-old, and in patients with cirrhosis secondary to alcohol abuse.[6][7]

Pathophysiology

Cirrhotic cardiomyopathy is characterized by an impaired cardiac response to stress, which results from a combination of autonomic dysfunction, alterations in cell membrane composition, ion channel defects, and an overproduction of cardio depressant factors. Patients with cirrhosis have effective central hypovolemia, despite an absolute volume overload, due to splanchnic vasodilation caused by the production of nitric oxide, carbon monoxide, and endocannabinoids. (This splanchnic vasodilation results in a decrease in systemic vascular resistance, initially compensating for cardiac dysfunction and producing an asymptomatic clinical picture at rest.) The state of functional hypovolemia activates the renin-angiotensin-aldosterone system and the sympathetic nervous system, which chronically leads to the downregulation of beta-adrenergic receptors in the plasma membrane with resultant autonomic dysfunction.

Patients with cirrhosis are also noted to have elevations in cell membrane cholesterol content, altering membrane fluidity and disrupting the number and function of receptors. The decrease in L-type calcium channels and potassium channels increases action potential duration and leads to QT prolongation. Additionally, the dysregulation of Na/Ca channels leads to massive calcium influx into cells and stimulates cardiomyocyte apoptosis. The combination of prolonged action potentials, resulting in impaired myocyte relaxation and alteration of titin and collagen configurations, produces eccentric left ventricular hypertrophy and diastolic dysfunction. Systolic dysfunction will eventually develop due to impaired energy metabolism and reduced myocardial reserve.[8]

Histopathology

Histologic changes of myocardial cells in cirrhotic cardiomyopathy include fibrosis, subendocardial edema, and vacuolation of the nucleus and cytoplasm. However, these findings are non-specific and are similar to cellular changes observed in alcoholic cardiomyopathy.

History and Physical

Cirrhotic cardiomyopathy is clinically asymptomatic in most patients as peripheral vasodilation reduces afterload and compensates for abnormal cardiac function. In times of stress, rapid hemodynamic changes with impaired cardiac response will produce acute heart failure symptoms. CCM should be suspected in patients with moderate-to-advanced cirrhosis (Child-Pugh Class B or C) presenting with exercise intolerance, worsening fatigue, and/or peripheral edema who have no known history of cardiac disease. As these symptoms are non-specific and can be attributed to advancing cirrhosis, CCM is frequently under-recognized and misdiagnosed.

Physical exam findings will often be unremarkable for cardiopulmonary disease. In the setting of physiologic, pharmacologic, or pathologic stress, signs of congestive heart failure may become apparent. Classic physical exam findings, including peripheral edema, jugular venous distention, and third and/or fourth heart sounds, will likely be present. During a physical examination, classic signs of liver disease, such as jaundice, scleral icterus, ascites, and hepatomegaly, should be noted.[9]

Evaluation

The first and most widely accepted diagnostic criteria for cirrhotic cardiomyopathy were proposed during the 2005 World Congress of Gastroenterology (WCG) in Montreal. This criterion includes evidence of systolic dysfunction (blunted increase in cardiac output with physiologic or pharmacologic stimuli and left ventricular ejection fraction less than 55%), evidence of diastolic dysfunction (ratio of early to atrial flow velocities (E/A) less than 1, mitral deceleration time over 200 milliseconds, and isovolumetric relaxation time over 80 milliseconds), and the presence of various supportive criteria (electrophysiological abnormalities, enlarged left atrium, increased left ventricular wall thickness, increased brain-type natriuretic peptide, and increased troponins).

Initial lab work should confirm cardiac involvement and include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), or its prohormone N-terminal pro-BNP (NT-proBNP), and troponin I. If available, a galectin-3 level can be obtained as a marker of cardiac fibrosis.

QT prolongation on electrocardiogram (EKG) is often the first sign of CCM. This has been noted to vary between daytime and nighttime due to diurnal variations in the autonomic nervous and circulatory systems.

The chest x-ray is typically normal but may show cardiomegaly and pulmonary edema.

Echocardiography showing diastolic and/or systolic dysfunction is essential for diagnosis. Speckle tracking can be used to analyze the ventricular function further.

As CCM manifests under conditions of stress, a chemical or exercise stress test demonstrating a blunted cardiac response can be useful in confirming this diagnosis.[10][11]

Treatment / Management

Currently, there is no standardized protocol or specific medications available for the treatment of cirrhotic cardiomyopathy. Patients should receive standard medical therapy for the management of heart failure and undergo evaluation for liver transplantation.

Medical therapy will generally include angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), loop and thiazide diuretics, aldosterone receptor antagonists, and beta-blockers. ACE inhibitors are known to reduce morbidity and mortality in patients with heart failure but are not recommended in patients with Child-Pugh classes B or C due to the potential to exacerbate systemic vasodilation and increase the risk of hepatorenal syndrome. Loop and thiazide diuretics are used for the management of hypervolemia and represent key elements of treatment. Aldosterone receptor antagonists are used to improve hemodynamics in patients with CCM by curtailing the continuous activation of the renin-angiotensin-aldosterone system. At presentation, patients with cirrhosis are already likely to be taking beta-blockers to reduce portal hypertension and prevent variceal bleeding. Non-specific beta-blockers, in particular carvedilol, have been suggested to more effective in reducing portal hypertension and have been shown to reduce QT prolongation.

Transjugular intrahepatic portosystemic shunt (TIPS) placement is used to reduce portal hypertension in patients with cirrhosis, but this procedure is not expected to improve cardiomyopathy.

As CCM develops due to cirrhosis, liver transplantation is the cornerstone of treatment. Transplantation has been shown to significantly improve systolic and diastolic dysfunction and reverse QT prolongation in 50% of patients. Cardiac benefits are observed within 3 to 12 months following surgery. The extent of cardiac normalization following liver transplantation is currently unknown.[12][13][14]

Differential Diagnosis

• Alcoholic cardiomyopathy
• Other dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Restrictive cardiomyopathy

Prognosis

Overall, cirrhosis is associated with an unfavorable prognosis, which worsens with the development of cirrhotic cardiomyopathy. The presence of left ventricular diastolic dysfunction (LVDD) and a Child-Pugh score above 8 is associated with a poorer prognosis. In one study, one-year survival in patients with cirrhosis without LVDD was 95%, which decreased to 79% and 39% with grade I and grade II LVDD, respectively. While definitive treatment for CCM is liver transplantation, up to a quarter of patients with cirrhosis will experience postoperative cardiovascular complications, with 7% to 21% total mortality following liver transplantation attributable to cardiovascular causes.[15]

Complications

• Congestive heart failure
• Arrhythmias
• Pulmonary hypertension
• Hepatorenal syndrome
• Sudden cardiac death

Consultations

• Cardiology
• Gastroenterology

Deterrence and Patient Education

Patient education on medication compliance, dietary restrictions (including sodium restriction), regular follow-ups, requirements for liver transplantation, and recognition of symptoms of acute heart failure are essential for management.

Enhancing Healthcare Team Outcomes

Cirrhotic cardiomyopathy is an under-recognized condition that carries a poor prognosis. As this disease develops due to cirrhosis, early recognition and management of conditions predispose to liver disease is key. This requires the efforts of an interprofessional healthcare team. Primary care physicians and mid-level providers should monitor patients for alcohol use disorder, screen for hepatitis, and encourage lifestyle modifications in patients at risk for non-alcoholic fatty liver disease (NAFLD). Early referral to gastroenterology may be appropriate for patients with genetic or immune conditions, such as Wilson’s disease or autoimmune hepatitis. A high suspicion for CCM is necessary for patients with known cirrhosis as presenting symptoms are non-specific, and no screening guidelines exist. Gastroenterology, or hepatology, will be involved in the management of cirrhosis. Pharmacists will help monitor medication therapy, advise on potential adverse effects, and check for drug-drug interactions. Nursing staff can serve as the initial point for patient counseling and answering questions. If the patient is determined to be a liver transplant candidate, a transplant team should be involved early on. Cardiology should follow these patients to monitor cardiomyopathy and tailor medical regimens. A dietary referral may also be helpful for patient education on fluid and sodium restriction. The involvement of an interprofessional team with effective communication is essential for managing any patient with CCM. [Level 5]