Cirrhotic Cardiomyopathy

Cirrhotic cardiomyopathy (CCM) is a clinical syndrome in cirrhotic patients characterized by impaired contractile reserve in response to stress and/or altered diastolic function along with electrophysiological abnormalities in the absence of other known cardiac disease.
•CCM is a separate clinical entity from alcoholic cardiomyopathy.

Synonym

Epidemiology & Demographics

Incidence and Prevalence

•Prevalence between 40% to 50% in cirrhotic patients (based on the 2005 definition of CCM) independent of liver disease etiology and 3% to 23.4% of patients undergoing orthotopic liver transplantation.
•Cardiac dysfunction is seen in 50% of patients with advanced cirrhosis.
•Heart failure occurs in 7% to 21% of patients who undergo orthotopic liver transplantation.

What increases the Risk of Cirrhotic Cardiomyopathy?

•Moderate to severe cirrhosis (Child Pugh B or C) tends to have at least one feature of CCM. There is no direct correlation between the degree of liver cirrhosis (assessed by Child Pugh or MELD score) and CCM.
•Posttransjugular intrahepatic portosystemic shunt (TIPS): Increased left ventricular preload secondary to the shift of splanchnic blood via the artificial shunts overloading a noncompliant left ventricle, leading to overt heart failure.

What are the Symptoms of Cirrhotic Cardiomyopathy?

Physical Findings & Clinical Presentation

Clinical and physical features include:

•Symptoms and signs of heart failure: Reduced exercise capacity, dyspnea on exertion, tachycardia, edema, ascites, paroxysmal nocturnal dyspnea, pulmonary congestion, increased jugular venous pressure and/or hepato-jugular reflex, and an S3 or S4 gallop
•Electrophysiological disturbances: QTc interval prolongation (>440 msec), Torsade de pointes, chronotropic incompetence

Etiology & Pathophysiology

Etiology is multifactorial in patients with liver disease.

Mechanisms of cardiac dysfunction include the following:

•Increased catecholamines in cirrhotic patients eventually leads to the downregulation of β-adrenergic receptors resulting in attenuated inotropic and chronotropic function.
•Inflammatory stimuli from nitric oxide, carbon monoxide, endocannabinoids, and cytokines, such as TNF-a, increase cardiomyocyte apoptosis.
•Impaired metabolic function of the liver with decreased degradation of certain proteins.
•The decreased effective volume activates the renin–angiotensin–aldosterone system (RAAS), leading to fibrosis and stiff ventricles.
•Myocyte membrane changes: Potassium channel defect leads to electrophysiological imbalances such as QT prolongation, chronotropic incompetence, and mechanical dyssynchrony.
•Hyperdynamic circulation: Increased volume expansion but with poor volume distribution (increased splanchnic circulation, decreased central circulation) leads to a decrease in the effective circulating blood volume, which activates the RAAS and sympathetic nervous system and leads to tachycardia and increased cardiac output.

Diagnosis

The 2005 World Congress of Gastroenterology proposed the following criteria for CCM:

•Systolic dysfunction (LV EF <55%, blunted increase in cardiac output with exercise)
•Diastolic dysfunction on echocardiogram (E/A <1.0, deceleration time >200 msec, isovolumetric relaxation time >80 msec)
•Supportive criteria: Electromechanical abnormalities (prolonged QTc), heart chamber alterations (enlarged left atrium), humoral changes (increased brain natriuretic peptide [BNP], N-terminal pro-BNP [NT pro-BNP], or troponin)

The 2019 proposed criteria by the Cirrhotic Cardiomyopathy Consortium:

•Systolic dysfunction (LVEF < 50% or Absolute GLS <-18% or >-22%
•Diastolic dysfunction (≥ 3 of the following): Tissue Doppler velocities with septal e’< 7 cm/s, E/e’ > 14, left atrial size (LAVI > 34 ml/m²) and tricuspid regurgitation jet (TR velocity > 2.8 m/s).

Differential Diagnosis

•Alcoholic cardiomyopathy (ACM)
•Cardiac cirrhosis-congestive hepatopathy
•Iron-induced cardiac disease (hemochromatosis)
•Dilated cardiomyopathy
•Hypertrophic cardiomyopathy
•Restrictive cardiomyopathy
•Coronary atherosclerosis with left ventricular dysfunction
•Porto-pulmonary hypertension

Workup

•BNP and NT pro-BNP: Markers of fluid overload, can correlate with the severity of cirrhosis
•Troponin I or T: Assess cardiac ischemia, increased LV mass

Imaging Studies

•Electrocardiography: QTc >440 msec, ST depressions, bundle branch block
•Chest x-ray: Pulmonary congestion, left atrial and ventricular enlargement
•Echocardiogram: Resting systolic dysfunction, diastolic dysfunction, and tricuspid regurgitation.
•MRI: Morphological evaluation of the liver and the heart (shunts, chamber quantification, tissue characterization, myocardial extracellular volume)

Diagnostic Tests

•Exercise testing (upright bicycle ergometry): Suppressed increase in cardiac output with exercise.
•Dobutamine stress echocardiography (DSE): Lack of contractile reserve with dobutamine defined as an increase in LV EF <10% and/or diastolic dysfunction. DSE has limited utility due to downregulated β-receptors. Atropine might play a role in achieving target heart rate.
•Cardiopulmonary exercise testing: Assess candidacy for concomitant heart transplantation.

Treatment

There are no well-established guidelines for the management of CCM. Management should follow the same guidelines as in noncirrhotics.

Nonpharmacologic Therapy

•Risk-factor modification: Weight loss, smoking cessation, exercise, blood pressure control
•Oxygen supplementation if signs of hypoxia
•Dietary sodium restriction (<2 g/day)
•Fluid restriction when serum sodium <120 mmol/L
•Pneumococcal and influenza vaccination

Acute General Rx

•Acute pulmonary edema: Head elevation ≥30 degrees, early diuretic use (furosemide, bumetanide, torsemide); nitrates are useful if concomitant hypertension or chest pain.
•Cardiogenic shock: Inotropes (dobutamine, milrinone), vasopressors (norepinephrine, dopamine), and mechanical support if needed. Avoid nitroprusside for afterload reduction as cirrhotic patients are at higher risk of cyanide toxicity.

Chronic Rx

Chronic management is consistent with the treatment of patients with heart failure.

•Diuretics: Furosemide and spironolactone are the mainstay for treating fluid overload in cirrhosis.
•Beta-blockers: They promote the reduction of the QT interval. Nonselective beta-blockers are known to prevent variceal bleeding. One should exercise with caution because beta-blockers can reduce cardiac output.
•Liver transplantation is the cure for cirrhosis and its associated cardiomyopathy. It has been shown to restore exercise capacity within 6 to 12 mo.
•Orthotopic combined heart and liver transplantation should be considered if indicated.

Disposition

•Mortality rate is unclear because most patients die from repercussions of liver failure.
•Liver transplant can reverse CCM features, including systolic and diastolic dysfunction and QT prolongation.
•Patients with diastolic dysfunction have worse prognosis after liver transplantation.

Referral

Follow-up with a cardiologist is recommended.

Pearls & Considerations

Comments

•CCM should be considered in cirrhotic patients who present with symptoms and signs of heart failure or arrhythmia.
•Diagnostic criteria are based on physical exam, echocardiogram (systolic or diastolic dysfunction), stress testing, electrophysiological disturbances, and laboratory abnormalities.
•Liver transplantation is the definitive treatment for this rare clinical entity.

Prevention

Treatment of liver disease prior to progression to cirrhosis

Patient & Family Education

A multidisciplinary team involving a hepatologist and cardiologist may be useful in long-term management and patient education.

Seek Additional Information

Carvalho M.V.H., et al.: Cirrhotic cardiomyopathy: the liver affects the heart. Braz J Med Biol Res 2019; 52 (2): pp. e7809.
Enache I., et al.: Cirrhotic cardiomyopathy and hepatopulmonary syndrome: prevalence and prognosis in a series of patients. Respir Med 2013; 107: pp. 1030-1036.
Izzy M., et al.: Redefining cirrhotic cardiomyopathy for the modern era. Hepatology 2020; 71 (1): pp. 334-345.
Møller S., et al.: An update on cirrhotic cardiomyopathy. Expert Rev Gastroenterol Hepatol 2019; 13 (5): pp. 497-505.
Páll A., et al.: Pathophysiological and clinical approach to cirrhotic cardiomyopathy. J Gastrointestin Liver Dis 2014; 23 (3): pp. 301-310.
Sampaio F., et al.: Left ventricular function assessment in cirrhosis: current methods and future directions. World J Gastroenterol 2016; 22 (1): pp. 112-125.
Silvestre O., et al.: β-Blocker therapy for cirrhotic cardiomyopathy: a randomized-controlled trial. Eur J Gastroenterol Hepatol 2018; 30 (8): pp. 930-937.
Zardi E.M., et al.: Cirrhotic cardiomyopathy. J Am Coll Cardiol 2010; 56 (7): pp. 539-549.

Cirrhotic Cardiomyopathy