Diagnosis and Management of Cirrhotic Cardiomyopathy

Abstract

Background: Cirrhotic cardiomyopathy refers to the structural and functional changes in the heart leading to either impaired systolic, diastolic, electrocardiographic, and neurohormonal changes associated with cirrhosis and portal hypertension. Cirrhotic cardiomyopathy is present in 50% of patients with cirrhosis and is clinically seen as impaired contractility, diastolic dysfunction, hyperdynamic circulation, and electromechanical desynchrony such as QT prolongation. In this review, we will discuss the cardiac physiology principles underlying cirrhotic cardiomyopathy, imaging techniques such as cardiac magnetic resonance imaging and scintigraphy, cardiac biomarkers, and newer echocardiographic techniques such as tissue Doppler imaging and speckle tracking, and emerging treatments to improve outcomes.

Methods: We reviewed available literature from MEDLINE for randomized controlled trials, cohort studies, cross-sectional studies, and real-world outcomes using the search terms "cirrhotic cardiomyopathy," "left ventricular diastolic dysfunction," "heart failure in cirrhosis," "liver transplantation," and "coronary artery disease".

Results: Cirrhotic cardiomyopathy is associated with increased risk of complications such as hepatorenal syndrome, refractory ascites, impaired response to stressors including sepsis, bleeding or transplantation, poor health-related quality of life and increased morbidity and mortality. The evaluation of cirrhotic cardiomyopathy should also guide the feasibility of procedures such as transjugular intrahepatic portosystemic shunt, dose titration protocol of betablockers, and liver transplantation. The use of targeted heart rate reduction is of interest to improve cardiac filling and improve the cardiac output using repurposed heart failure drugs such as ivabradine. Liver transplantation may also reverse the cirrhotic cardiomyopathy; however, careful cardiac evaluation is necessary to rule out coronary artery disease and improve cardiac outcomes in the perioperative period.

Conclusion: More data are needed on the new diagnostic criteria, molecular and biochemical changes, and repurposed drugs in cirrhotic cardiomyopathy. The use of advanced imaging techniques should be incorporated in clinical practice.

Keywords: 2-AG, 2-arachidonylglycerol; 2D, two-dimensional; AEA, Anandamide; ANP, Atrial Natriuretic Peptide; ASE, the American Society of Echocardiography; AUC, area under the curve; BA, bile acid; BNP, Brain natriuretic peptide; CAD, coronary artery disease; CB-1, cannabinoid −1; CCM, Cirrhotic Cardiomyopathy; CMR, cardiovascular magnetic resonance imaging; CO, cardiac output; CT, computed tomography; CTP, Child–Turcotte–Pugh; CVP, central venous pressure; DT, deceleration Time; ECG, electrocardiogram; ECV, extracellular volume; EF, Ejection fraction; EMD, electromechanical desynchrony; ESLD, end-stage liver disease; FXR, Farnesoid X receptor; GI, gastrointestinal; GLS, Global Longitudinal strain; HCN, Hyperpolarization-activated cyclic nucleotide–gated; HE, hepatic encephalopathy; HF, heart failure; HO, Heme oxygenase; HPS, hepatopulmonary syndrome; HR, heart rate; HRS, hepatorenal syndrome; HVPG, hepatic venous pressure gradient; HfmrEF, heart failure with mid-range ejection fraction; HfrEF, heart failure with reduced ejection fraction; IVC, Inferior Vena Cava; IVCD, IVC Diameter; IVS, intravascular volume status; L-NAME, NG-nitro-L-arginine methyl ester; LA, left atrium; LAVI, LA volume index; LGE, late gadolinium enhancement; LT, liver transplant; LV, left ventricle; LVDD, left ventricular diastolic dysfunction; LVEDP, left ventricular end-diastolic pressure; LVEDV, LV end diastolic volume; LVEF, left ventricular ejection fraction; LVESV, LV end systolic volume; LVOT, left ventricular outflow tract; MAP, mean arterial pressure; MELD, Model for End-Stage Liver Disease; MR, mitral regurgitation; MRI, Magnetic resonance imaging; MV, mitral valve; NAFLD, Nonalcoholic fatty liver disease; NO, nitric oxide; NOS, Nitric oxide synthases; NTProBNP, N-terminal proBNP; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedged pressure; PHT, portal hypertension; PWD, Pulsed-wave Doppler; RV, right ventricle; RVOT, right ventricular outflow tract; SA, sinoatrial; SD, standard deviation; SV, stroke volume; SVR, Systemic vascular resistance; TDI, tissue Doppler imaging; TIPS, transjugular intrahepatic portosystemic shunt; TR, Tricuspid valve; TRPV1, transient receptor potential cation channel subfamily V member 1; TTE, transthoracic echocardiography; USG, ultrasonography; VTI, velocity time integral; beta blocker; cirrhotic cardiomyopathy; hemodynamics in cirrhosis; left ventricular diastolic dysfunction.

© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1

Diagnostic criteria and pathophysiological mechanisms of cirrhotic cardiomyopathy.

Figure 2

Echocardiographic assessment of left ventricular diastolic dysfunction (LVDD) using tissue Doppler imaging. E: transmitral flow velocity during early ventricular filling; A, transmitral flow velocity during atrial contraction; e’ Tissue Doppler velocity at the mitral annulus during early ventricular filling.

Figure 3

Schematic representation of the molecular events in the cardiac myocyte. Panel A: Channels and signaling pathways in the myocardium: β1-Adrenergic receptor stimulation leads to interaction with G protein; then, a cascade of events from adenylyl cyclase activation leads to the phosphorylation of ion channels. Phosphorylation of the Ca channels ultimately leads to cross-bridging of myosin and actin and, therefore, myocyte contraction. The myosin heavy chain is linked to actin after activation of the troponin I, T and C complex after the influx of Ca 2+. Phosphorylation of Na channels favors depolarization of phase 4 of the action potential, ultimately leading to heart rate acceleration. Several receptor and channel abnormalities have been described in cirrhosis, that account for reduced contractility, chronotropic incompetence, and electromechanical uncoupling. Inset Panel B: Cardiac pacemaker current (If), a mixed sodium-potassium inward current that controls the spontaneous diastolic depolarization in the sinoatrial (SA) node and hence regulates the heart rate. β, β 1-adrenergic receptor; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; G, G protein; I Ca-L, slowly decaying inward Ca2-L current; INa–B, inward Na background leak current.

Figure 4

Diagnostic algorithm and drug targets in cirrhotic cardiomyopathy.