Liver transplantation (LT) is considered the only definitive therapy for decompensated cirrhosis or severe acute liver failure that can improve the expected lifespan and quality of life [1]. Despite improvements in hemodynamic monitoring devices and anesthetic techniques, LT remains an extremely challenging procedure for anesthesiologists. Not only does the procedure itself pose a high risk of massive blood loss [2], but patients with end-stage liver disease (ESLD) are frequently accompanied by many conditions that contribute to hemodynamic instability, such as cirrhotic cardiomyopathy (CCM), pericardial effusion, coronary artery disease (CAD), portopulmonary hypertension (PoPH), electrolyte derangements, and large amounts of ascites [3-5].

Echocardiography is a powerful tool that directly visualizes the structural and functional status of the heart in real-time at the bedside [5]. Transthoracic echocardiography (TTE) is a non-invasive cardiac investigation technique that obtains images from the surface of the body through four acoustic windows: parasternal, apical, subcostal, and suprasternal notch [6]. Transesophageal echocardiography (TEE) is a semi-invasive imaging tool in which the probe is inserted into the esophagus, and images are obtained through the esophagus and stomach [7]. Moreover, echocardiography provides more reliable measures than traditional pressure-based indicators such as pulmonary artery occlusion pressure and central venous pressure. It also has a high diagnostic value for detecting systolic or diastolic dysfunction, wall motion abnormalities, valvular dysfunction, hypovolemia, volume overload, left ventricular outflow tract obstruction (LVOTO), pericardial abnormalities, intracardiac air, and thrombus [5,8]. Echocardiography is gaining popularity and is becoming more broadly adopted due to these advantages. TTE is recommended for all LT candidates by the American Association for the Study of Liver Diseases (AASLD) [1]. According to the American Society of Echocardiography (ASE) guidelines, the usefulness of intraoperative TEE during LT is supported by a grade B2 level of evidence [9], and TEE has already been widely utilized during LT in the United States [10]. In contrast, the use of pulmonary artery catheterization has decreased even though it is still recommended and useful [11].

Although anesthesiologists cannot fully play the role of cardiologists, perioperative echocardiography is still a feasible and useful option, considering that it provides additional accurate and detailed assessments that could affect patient management strategies with minimal or no risk to the patient. Perioperative echocardiography by anesthesiologists is especially helpful when performing emergency operations because the ability to complete a comprehensive preoperative evaluation of patients is unlikely [12,13]. As the majority of liver transplants are from deceased donors worldwide, most are likely to be emergency cases. Therefore, perioperative echocardiography by anesthesiologists seems a useful tool. Although in Korea, 75.2% of the LT were performed with livers from living donors in 2019, deceased donor LT still accounted for 24.8% of the cases, which is not a negligible number [14].

Cirrhosis results from hepatic inflammation, fibrogenesis, angiogenesis, and loss of parenchymal cells. Structural and functional abnormalities of the liver lead to increased hepatic resistance and portal hypertension, which underlie most of the complications and mortality in patients with cirrhosis [15]. Subsequently, systemic vasodilation occurs mainly in the splanchnic vasculature bed because of increased circulating endothelial vasodilators from enhanced release and impaired degradation [16]. Decreased peripheral vascular resistance is initially compensated for by increased cardiac output, forming a characteristic circulatory status in patients with ESLD known as hyperdynamic circulation [17]. Relative arterial underfilling also stimulates baroreceptors and causes expansion of plasma volume with activation of the neurohumoral axis, including the renin-angiotensin-aldosterone system (RAAS), sympathetic nerve system (SNS), and arginine vasopressin [18]. Prolonged alterations in hemodynamic status and subsequent structural and functional changes in the heart could contribute to the development of CCM [19].

These cardiovascular abnormalities, typically accompanied by cirrhosis, can be diagnosed as cirrhotic cardiomyopathy when they are severe enough to meet certain criteria. CCM refers to a pathological cardiac condition in patients with ESLD in the absence of prior heart disease [43]. Initially believed to be the result of direct cardiac toxicity of alcohol in the 1950s, it was named for the first time in 1989 as ‘cirrhotic cardiomyopathy’ and started to be perceived as a syndrome of cardiac dysfunction in ESLD patients [55,56]. It was more clearly defined at the Montreal 2005 World Congress of Gastroenterology as an impaired contractile response to stress and/or diastolic dysfunction with electrophysiological abnormalities. In addition, diagnostic criteria for CCM have been proposed [40]. Recently, updated criteria with modern concepts of heart failure were proposed by a multidisciplinary expert group called the CCC in 2019 (Table 1) [43].

Heart failure is an important cause of death, accounting for 7-21% of post-LT mortality. Heart failure is also one of the leading causes of hospital admissions, accounting for 24% of admissions within 90 days of LT in the United States [57]. CCM is quite common and is believed to be present in approximately half of cirrhotic patients without symptoms at rest [58]. However, under conditions that impose physiological or pharmacological stress on the heart with CCM, such as infections, transjugular intrahepatic portosystemic shunt, and surgical stimuli during LT, cardiac dysfunction may be unmasked and progress to overt heart failure. Normalization of peripheral vasodilation in the post-LT period could also be a stressor in the heart with increased afterload and cause post-LT heart failure [32,33]. Moreover, the association between CCM and other conditions such as HRS and increased mortality and/or morbidity after therapeutic procedures has been observed in several studies [51]. Considering its high prevalence and harmful effects, it is a noteworthy complication that should be investigated prior to LT surgery.

The diagnostic criteria for CCM consist of three categories: systolic dysfunction, diastolic dysfunction, and other supportive criteria. In the 2005 Montreal criteria, systolic dysfunction was diagnosed when any of the following criteria were met: blunted contractile response on stress testing or LVEF < 55%. However, the usefulness of these criteria has been questioned for several reasons. First, there is no universally accepted definition of blunted contractile response. Second, stress testing is often limited or possibly confounded by factors such as the common use of β-adrenergic antagonists and the inability to perform exercise stress tests. Third, subclinical systolic dysfunction can be masked by decreased afterload due to the vasodilatory state of patients with cirrhosis. Fourth, together with the reasons mentioned above, additional parameters other than LVEF have been used to evaluate cardiac functional reserve. Considering these, the 2019 CCC guideline re-defined systolic dysfunction as when any of the following is present: LVEF ≤ 50%, absolute GLS < 18%, or > 22% [43]. GLS was included as it seems to be a more sensitive parameter of systolic function and a superior predictor of cardiac events and mortality than LVEF. In addition, it is relatively less dependent on loading conditions than LVEF [59,60]. Although there are limitations in that GLS is affected by age, sex, and loading condition, and only limited and conflicting evidence for the use of GLS in detecting CCM with normal LVEF is present, it is still believed to play a role in detecting subclinical systolic dysfunction in cirrhotic patients. Downward adjustment of the LVEF cut-off value from 55% to 50% was made without any detailed description in the article but was seemingly done to reflect normal values in the general population [43]. However, some researchers have questioned the validity of adjusted LVEF cut-off values based on post-LT mortality [61].

According to the 2005 Montreal criteria, diastolic dysfunction was diagnosed when any of the following criteria were met: deceleration time > 200 ms, isovolumetric relaxation time > 80 ms, or E/A < 1. However, these parameters can be affected by loading conditions and heart rate. In addition, a U-shaped relationship with the degree of diastolic dysfunction renders it difficult to distinguish between advanced and normal function [43]. Relatively new guidelines for the assessment of diastolic dysfunction were issued in 2016 by the ASE/EACVI. These guidelines have two different algorithms for screening and grading. To screen for diastolic dysfunction, the guidelines recommend four parameters: septal e,’ the ratio of E to e’ of the medial wall or average, TR velocity, and LAVI. For grading, E/A was used instead of septal e’ velocity [42]. To simplify and integrate the two algorithms, Oh et al. [62] proposed a revised unified version that was adopted in the 2019 CCC criteria. In the 2019 CCC criteria, patients who met more than three of the following criteria were diagnosed as having advanced (grade II or III) diastolic dysfunction: septal e’ velocity < 7 cm/s, E/e’ ratio ≥ 15, LAVI > 34 ml/m² and TR velocity > 2.8 m/s. Notably, primary pulmonary hypertension or PoPH should be ruled out before applying the TR velocity criterion [43]. Compared to previous guidelines, the 2016 ASE/EACVI is considered simpler and more specific, with a significantly lower prevalence of diastolic dysfunction. However, there is a concern about the possibility that updated guidelines can only detect advanced cases [63]. The increased specificity of the 2016 ASE/EACVI guidelines was also observed in cirrhotic patients undergoing LT [64].

A number of features not included in both the systolic and diastolic function sections were classified as supportive criteria in the 2005 Montreal criteria. In the 2019 CCC criteria, the supportive criteria section was replaced by ‘Area for Future Research Which Requires Further Validation.’ Although the names and classifications of features have changed, they seem to include roughly similar content, except for several updates. The blunted contractile response has moved from the systolic dysfunction section to an area for future research, which requires further validation because of the limitations mentioned above. Electrophysiological abnormalities, including prolonged QTc interval, are no longer considered to have significant diagnostic value for CCM, with prevalence as high as 50% in cirrhosis and suspicious predictive power for poor outcomes. Serum biomarkers are recommended to be helpful when used in conjunction with imaging studies. A variety of biomarkers, such as nitric oxide, endothelin, copeptin, endocannabinoids, interleukins, and galectin-3, have been proposed as potentially useful parameters in the future. However, further studies are required to confirm their clinical application. In addition, previously recommended biomarkers, brain natriuretic peptide, pro-peptide N-terminal prohormone of BNP, and T- and I-troponin, are still recognized for their clinical importance with their ability to reflect the severity of cirrhosis and cardiac dysfunction and predict morbidity and mortality. Cardiac magnetic resonance imaging is newly included in the criteria because it appears to have diagnostic value for subclinical myocardial dysfunction and provides a comprehensive evaluation [43].

Studies on CCM reported its prevalence to be 46-63% in cirrhosis patients when the 2005 Montreal criteria were applied. Razpotnik et al. [58] conducted a study to compare the prevalence of CCM in 122 patients with cirrhosis using different criteria. They found that the overall prevalence was slightly higher with the 2005 Montreal criteria than the 2019 CCC criteria. However, the results differed remarkably between the two criteria when systolic and diastolic dysfunctions were analyzed separately. When the 2019 CCC criteria were applied, the prevalence of systolic dysfunction was higher (16.4% vs. 53.3%), while diagnostic dysfunction was lower (64.8% vs. 6.4%), reflecting the increased specificity of 2016 ASE/EACVI guidelines for diastolic dysfunction and more sensitive detection of subclinical systolic dysfunction by the implementation of GLS [58].

There are many pathological conditions accompanied by cirrhosis that can harmfully affect hemodynamic stability, as well as typical cardiovascular abnormalities, including CCM.

Intraoperative hemodynamic instability during LT is associated with various contributing factors. Intraoperative blood loss is one of the most common and important risk factors. LT frequently results in massive blood loss. A recent study investigated 108 LT patients with an average intraoperative blood loss of 1,505.8 ml. Blood loss of more than 1,000 ml was observed in 72.2% of cases and more than 2,000 ml in 14.8% [109]. Although several possible predictors have been suggested, massive blood loss is still considered unpredictable with conflicting and inconsistent results. Therefore, sufficient intravenous access and blood products should be prepared before surgery [110]. The aforementioned abdominal decompression by drainage of ascites and opening of the abdomen may also contribute to decreased preload with vasodilation and reaccumulation of ascites [4,107]. Intraoperative manipulation of the inferior vena cava (IVC), including clamping of the IVC during the anhepatic phase and release for reperfusion, is another major contributor to abrupt changes in the preload during surgery. During clamping of the IVC, the significantly decreased preload should be replaced with fluid resuscitation to maintain hemodynamic stability. However, a decrease in preload is transient, and excessive fluid infusion may result in worsened hemodynamic instability, especially in the setting of right ventricular dysfunction [111]. Fluid overload is strongly associated with postoperative pulmonary complications [112]. In addition to fluid infusion, the transfusion of blood products is associated with pulmonary complications through transfusion-associated circulatory overload and transfusion-related acute lung injury [113]. Therefore, judicious fluid infusion and transfusion are required, and intraoperative TEE can be useful for guiding fluid infusion and transfusion when used in conjunction with hemodynamic parameters [114,115]. The reperfusion phase, which starts with unclamping of the IVC, is considered the most critical stage of LT in which major hemodynamic events are frequently encountered. Post-reperfusion syndrome (PRS) refers to an event that presents as severe hypotension, bradycardia, and low systemic vascular resistance within 5 min after unclamping. Cold, acidic, hyperkalemic blood that contains vasoactive inflammatory substances from ischemic grafts is thought to be responsible for PRS [116]. The relationship between PRS and CCM is not yet clear, with insufficient and inconsistent data. However, one study demonstrated a correlation between diastolic dysfunction and PRS, indicating a possible association [117]. These intraoperative hemodynamic instabilities and metabolic changes impose remarkable stress on the recipient’s heart. As shown by the association mentioned above between cardiac dysfunction and adverse outcomes, cirrhotic patients with cardiac dysfunction may be more vulnerable to such stress. Unfortunately, there is no reliable method for identifying LT candidates with a high risk of perioperative cardiac complications.

Cardiovascular abnormalities are frequently observed in patients with ESLD. Although LT is the only definitive therapy for ESLD, LT imposes remarkable stress on the heart, such as rapid hemodynamic changes and metabolic disturbances. As a result of underlying pathological conditions and acute stressful stimuli, cardiovascular complications account for a considerable portion of perioperative morbidity and mortality in LT recipients. Echocardiography is a powerful non- or semi-invasive tool that directly visualizes the structural and functional state of the heart, such as chamber sizes, systolic and diastolic function, valvular function, and pulmonary artery pressure. It can be used to evaluate the heart condition prior to surgery and intraoperatively to assess hemodynamic status. The usefulness of echocardiography can be inferred from the fact that the AASLD recommends the preoperative use of TTE for all candidates, and the ASE recommends intraoperative TEE with a grade B level of evidence. We recommend the use of preoperative TTE and intraoperative TEE for LT, if not contraindicated. CAG or coronary computed tomography angiography should be considered in patients with a high risk of CAD, as stress echocardiography is often limited. Broader application of echocardiography and further research would be able to improve LT outcomes in the future.