Role of Pretransplant Echocardiographic Evaluation in Predicting Outcomes Following Liver Transplantation



Maintenance of cardiac function is critical to the survival of patients with end-stage liver disease after liver transplantation (LT). We sought to determine whether pre-LT echocardiographic indices of right heart structure and function were independently predictive of morbidity and mortality post-LT. We retrospectively studied 216 consecutive patients who underwent pre-LT 2-dimensional/Doppler echocardiography with subsequent LT from 2007 to 2010. A blinded reader analyzed multiple echocardiographic parameters, including right ventricular structure and function, pulmonary artery systolic pressure (PASP) and the presence and severity of tricuspid regurgitation (TR). On univariate analysis, Model of End-Stage Liver Disease (MELD) score, PASP, presence of ≥mild TR, post–operative renal replacement therapy (RRT) and spontaneous bacterial peritonitis were found to be significant predictors of adverse outcomes. On multivariate analysis, only ≥mild TR was found to predict both patient mortality (p = 0.0024, HR = 3.91, 95% CI: 1.62–9.44) and graft failure (p = 0.0010, HR = 3.70, 95% CI: 1.70–8.06). PASP and MELD correlated with post-LT intensive care unit length of stay (LOS) and, along with hemodialysis, were associated with hospital LOS and time on ventilator. In conclusion, pre-LT echocardiographic assessments of the right heart may be useful in predicting post-LT morbidity and mortality and guiding the selection of appropriate LT candidates.


American Society of Echocardiography


end-stage liver disease


fractional area change


intensive care unit


length of stay


liver transplantation


Model of End-Stage Liver Disease


mean pulmonary artery pressure


pulmonary vascular resistance


right atrial pressure


right heart catheterization


renal replacement therapy


right ventricle


right ventricular systolic pressure


tricuspid annular plane systolic excursion


tricuspid regurgitation


tricuspid regurgitation pressure gradient.


The survival of patients with end-stage liver disease (ESLD) after liver transplantation (LT) is highly dependent on cardiac function. A significant proportion of patients with ESLD have cardiac dysfunction, including high output cardiac failure, valvular heart disease and pulmonary venous/arterial hypertension, all of which affect peri-operative survival [1, 2]. Previous studies have shown that hemodynamic parameters from right heart catheterization (RHC), that is, mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR), are predictive of outcomes after LT [2, 3]. In these studies, MPAP ≥ 50 mmHg was associated with 100% mortality in the peri-operative period, whereas MPAP between 35–50 mmHg correlated with increased mortality in the subset of patients with PVR ≥ 250 dynes s/cm5. Most of the deaths in this cohort were cardiac in nature (right heart failure, ventricular arrhythmias), suggesting a higher rate of cardiac mortality in patients with unfavorable pre-LT hemodynamics [3]. While RHC provides useful predictive hemodynamic data, it is invasive, relies on single, “snap-shot” measurements, and does not provide an assessment of myocardial structure and function.

Two-dimensional (2D)/Doppler echocardiography has been widely used as a screening modality for estimating cardiac hemodynamics and the need for RHC [4, 5]. Echocardiography has become standard of care in the evaluation of patients undergoing LT and is helpful for excluding portopulmonary hypertension [5]. Despite its use as a screening modality for cardiac abnormalities, portopulmonary hypertension and the need for RHC, echocardiographic evaluation of the right heart has not yet been studied as an independent predictive tool for post–operative outcomes.

Therefore, we sought to determine whether echocardiographic indices of right heart structure and function were independently associated with morbidity and mortality post-LT. We hypothesized that abnormalities in right heart structure and function correlated with adverse outcomes post-LT.

Patients and Methods

Study sample

We retrospectively studied consecutive adult (age > 18 years) ESLD patients who underwent LT from 2007 to 2010. At our institution, all LT candidates routinely underwent screening echocardiography. Patients with evidence of right ventricular (RV) systolic dysfunction, septal flattening or severe TR on echo with moderate–severe portopulmonary hypertension (MPAP > 40 mmHg and PVR > 240 dynes s/cm5) on RHC that did not respond to vasodilator treatment were not considered candidates for LT at our center and not analyzed as we only included patients who underwent LT. In the LT population, patients with human immunodeficiency virus (HIV) (due to possible underlying HIV associated pulmonary hypertension), those with incomplete pre-LT echocardiographic images and patients undergoing re–transplantation were also excluded from analysis. Follow-up was achieved for at least 1 year in all surviving patients. Pretransplant demographic, clinical and laboratory data were collected for each patient. Data on post-LT outcomes, including patient and graft survival, causes of death, cardiovascular events, total hospital length of stay (LOS), intensive care unit (ICU) LOS, time on ventilator, need for post–operative renal replacement therapy (RRT) and infectious complications, were recorded from the electronic chart and transplant database. Presence of hepatic vascular compromise was evaluated for by reviewing post-LT day 1 liver ultrasounds. Patient survival was defined as the time from transplantation to death or last follow-up, and graft survival was defined as time from transplantation to death or re–transplantation. Patients were censored to time of death or date of last contact. This study was approved by the Northwestern University Institutional Review Board.


The pretransplant echocardiogram of each patient was analyzed by a single trained reader (L.K.) with oversight from a board certified cardiologist (S.J.S.), blinded to all other data, including outcomes. All right heart measurements were based on criteria outlined by the American Society of Echocardiography (ASE) guidelines for the evaluation of the RV [6] and valvular regurgitation [7]. In cases where patients underwent more than one pre-LT echocardiogram, the one closest to the time of transplantation was analyzed. Patients who underwent post-LT echocardiography were also identified, and their echocardiograms and clinical outcomes were analyzed using the same protocol outlined above. The full details of the standard protocol for echocardiographic assessment at our institution are available in the Supplementary Material.

Multiple echocardiographic measurements were recorded, with specific emphasis on right heart indices: pulmonary artery systolic pressure (PASP), presence and severity of tricuspid regurgitation (TR) and measurements of RV structure and function [6, 7]. The tricuspid regurgitation gradient (TRPG) was calculated from the peak TR velocity using the modified Bernoulli equation: TRPG (mmHg) = 4 V2, where V denotes the highest continuous wave Doppler measurement of the TR velocity (m/s) in the parasternal short axis (aortic level), RV inflow and apical 4-chamber views. The right ventricular systolic pressure (RVSP) was estimated by adding the right atrial pressure (RAP) to the TRPG. RAP was uniformly assigned as 10 mmHg, since it could not be estimated from the echocardiograms due to the lack of subcostal views, which precluded measurements of the inferior vena cava [8]. PASP was defined to be equal to RVSP in the absence of RV outflow obstruction or pulmonary valve stenosis. The presence and severity of TR (graded as none/trace, mild, moderate or severe) was qualitatively assessed by evaluating the size, direction and characteristics of the TR jet using Doppler color flow imaging as outlined by the guidelines [7]. Right ventricular diameter, size and area were measured at end diastole in the apical 4-chamber view. Fractional area change (FAC) was calculated in the standard manner [100 × (RV end diastolic area) − (RV end systolic area)/(RV end diastolic area)]. Tricuspid annular plane systolic excursion (TAPSE) was measured in the apical 4-chamber view, as described previously [9]. Finally, data on left heart structure and function, including left atrial dimension, left ventricular end diastolic dimension and septal wall thickness were also collected [6].

Statistical analysis

Prior to final statistical analysis, preliminary data were analyzed using univariate and graphical methods wherever applicable, to facilitate inspection and interpretation of the data. Outliers and influential observations were identified and checked for accuracy. All data were summarized using appropriate descriptive statistics (e.g. mean and standard deviation for continuous variables, count and frequency for categorical variables). Kaplan–Meier analysis was used to evaluate patient survival between the TR and non-TR groups using log-rank test.

Data were analyzed using both univariable and multivariable analysis. Linear regression was conducted for continuous outcomes (hospital LOS, ICU LOS and total time on ventilator) while logistic regression was used for binary outcomes (post-LT RRT and infection). Hazard ratios (HR) were calculated using Cox proportional hazards regression model for survival outcomes (patient and graft survival). Independent variables entered to the regression models predicting post-LT outcomes included patient age, MELD score at time of LT, pre-LT RRT, TR, RV FAC, TAPSE, RV/LV ratio, PASP, SBP, RV end-diastolic area, QT length, diastolic parameters (E/A ratio, deceleration time, isovolumetric relaxation time, size of LA, ejection fraction, wall motion thickness and ratio of pre–ejection period to LV ejection time) and donor variables (including age, cold ischemia time and donor type). Candidate covariates were assessed for inclusion into the multivariable model and were selected if p ≤ 0.15 in the univariate results. Throughout the report, confidence interval estimation was using Wald method and statistical significance was established at an alpha level of .05. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC).


Of the 291 patients receiving LT during the study period, 257 patients underwent pretransplant 2D/Doppler echocardiography with images available for review. From this subset, 7 HIV positive patients, 8 re-LT patients and 26 patients with incomplete Doppler images were excluded. A total of 216 patients met the inclusion and exclusion criteria and underwent echocardiography at a median 71 (IQR: 15–160) days prior to LT (Table 1). The mean age of the cohort was 55 ± 11 years and patients were predominantly male (62%). The majority of patients were white (72%), and the prevailing etiology of liver disease was hepatitis C (37%), followed by alcohol (30%), nonalcoholic steatohepatitis/cryptogenic (18%) and other (15%). The average MELD score at the time of transplantation was 25 ± 11 and the mean post-LT follow-up was 598 ± 330 days. No patients were lost to follow-up. Three patients were on therapy for portopulmonary hypertension with pulmonary vasodilators and showed improvement in their clinical and echocardiographic parameters, including PASP and TR prior to LT. At the time of LT, severity of TR in this group was ≤mild TR, and did not change post-LT. A summary of echocardiographic measurements can be found in Table 2.

Table 1. Patient characteristics
Patient characteristics (n = 216)
  1. LT, liver transplantation; MELD, Model of end-stage liver disease.
Age—years56 ± 11
Male sex—no. (%)133 (62)
Race—no. (%)
Caucasian155 (72)
African American11 (5)
Hispanic26 (12)
Asian9 (4)
Other/unknown15 (7)
Etiology of ESLD—no. (%)
Hepatitis C80 (37)
Alcohol66 (30)
NASH/cryptogenic38 (18)
Other32 (15)
Medical comorbidities—no. (%)
Coronary artery disease20 (9)
Hypertension67 (31)
Diabetes mellitus51 (24)
Chronic obstructive pulmonary disease11 (5)
Chronic kidney disease (non–hepatorenal syndrome)8 (4)
Pre-LT renal replacement therapy50 (23)
Complications of liver disease—no. (%)
Hepatic encephalopathy103 (48)
Ascites106 (49)
Spontaneous bacterial peritonitis34 (16)
Hepatorenal syndrome50 (23)
Esophageal varices102 (47)
Transjugular intrahepatic portosystemic shunt21 (10)
Hepatocellular carcinoma54 (25)
Labs at time of LT
International normalized ratio2.0 ± 1.2
Creatinine (mg/dL)1.8 ± 1.5
Total bilirubin (mg/dL)10.8 ± 12.9
Alanine aminotransferase (unit/dL)212 ± 816
Aspartate aminotransferase (unit/dL)311 ± 1284
Sodium (mEq/L)136 ± 5
MELD score at time of LT25 ± 11
Mean post-LT follow-up—days598 ± 330
Table 2. Echocardiographic measurements
Echocardiographic characteristicMean and standard deviation (except where noted differently)Reference standard per American Society of Echocardiography Guidelines
  1. LV, left ventricle; RV, right ventricle.
Septal wall thickness (cm)1.0 ± 0.20.6–1.0
Posterior wall thickness (cm)1.0 ± 0.20.6–1.0
LV end-diastolic dimension (cm)4.6 ± 0.73.9–5.9
LV end-systolic dimension (cm)2.7 ± 0.62.0–4.0
Left atrial dimension (cm)3.6 ± 0.72.7–4.0
LV mass index (g/m2)80.5 ± 20.944–88 (varies by male/female)
LV ejection fraction (%)63.3 ± 5.6>55
RV diameter, parasternal long-axis (cm)3.7 ± 0.6
RV diameter, parasternal short-axis (cm)3.6 ± 0.6
RV maximal diameter, apical 4-chamber view (cm)4.0 ± 0.72.4–4.2
RV end-diastolic area (cm2)23.7 ± 6.511–28
RV end-systolic area (cm2)14.8 ± 6.64–15
RV fractional area change0.4 ± 0.10.35–0.63
Tricuspid annular plane systolic excursion (cm)2.4 ± 0.81.6–3.0
RV/LV maximal diameter ratio (measures RV dilatation)0.8 ± 0.1<0.6 normal; 0.7–0.9 moderate; >1 severe
Tricuspid regurgitation (presence, severity)—no. (%)
None123 (56.9)
Mild75 (34.7)
Mild–moderate7 (3.2)
Moderate6 (2.8)
Moderate–severe5 (2.3)
Pulmonary artery systolic pressure (mmHg)38.21 ± 11.57
Stroke volume (mL)84.98 ± 26.42
Cardiac output (L/min/m2)9.76 ± 2.43

On univariate analysis, PASP, severity of TR (≥mild TR), pre-LT RRT, pre-LT SBP and MELD score at LT was found to be significantly associated with adverse outcomes, for example patient and graft survival, ICU LOS, total LOS, time on ventilator, need for post-LT RRT and post–operative infection (tables in Supplementary Section). Other measures of right ventricular structure and function, including RV FAC, TAPSE and RV/LV ratio, were not statistically significant on univariate analysis.

Of the variables that were significant (p ≤ 0.15) on univariate analysis, only severity of TR was associated with both patient and graft survival on multivariate analysis (Table 3). This relationship is further demonstrated in the Kaplan–Meier curves (Figures 1 and 2) for patient and graft survival according to the severity of TR (p = 0.002 and p < 0.001, respectively). Regarding predictors of other post-LT short-term outcomes (Table 4), MELD at LT, pre-LT RRT and pre-LT PASP on echocardiography were associated with total LOS, time on ventilator and the need for post-LT RRT. MELD and PASP were additionally associated with ICU LOS and MELD alone with post-LT infection. Neither severity of TR nor history of SBP was predictive of these short-term outcomes.

Table 3. Multivariate predictors of patient and graft survival
Pre-LT variablePatient survivalGraft survival
Hazard ratio95% Confidence intervalp-ValueHazard ratio95% Confidence Intervalp-Value
  1. Pulmonary artery systolic pressure and spontaneous bacterial peritonitis were not significant on univariate analysis so these were excluded from the multivariate model.
MELD score at time of LT1.040.97––1.070.18
Pre-LT RRT1.270.46–3.510.641.470.58–3.720.42
Severity of TR (≥mild TR)3.911.62–9.440.0023.701.70–8.060.001
Figure 1.

Patient survival following liver transplantation based on the presence or absence of ≥mild tricuspid regurgitation (log rank test, p = 0.0018), where 0 = none or trace TR and 1 = mild, moderate or severe TR.

Figure 2.

Graft survival following liver transplantation based on the presence or absence of ≥mild tricuspid regurgitation (log rank test, p = 0.0006), where 0 = none or trace TR and 1 = mild, moderate or severe TR.

Table 4. Multivariate predictors of short-term post-LT outcomes
Pre-LT variableICU stay (days)LOS (days)Ventilator time (days)Post-LT RRTInfection
CESEp-ValueCESEp-ValueCESEp-ValueOR95% CIp-valueOR95% CIp-value
  1. PASP, pulmonary artery systolic pressure; SBP, spontaneous bacterial peritonitis; LOS, length of stay; CE, co–efficient estimate; SE, standard error; OR, odds ratio; —, not significant on univariate analysis.
MELD score at time of LT0.220.080.0050.390.10<0.0010.170.060.0041.091.04–1.15<0.0011.071.02–1.130.01
Pre-LT RRT3.541.950.075.132.520.044.751.540.0025.882.33–14.29<0.0011.570.55–4.440.40
Severity of TR (≥mild TR)1.091.420.45

Analysis of RV end diastolic area as an additional covariate in the multivariate models did not change any of the associations. Severity of TR remained independently associated with death (p = 0.002) and graft failure (p = 0.001). Furthermore, entering donor characteristics, including donor age, cold ischemia and donor type (i.e. donation after cardiac death) in the multivariate model did not change any of the associations either. Severity of TR remained independently associated with death (p = 0.002) and graft failure (p = 0.001). Finally, analysis of LV systolic and diastolic parameters by TR group (TR none/trace vs. TR mild or greater) showed no significant differences (see table in Supplementary Section).

Overall patient survival at 30 days was 97.7%, at 6 months 93.5%, at 1 year 90.3% and at last follow-up 88.4%. Of the patients that died (N = 25), the predominant cause of death was sepsis (Table 5). Cardiovascular deaths accounted for 20% of deaths, most of which were beyond the 30-day postoperative period. Patients with ≥mild TR accounted for 71% of graft failures and 58% of deaths. The predominant causes of death in the cohort with ≥mild TR was unknown (33%, N = 6) followed by cardiovascular (28%, N = 5) and sepsis (22%, N = 4).

Table 5. Survival data and cause of death
CharacteristicN = 216
Graft survival at 1 year—no. (%)185 (86)
Overall patient survival—no. (%)
At 3 months211 (98)
At 6 months202 (94)
At 1 year195 (90)
Primary cause of death in all patients—no. (%)N = 25
Sepsis10 (40)
Cardiovascular5 (20)
Unknown6 (24)
Respiratory3 (12)
Other1 (4)
Primary cause of death in patients with ≥mild TR—no. (%)N = 18
Unknown6 (33)
Cardiovascular5 (28)
Sepsis4 (22)
Renal2 (11)
Other1 (5)
Timing of patient deaths with ≥mild TR—no. dead (%)N = 18
At 1 month5 (28)
At 3 months3 (17)
At 6 months2 (11)
At 1 year4 (22)
>1 year4 (22)
Primary cause of Re-LT in all patients—no. (%)N = 6
Hepatic artery thrombosis and/or ischemic cholangiopathy5 (67)
Primary nonfunction1 (17)

Thirty-one patients had post-LT echocardiograms at a median 8 (IQR: 2–105) days from LT. Seventy-four percent (23/31) had graft failure and echocardiography performed to assess cardiac function post-LT or prior to considering re–transplantation. When comparing pre- and post-LT echocardiograms in this small subset, the severity of TR was the same in 69.6% of patients, worse in 21.7% of patients and improved in 8.7%.

All transplanted patients underwent a liver ultrasound with Doppler flow on postoperative day 1 to assess the liver graft. No evidence of hepatic vascular compromise (i.e. reversal of flow in the hepatic/portal veins or inferior vena cava) was noted in the subset of patients with ≥mild TR.


Echocardiography has long been validated as a screening modality for left ventricular dysfunction and pulmonary hypertension in patients undergoing LT [5, 10, 11]. Our data suggest that beyond its utility as a screening tool for left ventricular dysfunction and pulmonary hypertension, pretransplant echocardiographic evaluation of the right heart can be useful in detecting patients at higher risk for significant post-LT outcomes. Specifically, on multivariate analysis, the severity of TR on pre-LT echocardiography was independently predictive of graft and patient survival. In addition, PASP estimation on echocardiography prior to LT was associated with peri-operative outcomes (total and ICU LOS, ventilator time, need for post-LT RRT), as well as other known predictors such as MELD and pre-LT RRT.

Our results have potential implications for transplant candidates and recipients. The severity of TR correlated with 1-year patient and graft survival, which are major initial benchmarks for success with LT. The assessment of right heart structure/function and TR severity is not obtainable from pre-LT RHC, which currently serves as the gold standard in the evaluation of pre-LT cardiac hemodynamics. Our findings suggest that evaluation of severity of TR and PASP may be important in identifying LT recipients at highest risk for complications and should be considered in concert with data obtained from RHC.

The correlation between TR severity and post-LT survival is a novel finding. Only one prior report found a cut-off TR jet velocity of 3.0 m/s was associated with 1-year post-LT survival [10]. However, this study only analyzed TR jet velocity and did not analyze TR severity and other right heart parameters based on ASE guidelines [7]. This finding begs the question as to why TR has such an impact on post-LT graft and patient survival. The pathogenesis may be speculatively related to the backpressure exerted by prolonged TR, leading to eventual hepatic congestion, graft failure and other long-term complications. Alternatively, TR may be a marker of poor reserve or perfusion, highlighted when patients have clinical deterioration (i.e. cardiovascular failure or sepsis). Interestingly, evaluation of post-LT echocardiograms showed that the severity of TR remained similar post-LT in the majority of patients with graft failure, although this was a select group who had this performed post-LT for different reasons and not by protocol. Prospective studies of patients with pre-LT TR are needed to monitor the progression or severity of TR post–operatively, and further studies are needed to determine if the impact of TR pre-LT can be minimized to improve outcomes.

In non–hepatic transplant recipients and non–transplant surgical/medical patients, limited data exist regarding an independent association between TR and morbidity and mortality. The liver graft may be more susceptible to right heart dysfunction than in other medical and surgical settings, given the high requirement for adequate hepatic in-flow and out-flow for optimal function. This is evidenced by the poor outcomes of patients with ESLD who have significant pulmonary hypertension, although deaths in this situation are mainly related to right heart, not allograft, failure [1-3]. In addition, the liver graft at risk for preservation injury, rejection, recurrent viral disease and other types of injury may be even more sensitive to diminished right ventricular function.

The association of pre-LT RRT, PASP on echocardiography and MELD score with adverse short-term postoperative outcomes has been reported previously [2, 3, 12-14]. Specifically, the presence of elevated PASP on echocardiography was shown to have an effect on short-term post-LT outcomes [2, 3]. In our study, however, patients with severe, untreated portopulmonary hypertension were excluded from transplantation and thus not analyzed in this post-LT outcome study. These patients typically fare poorly with transplantation, and in the same vein, our group with elevated PASP on echocardiography (albeit not too high to exclude transplantation) had more immediate complications, possibly as an indication of right heart volume and/or pressure overload in the peri-operative period [1, 2, 15]. An elevated creatinine, a significant component of the MELD score calculation and the need for RRT are well known as risk factors for requiring continued RRT and other associated short-term adverse outcomes [16, 17].

The study has some limitations as a retrospective analysis. Patients with severe right ventricular dysfunction, markedly elevated pulmonary pressures and severe TR on initial cardiac assessment were excluded from the analysis, as these patients were not deemed transplant candidates. Thus, only a small percentage of our study cohort (3.7%) had a subsequent RHC performed pre-LT to confirm intracardiac and pulmonary pressures. This precluded our ability to assess an association between echocardiographic and RHC indices (e.g. MPAP, PVR) as well as their independent or combined prediction of post-LT outcomes. Echocardiographic estimation of PASP, based on several assumptions, including the simplified Bernoulli equation and noninvasive estimation of RA pressure, could have attenuated the associations between PA pressure and outcomes examined in our study. Echocardiographic measurements and images were obtained by different sonographers but separately analyzed by a single trained reader for the purposes of this retrospective study. In a prospective study, a specified protocol with dedicated RV views could provide better images for data extraction, and RAP could be estimated rather than uniformly assigned to be 10 mmHg [8]. In addition, we only used a single time point (one echocardiogram) closest to the LT procedure to correlate with outcomes. Serial echocardiographic measures and, in particular, immediate pre- or intra-operative assessments might have even been more predictive of short- and long-term outcomes. Lack of liver biopsy data was another limitation, which would have allowed for assessment of congestive hepatopathy. Finally, only a small percentage of our patients underwent post-LT echocardiograms, as it was not in our protocol to monitor patients unless clinically indicated. Thus, it is unclear if poor outcomes were associated with post-LT progression of TR or other untested risk factors.

In conclusion, echocardiographic assessments of the right heart may be predictive of adverse post-LT outcomes and useful in the selection and monitoring of LT candidates and recipients. Such data could be used in adjunct to findings from RHC to further risk stratify patients prior to LT. Further prospective studies tied to hemodynamic assessments before and after LT are needed to validate our results.


The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.