Intraoperative TOE guided management of newly diagnosed severe tricuspid regurgitation and pulmonary hypertension during orthotopic liver transplantation: a case report demonstrating the importance of reversibility as a favorable prognostic factor
Tricuspid regurgitation (TR) and pulmonary hypertension (PHT) are highly dynamic cardiovascular lesions that may progress rapidly, particularly in the orthotopic liver transplantation (OLT) waitlist population. Severe TR and PHT are associated with poor outcomes in these patients, however it is rare for the two to be newly diagnosed intraoperatively at the time of OLT. Without preoperative information on pulmonary vascular and right heart function, the potential for reversibility of severe TR and PHT is unclear, making the decision to proceed to transplant fraught with difficulty.
We present a case of successful orthotopic liver transplantation (OLT) in a 48 year old female with severe (PHT) (mean pulmonary arterial pressure > 55 mmHg) and severe TR diagnosed post induction of anaesthesia. The degree of TR was associated with systemic venous pressures of > 100 mmHg resulting in massive haemorrhage during surgery and difficulty in distinguishing venous from arterial placement of vascular access devices. Intraoperative transoesophageal echocardiography (TOE) proved crucial in diagnosing functional TR due to tricuspid annular and right ventricular (RV) dilatation, and dynamically monitoring response to treatment. In response to positioning, judicious volatile anaesthesia administration, pulmonary vasodilator therapy and permissive hypovolemia during surgery we noted substantial improvement of the TR and pulmonary arterial pressures, confirming the reversibility of the TR and associated PHT.
TR and PHT are co-dependent, dynamic, load sensitive right heart conditions that are interdependent with chronic liver disease, and may progress rapidly in patients waitlisted for OLT. Use of intraoperative TOE and pulmonary artery catheterisation on the day of surgery will detect previously undiagnosed severe TR and PHT, enable rapid assessment of the cause and the potential for reversibility. These dynamic monitors permit real-time assessment of the response to interventions or events affecting right ventricular (RV) preload and afterload, providing critical information for prognosis and management. Furthermore, we suggest that TR and PHT should be specifically sought when waitlisted OLT patients present with hepatic decompensation.
KeywordsLiver transplantation Tricuspid regurgitation Pulmonary hypertension Central venous hypertension Pulmonary artery catheter Trans-oesophageal echocardiography, case report
Chronic Liver Disease
Central venous pressure
Left atrial pressure
Liver function tests
Left ventricle; Left ventricular
Left Ventricular Outflow obstruction
Minimum alveolar concentration
Mean arterial pressure
- MELD score
Model for End Stage Liver Disease score
Mean pulmonary arterial pressure
Orthotopic liver transplant
Pulmonary arterial pressure
Pulmonary capillary wedge pressure
Pulmonary vascular resistance
Right ventricle; right ventricular
Systolic pulmonary arterial pressure
Tricuspid annular plane systolic excursion
Tricuspid regurgitation (TR) shares a complex relationship with chronic liver disease (CLD). Commonly seen in association with Pulmonary hypertension (PHT), TR severity more than mild is independently associated with cholestatic derangements in ‘liver function tests’ (LFTs), and the strength of the association dependent on TR severity . The subsequent increase in central venous pressures reduces hepatic perfusion pressure, adding ischaemic stress to the liver and, increases venous bleeding during OLT. Liver disease itself may cause or worsen functional TR (i.e.TR without structural abnormality of the valve leaflets ) by increasing RV afterload or RV preload. This may be caused by an increased pulmonary vascular resistance due to porto-pulmonary hypertension (PoPH) or an increased pulmonary vascular blood volume due to a high cardiac output and/or fluid overload, often referred to as circulatory overload, or by impairing left ventricular function and increasing left atrial pressure (LAP) , due to cirrhotic cardiomyopathy. Other cause of pulmonary hypertension may also be present, such as pulmonary emboli, left ventricular failure and respiratory disease. The increase in RV preload also seen in liver disease worsens functional TR via an increase in systemic venous blood volume. Determining the cause is crucial for accurate prognostication and treatment. Severe PHT (defined as a mean PAP > 45 mmHg) associated with CLD is considered an absolute contraindication to transplantation in many centres worldwide . Thus aggressive management of PHT in these patients allows more to proceed to transplant.
The highly load dependent nature and potential rapid progression of functional TR increases the likelihood of patients presenting for OLT with new onset severe TR. International liver transplant waitlist guidelines variably recommend transthoracic echocardiography (TTE) from every 3 months to 12 months; however evidence supporting the efficacy of this timing for detection of severe TR prior to OLT is lacking. Due to the co-dependent nature of TR, PHT and CLD, precipitants of hepatic decompensation may acutely worsen TR, and significant TR can worsen hepatic function, resulting in a rapid deterioration of both right heart function and liver function. Thus it is important to exclude right heart lesions when an acute deterioration of liver function is noted.
When TR and/or PHT are identified in an OLT waitlisted patient, determining the cause and subsequently optimizing cardiac function, volume state, and PHT is associated with reduced postoperative mortality [4, 5]. In particular, pulmonary vasodilator therapy, initiated pre-operatively, has been successfully used to lower PAP and to improve outcomes in some patients [4, 5, 6]. When diagnosed incidentally on the operating table however, opportunity for comprehensive assessment and establishment of reversibility is limited. We present a case of severe TR and PHT diagnosed after induction of anaesthesia for OLT, with successful management demonstrating reversibility of both TR and PHT and subsequent good postoperative outcome.
Informed consent was obtained from the patient for the presentation of this case report with associated figures. A 48 year-old female patient, was scheduled for urgent OLT after an acute on chronic deterioration in hepatic function on a background of Caroli’s disease, non-alcoholic steato-hepatitis (NASH) and possible haemochromatosis. She had a known history of portal hypertension with oesophageal varices, ascites, and encephalopathy. Her past medical history also included morbid obesity and mild congenital cognitive impairment.
Echocardiography performed 18 months prior to transplantation demonstrated normal left and right ventricular (RV) systolic function and trivial TR. PAP was considered to be low but could not be estimated due to the minimal TR jet. Hence she did not receive a right heart catheterization study. At the time of waitlising her MELD (Model for End Stage Liver Disease) score was 16. However, her hepatic and renal function deteriorated in the six weeks prior to transplant, resulting in hospitalisation. This deterioration was triggered by an abdominal mesh infection. She was noted to have tender hepato-splenomegaly on admission. She was admitted to the intensive care unit (ICU) and placed on a terlipressin infusion twice during her admission; on both occasions however, her renal and hepatic function continued to deteriorate. Her surgery was therefore expedited. A repeat transthoracic echocardiogram was requested but not performed by the time of surgery; bedside TTE at time of surgery was considered but no trained staff were available to perform this test. Immediately prior to surgery her MELD score had risen to 39, with a bilirubin of 1062 micromol/L and a creatinine of 262 micromol/L.
Additional file 1: Movie Clip 1 (MP4 16544 kb)
The findings of severe TR, grossly elevated systemic venous pressures, severe PHT, and dilated RV were inconsistent with her prior TTE examination findings. Her severely elevated CVP and mPAP of > 45 mmHg raised serious concerns regarding hepatic perfusion pressure into the newly grafted liver, potentially uncontrollable venous bleeding intraoperatively, and the likelihood of a poor postoperative outcome after transplantation. With her SBP trending at 160 mmHg we considered inadequate anaesthesia as a potentially confounding factor to her PHT despite acceptable BIS values and thus went on to administer further isoflurane anaesthesia. Several interventions were instituted to assess the reversibility of the patient’s TR and PHT; reverse Trendellenberg positioning, hyperventilation to etCO2 to 30 mmHg, further increasing the isoflurane concentration and inhaled nitric oxide (NO). With these interventions mPAP fell to 40 and CVP to 31 however the TR remained severe; CI in fact improved to 3.5–4.5 at this time. On discussion with the surgical team the decision was made to proceed with transplantation with the knowledge that without transplantation the patient’s likelihood of survival was extremely low, and that the TOE findings of RV dilatation, raised LAP (LA end systolic diameter 4.5 cm [normal < 3.3 cm]; interatrial septum fixed to the right ), and absence of left heart disease, suggested a hypervolemic state as a significant but reversible contributor to the degree of TR.
Additional file 2: Movie Clip 2 (MP4 11645 kb)
The remainder of the operation proceeded uneventfully with ongoing mild TR and normal RV size and systolic function. Blood loss continued to be an issue but was managed with judicious volume replacement whilst monitoring for worsening of TR and RV dilatation on TOE. Total infused volume was 23 l, consisting of 6.4 L of autologous red cells, 2.3 L of packed red blood cells, 10 L of Plasmalyte-148 (Baxter International Inc., Deerfield IL), 1.7 L of 20% albumin, 5 units of fresh frozen plasma, 10 units of cryoprecipitate and 1 bag of pooled platelets.
The patient recovered well postoperatively with serum creatinine stabilising at 106 micromol/L and a formal post-operative TTE showing normal RV and LV size and systolic function, and no significant valvular dysfunction. The patient was discharged to rehabilitation on day 13 post-transplantation and was well at follow up 2 years later.
Discussion and conclusions
Role of intraoperative transoesophageal echocardiography in assessment and management of severe tricuspid regurgitation during liver transplantation
Exclude structural TR
• Normal appearance and motion of tricuspid valve leaflets and para-annular structures
Exclude severe functional tricuspid regurgitation
Colour flow doppler
• Jet area > 10 cm2
• Large proximal flow convergence
• Vena contracta width > 0.7 cm
• Systolic flow reversal in hepatic veins
• Dense TR signal with short deceleration time
• Tricuspid inflow E wave > 1 cm/s
• Effective Regurgitant Orifice Area > 0.4 cm2
• Regurgitant Volume > 45 ml
Assess RV systolic function
• RV fractional area change
• RV systolic myocardial velocity
Assess degree of RV and tricuspid annular dilatation
• RV End Diastolic Area
• RV End Diastolic diameter (basal, mid, apical)
• Tricuspid Annulus Diameter
Assist quantification of left heart disease driving PHT
• Estimate LAP (LA size, inter-atrial septum mobility, E/e’)
• Assess LV diastolic and systolic function
• Quantify severity of mitral regurgitation/ stenosis
Monitor improvement in the above indices in response to interventions reducing:
• RV preload (eg. systemic venous blood volume; positioning)
• RV afterload (eg. pulmonary vascular blood volume; pulmonary vascular resistance; interventions to improve LAP)
The failure to diagnose this patient’s severe TR and PHT during her waitlist period reflects the rapidly progressive nature of these conditions, their self-perpetuating effects, and the complex pathophysiological interplay between CLD and TR/ PHT. Indeed, this was highlighted in Saragai’s study where there was a large discrepancy between estimated PAP by PAC at operation and historical TTE PAP measurement . Additionally, clinical signs and sequelae of TR and PHT are non-specific and may be incorrectly attributed to worsening hepatic function. These sequelae include worsening LFTs, fluid overload, peripheral oedema and renal dysfunction. Had TTE been performed at the time of her initial deterioration, severe TR/ PHT could have been identified earlier and right heart catheterization would have been performed . Attempts at optimizing volume state and pulmonary vascular resistance may have resulted in improved right heart haemodynamics by the time of surgery. The role of early right heart catheterization cannot be overemphasized as it provides the most accurate estimation PVR and the potential for determining reversibility of PHT over time, possibly influencing the decision for earlier transplantation. Although terlipressin has a strong evidence base for improving renal perfusion in cirrhotic liver disease by constricting splanchnic beds and mobilizing blood to the systemic circulation, undesirable effects on PHT have been demonstrated . In retrospect, the deterioration in liver and kidney function in response to terlipressin as occurred twice in this case was indicative that the patient had TR and or significant volume overload and should have prompted further investigation.
With regards to the ideal timing of repeat TTE whilst on the waiting list, there is little evidence of the optimal timing and no priority given to specifically excluding TR/ PHT when apparent hepatic deterioration occurs. Although our institutional protocol suggests repeating a TTE every year, in our patient’s case, her remote place of residence contributed to her loss to follow up for repeat TTE. We propose that any patients waitlisted for OLT who are admitted with a decompensation of their CLD, or require terlipressin therapy, have TTE performed to screen for new or worsening TR/ PHT that may be a contributing and/ or compounding factor to hepatic decompensation.
When pulmonary hypertension is diagnosed in patients with cirrhosis, it is important to distinguish whether the cause is due to circulatory overload or from POPH, as the treatments and prognoses are different. Right heart catheterization with measurement of PVR and pulmonary capillary wedge pressure (PCWP) has been recommended , but this was not helpful in our case as we could not wedge the PAC. The inability to wedge a PAC has been reported to occur in up to 12% of cases , and in this case was most likely due to a hypervolemic pulmonary circulation causing dilatation of the pulmonary arterial tree to a wider dimension than that of the PAC balloon. Other causes of PHT, including pulmonary emboli, severe respiratory disease and left ventricular failure, should also be considered.
In patients awaiting OLT with significant PHT, a trial of systemic or pulmonary vasodilator therapy can help in the decision-making process to distinguish responders from non-responders [8, 17]. Inhaled NO alone did not provide reassurance in our case. However, increasing pulmonary vasodilation with increased isoflurane administration, reverse Trendellenberg positioning and carefully monitored permissive surgical hypovolemia caused the PHT and TR to improve (Fig. 4). The reversibility in PHT with these manoeuvres suggested that the cause of the PHT in our patient was circulatory overload, which confers a better prognosis. Koh and colleagues  achieved a similar result by emergently draining 9 l of ascites from the patient in their case report of acutely reversible PHT. Park and colleagues have shown that PHT that resolves during transplantation confers a prognosis similar to patients without PHT . Other means of demonstrating reversibility by reducing venous return in the acute preoperative period could have also been achieved with a trial of diuretics or haemofiltration. The remarkable intra-operative resolution of the TR, from severe to mild, coupled with a concomitant reduction in RV size, suggests that the TR was at least partially attributable to RV dilatation.
In conclusion, we have demonstrated that use of intraoperative TOE in addition to other invasive monitors can successfully guide the acute diagnosis, on-table management and demonstration of reversibility of unexpected severe TR and PHT just prior to orthotopic liver transplantation. This assisted the ultimate decision to proceed with transplant and achieved successful transplantation with a good postoperative patient outcome. Nevertheless, every effort should be made to detect new onset severe TR and PHT in OLT waitlisted patients by performing regular TTE screening and having a high index of suspicion of TR and PHT at times of hepatic decompensation.
BP Major contribution to writing of Manuscript, Patient Consent. RH Major contribution to writing of Manuscript. FD Interpretation and selection of Echocardiography images, Literature review, Manuscript editing. DB Extraction of data including images, Manuscript editing and formatting, Ethics Submission. RJ Manuscript editing. CT Major contribution to Manuscript Revision including figures, tables. All authors read and approved the final manuscript.
This case report was unfunded.
Ethics approval and consent to participate
The patient was consented for the procedure undertaken in line with hospital policy. Ethics approval was obtained for publication (see Consent for Publication below).
Consent for publication
After reviewing the manuscript, written informed consent for publication was obtained from the patient. The manuscript and the patient’s signed consent form have been reviewed by a member of the ethics committee at Austin Health and approved for publication. Austin Health have also given consent for publication.
The authors declare that they have no competing interests.
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