Transcatheter Tricuspid Valve Replacement and Liver Transplantation for Severe Tricuspid Regurgitation and Cirrhosis

Abstract

Background

The incidence of patients with cirrhosis and concurrent valvular heart disease is increasing. Moderate to severe tricuspid regurgitation (TR) is associated with increased mortality after liver transplantation (LT). Open cardiac surgery is recommended for patients with symptomatic severe TR, however LT candidates often face prohibitive surgical risk.

Case Summary

A 45-year-old woman with advanced cirrhosis awaiting LT was diagnosed with severe functional TR due to anatomical tricuspid valve incompetence (TVI). The tricuspid valve anatomy was unsuitable for transcatheter tricuspid edge-to-edge repair, a technique previously described in cirrhotic patients before LT. The patient underwent a transcatheter tricuspid valve replacement (TTVR) followed by LT.

Discussion

LT recipients with TR secondary to anatomical TVI have significantly lower 1-year survival. Minimally invasive valve interventions are promising alternatives for patients who are not cardiac surgical candidates, such as LT recipients with advanced cirrhosis.

Take-Home Message

Transcatheter tricuspid valve replacement may facilitate LT in high-risk candidates with severe TR due to TVI.

Visual Summary

The incidence of patients presenting for liver transplantation (LT) with concurrent severe valvular heart disease is increasing, posing complex challenges in clinical management.¹ Although severe valvular heart disease is often a contraindication to LT, advanced cirrhosis can preclude patients from undergoing open cardiac surgery. We describe a 45-year-old woman with end-stage liver disease (ESLD) awaiting LT who was admitted with severe functional tricuspid regurgitation (TR). The patient's tricuspid valve (TV) anatomy was unsuitable for transcatheter tricuspid edge-to-edge repair (TV-TEER), a technique previously used in patients with ESLD before liver transplantation.² To our knowledge, this is the first reported case of transcatheter tricuspid valve replacement (TTVR) used as a bridge to liver transplantation in a patient with cirrhosis and severe functional TR.

Take-Home Message

• •Transcatheter tricuspid valve replacement offers a minimally invasive strategy for the perioperative management of high-risk liver transplant candidates with severe symptomatic TR due to anatomic TVI.

History of Presentation

A 45-year-old woman was admitted with decompensated cirrhosis due to metabolic dysfunction–associated steatotic liver disease and increased alcohol intake. She presented with anasarca and acute-on-chronic renal failure. At admission, her sodium model for ESLD score was 31 (Table 1). During her hospitalization, she developed renal failure requiring dialysis, new-onset atrial fibrillation, and a methicillin-susceptible Staphylococcus aureus central line–associated bloodstream infection. Transthoracic echocardiography performed during assessment for LT demonstrated normal biventricular systolic function but severe TR due to tricuspid annular dilatation and valvular malcoaptation. She was symptomatic from severe TR with diffuse anasarca, ascites, lower extremity edema, and new-onset atrial fibrillation.

Table 1.

Patient Laboratory Test Values Relative to Transcatheter Tricuspid Valve Replacement and Liver Transplant

	Pre-LT		Post-LT
	6 wk Pre-LT and 5 wk Pre-TTVR	4 d Pre-LT and 5 d Post-TTVR	2 wk Post LT	6 mo Post LT
Hb (g/L)	76	71	86	103
INR	1.8	1.6	1.0	0.9
Platelets (×109/L)	48	22	150	254
Albumin (g/L)	36	33	24	33
Bilirubin (μmol/L)	48	41	10	6
ALT (U/L)	<9	<9	40	<9
AST	26	n/a	22	<8
ALP	108	233	108	134
GGT	52	86	39	40
Creatinine (μmol/L)	370	165	85	560

Bold text indicates laboratory values during the post–liver transplantation period.

ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyl transferase; Hb = hemoglobin; INR = international normalized ratio; LT = liver transplantation; n/a = not available; OLTx = orthotopic liver transplantation; TTVR = transcatheter tricuspid valve replacement.

Past Medical History

The patient's medical history was significant for metabolic dysfunction–associated steatotic liver disease and increased alcohol intake, obesity, and chronic renal failure.

Investigations

Right and left heart catheterization revealed a mean pulmonary artery pressure of 19 mm Hg, mean right atrial pressure of 30 mm Hg, pulmonary artery systolic pressure of 27 mm Hg, and pulmonary artery diastolic pressure of 15 mm Hg. The pulmonary vascular resistance was 0.47 WU, with a pulmonary capillary wedge pressure of 13 mm Hg and a left ventricular end-diastolic pressure of 16 mm Hg. Cardiac output and cardiac index by the Fick method were 10.6 L/min and 5.05 L/min/m², respectively.

Differential Diagnosis

Transesophageal echocardiography (TEE) was negative for vegetations, intracardiac shunts, and left-sided valvular disease. There was no evidence of coronary artery disease or pulmonary hypertension. The patient was diagnosed with severe functional TR secondary to annular dilation and volume overload. She underwent aggressive volume removal with continuous renal replacement therapy, resulting in a 40-kg reduction in total body weight. Despite significant volume removal, repeat transthoracic and transesophageal echocardiography continued to demonstrate severe TR due to anatomical tricuspid valve incompetence (TVI) and a large coaptation gap (Figure 1).

Figure 1.

Transesophageal Echocardiography Showing Severe Tricuspid Regurgitation

Severe tricuspid regurgitation due to tricuspid annular dilation and malcoaptation in a liver transplant candidate, visualized using transesophageal echocardiography after intravascular volume optimization. (A) Severe tricuspid regurgitation demonstrated with color-flow Doppler. (B) Large tricuspid valve coaptation gap with an incidental Chiari network observed in the right atrium.

Management

A multidisciplinary discussion involving hepatology, interventional cardiology, cardiac surgery, critical care, and anesthesiology was held. There was concern that proceeding with LT without TV intervention could precipitate postoperative congestive hepatopathy and allograft dysfunction. Given her advanced cirrhosis, the patient was not a candidate for isolated open surgical TV repair or replacement. Combined open surgical TV repair with LT was not feasible given our center's lack of experience with combined procedures. Although TV-TEER has been used in the setting of severe TR previously to facilitate LT,⁴ TTVR was felt to be a better option than TV-TEER given the size of the coaptation gap and the need to eliminate TR. Furthermore, if TV-TEER failed, there would be limited rescue options given the lack of candidacy for open cardiac surgical intervention. Given the patient's right ventricle (RV) systolic function was preserved, the RV was likely to tolerate transcatheter TV intervention without precipitating right heart failure. Thus, the multidisciplinary team decided to proceed with TTVR before LT.

The safety of TEE, an integral component to TTVR deployment, was evaluated before TTVR. Patients with ESLD may have contraindications to TEE including esophageal or gastric varices and active upper gastrointestinal bleeding. Two weeks earlier, the patient had undergone upper gastroduodenal endoscopy, where an actively bleeding gastric Dieulafoy lesion was clipped and moderate portal hypertensive gastropathy was noted. Although portal hypertensive gastropathy is not a contraindication to TEE, recent gastrointestinal bleeding is considered a relative contraindication. In LT recipients, the risk of upper gastrointestinal bleeding from TEE is low in patients with up to moderate gastric varices, although caution is advised in those with high-risk features such as previous esophageal rupture and variceal banding the day before LT.⁷ In this case, the benefit of TEE for guiding TTVR deployment was deemed to outweigh the risk, and probe manipulation was restricted to essential esophageal views to minimize risk.

The patient underwent transjugular TTVR with a bioprosthetic 60-mm LuX-Valve Plus (Jenscare Biotechnology) (Figure 2, Figure 3).⁸ The LuX-Valve Plus was selected, as the TV annular dimensions were too large for any other investigational TTVR. The LuX-Valve Plus requires insertion through the internal jugular vein and does not require transvenous pacing. At the time of this procedure, there were no approved TTVR devices available for commercial use. Therefore, this patient was treated under the Health Canada Special Access pathway of compassionate use.

Figure 2.

Transesophageal Echocardiography After Transcatheter Tricuspid Valve Replacement

Transesophageal echocardiography after transcatheter tricuspid valve replacement showing the tricuspid bioprosthetic LuX-Valve Plus in situ. (A) Bioprosthetic tricuspid valve deployed. (B) Right ventricle–focused midesophageal view with color-flow Doppler demonstrating no significant paravalvular or intravalvular regurgitation.

Figure 3.

Fluoroscopic Images of Transcatheter Tricuspid Valve Deployment

Fluoroscopic images (A) before, (B) during, and (C) after tricuspid valve deployment.

After the procedure, RV systolic function was normal, with moderate RV dilation, similar to baseline (RV diameter in apical 4-chamber view: 47 mm postprocedure vs 49 mm preprocedure). The valve demonstrated a mean gradient of 2 mm Hg at a heart rate of 83 beats/min. There was no transvalvular regurgitation and only trivial paravalvular leak (Figure 2).

Eight days after TTVR, the patient underwent successful orthotopic LT. Pathology of the liver explant demonstrated features consistent with burned-out steatohepatitis rather than congestive hepatopathy. The patient was extubated on postoperative day 3, transferred to the ward on postoperative day 6, and discharged to a community hospital 7 weeks after LT. She was discharged home 4 months after the LT.

Outcome and Follow-Up

One year after LT, the patient's liver allograft function remains normal, the TTVR continues to demonstrate a normal hemodynamic profile, and she remains in sinus rhythm. She is not under anticoagulation therapy, as she had 2 episodes of upper gastrointestinal bleeding perioperatively. The first episode, 2 weeks before TTVR, was due to an actively bleeding Dieulafoy lesion in the setting of moderate portal hypertensive gastropathy and was treated with clipping. The second, 17 days after LT, was attributed to mild residual portal hypertensive gastropathy; additional clips were applied to the Dieulafoy lesion owing to limited visualization during the procedure.

Discussion

Functional, or secondary, TR is the most common cause of TR and results from progressive tricuspid annular dilation with structurally normal valve leaflets. Primary cardiac disease can precipitate functional TR, leading to congestive hepatopathy and cirrhosis. Conversely, patients with cirrhosis may develop TR secondary to cirrhotic cardiomyopathy, pulmonary hypertension, or unrelated concurrent primary valvular disease. Severe TR is associated with significant mortality in the general population and in post-LT recipients.^2,9,10 Although open cardiac surgical intervention remains the standard of care for primary and secondary severe TR, transcatheter therapies are emerging as viable alternatives for patients deemed too high risk for open cardiac surgery.^1,3,6,8 These minimally invasive strategies may be advantageous in LT recipients who are considered too high risk for open cardiac surgery but have severe valvular heart disease that could contraindicate LT.¹¹

TTVR was shown to reduce markers of hepatic congestion in a large multicenter trial.⁶ Although TTVR improved symptoms and quality of life in the general population with severe symptomatic TR, only 11% of the study patients had liver disease, limiting the applicability of these findings for LT candidates.⁶ Emerging data suggest that LT recipients with severe TR secondary to anatomic TVI have significantly worse post-LT outcomes compared to those without anatomic TVI.⁵ It is physiologically plausible that addressing significant TR before LT may reduce post-transplant morbidity and mortality by decreasing hepatic congestion. However, evidence is lacking regarding the optimal management of TR in LT candidates, including risk stratification, identifying those who may benefit from peri-LT tricuspid valve intervention, and whether severe TR should constitute a contraindication to LT. Recipients of LT with severe TR secondary to TVI may be a particular subgroup of patients who benefit from peri-LT transcatheter tricuspid valve intervention. The current case outlines the successful use of TTVR as a bridge to LT in a patient with cirrhosis and severe functional TR from TVI, highlighting an alternative strategy for this high-risk patient population.

This case report has several limitations. The patient's outcome without TV intervention before LT remains unknown, and her long-term prognosis remains uncertain, as she is only one year post-LT. The optimal timing of TV intervention relative to LT is unknown, and it is possible that post-LT valvular intervention may have produced a similar outcome. Although our center has no experience in combined LT and open cardiac procedures, this could have been an alternative management strategy. Finally, the data are limited on the long-term durability of TTVR. The multidisciplinary consensus was that, should the TTVR fail over time, improved liver allograft function might allow the patient to become a candidate for open surgical repair or transcatheter valve-in-valve implantation.

Conclusions

Significant valvular heart disease may be identified during the evaluation for LT of patients with cirrhosis. Although severe valvular heart disease is often a contraindication to LT, advanced cirrhosis prevents patients from undergoing open cardiac surgery. We describe a 45-year-old woman with ESLD who presented with severe symptomatic functional TR. A multidisciplinary approach enabled successful TTVR, and the patient subsequently underwent LT. Further research is needed to clarify patient selection, optimal timing of valve intervention, and post-transplant outcomes after TV intervention.

Visual Summary.

Case Report Summary

Na-MELD = sodium model for end-stage liver disease; TR = tricuspid regurgitation.

Funding Support and Author Disclosures

Dr Cheung has been a consultant for Jenscare Biotechnology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.