Caval Valve Implantation for Tricuspid Regurgitation: Insights From the United States Caval Valve Registry

Abstract: Background. We sought to describe the outcomes of patients who underwent caval valve implantation (CAVI) for treatment of severe tricuspid regurgitation (TR) in the United States. Previous studies on CAVI have used a variety of techniques and transcatheter valves. We present our findings from CAVI with inferior vena cava (IVC) implant only using a single valve. Methods. Patients who were determined to be poor candidates for tricuspid valve surgery and underwent CAVI in the United States from March 1, 2013 through March 1, 2018 were included in this study. Data during hospitalizations and interim outpatient follow-up from each individual site were collected and entered into a central password-protected database. Results. A total of 24 patients were treated. The median age was 79.5 years, 63% were women, and 96% were white. Twenty-three of 24 patients underwent valve implantation with a 29 mm Sapien 3 valve (Edwards Lifesciences). There was a 100% rate of successful valve implantation. There were no cases requiring emergency surgery. Thirty-day mortality rate was 25%. The median survival as of last follow-up of all patients was 350 days. Pre- and postprocedure New York Heart Association (NYHA) class data were available in 11 of 24 patients; of these 11 patients, 72.7% improved at least 1 NYHA class from baseline. Conclusion. CAVI may be performed safely in a high surgical risk population with severe tricuspid regurgitation. Dedicated studies with longer-term follow-up are needed.  

J INVASIVE CARDIOL 2020;32(12):470-475. Epub 2020 October 22.

Key words: caval valve implantation, transcatheter aortic valve, tricuspid regurgitation, tricuspid valve surgery

Despite increased awareness of the morbidity and mortality associated with untreated severe tricuspid regurgitation (TR), rates of surgical correction remain low.¹ It is against this backdrop that the field of percutaneous therapy for severe TR has flourished, with multiple devices in early feasibility trials.² Many of these technologies rely on direct leaflet repair, annular reduction to restore normal coaptation, or alternative means of restoring coaptation.² An alternative to these strategies is caval valve implantation (CAVI). First described in 2010,³ the concept of CAVI is to place a valve outside of the heart heterotopically in the inferior vena cava (IVC), or in both the superior vena cava (SVC) and IVC, to ameliorate downstream effects of chronic right heart congestion. Previous data on CAVI have demonstrated an improvement in New York Heart Association (NYHA) functional class.^4,5 However, the data are heterogeneous due to the variety of transcatheter valves used for CAVI and the implantation techniques (ie, IVC vs IVC and SVC). We present our experience with CAVI using IVC implantation from the United States (US) Caval Valve registry.

Methods

The US Caval Valve registry was a retrospective study of patients who underwent CAVI from April 1, 2013 to March 31, 2018 at 7 participating centers in the United States. Eligible patients were determined to have symptomatic TR and to be poor candidates for surgical tricuspid valve intervention per local heart team discretion. All patients underwent anatomic screening to assess suitability for CAVI, most of which was by contrast computed tomography (CT). Patients were excluded if it was felt that IVC diameter at the superior-most hepatic vein greatly exceeded the diameter of the largest Sapien 3 valve size (29 mm; Edwards Lifesciences). Follow-up was obtained at time of hospital discharge and through routine outpatient clinic follow-up. Data were collected by each individual site and entered into a password-protected database for statistical analysis. Events were defined according to Valve Academic Research Consortium (VARC)-2 definitions. A waiver of informed consent was obtained.

The procedural steps have previously been described.⁶ Briefly, the procedure was performed via the femoral venous approach. A wire was externalized through the right internal jugular vein to serve as a rail. As the IVC normally is not calcified, prestenting of the IVC was performed using a Z stent (Cook Medical). The Z stent was also advanced through the femoral vein to provide scaffolding for implantation of the Sapien 3 valve. After satisfactory stent deployment, the valve was advanced through the Z stent and deployed so the skirt of the valve was placed just above the superior-most hepatic vein with the goal of creating a seal to prevent reflux of blood distal to the valve (Figure 1). 

Data were expressed as frequencies and percentages for categorical variables and median (range) for continuous variables. Overall survival was analyzed using the product-limit method with the Kaplan-Meier survival curve presented. Comparisons of interest between 2 groups by survivorship were implemented using the Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables. Multiple comparison adjustments were not made due to the exploratory nature of the study. P-values <.05 were considered statistically significant. SAS software, version 9.4 (SAS Institute) was used for all data analyses.

Results

A total of 24 patients underwent CAVI. Baseline characteristics are listed in Table 1. The median patient age was 79.5 years (range, 49.0-91.0 years). There was a high rate of pre-existing atrial fibrillation (79.2%) and nearly half of all patients had a history of pacemaker implantation (45.8%). In addition, 83.3% of patients had a history of chronic kidney disease (CKD). The majority of patients had at least moderate TR, and right ventricular (RV) function as measured by tricuspid annular plane systolic excursion was low to normal, at a median of 1.8 cm (range, 1.0-5.9 cm). IVC and hepatic vein CT dimensions are listed in Table 1. The median diameter of the IVC at the superior-most hepatic vein was 29.0 mm (range, 21.0-35.0 mm) and the distance from the superior-most hepatic vein to the right atrial/IVC junction was 29.0 mm (range, 4.9-98.0 mm).

Procedural characteristics are listed in Table 2. The majority of patients (95.9%) were in NYHA functional class III or IV prior to implantation. Most patients (87.5%) underwent implantation electively. All but 1 patient (who underwent implantation with a 23 mm valve) were implanted with a 29 mm valve. A valve was successfully deployed in 100% of the cases and no procedures were complicated by the need for emergency surgery. 

In-hospital characteristics are listed in Table 2. In-hospital mortality (defined as death in the hospital after the procedure) and 30-day mortality rates were 20.8% and 25.0%, respectively. Of the 5 patients who did not survive in the hospital, 1 death was deemed procedure related (defined as directly caused by the procedure in the opinion of the site review), as the patient developed worsening renal failure post CAVI and elected to pursue hospice care. There was 1 vascular complication (4.2%). Eighteen patients had follow-up echocardiograms to evaluate paravalvular or valvular regurgitation during admission. Of these, almost 90% had no evidence of leak. The vast majority of patients (87.0%) were on loop diuretics at discharge. A total of 11 patients had NYHA class assessments at both baseline and at a mean follow-up of 30.5 days (range, 14.0-64.0 days) (Figure 2). Of these 11 patients, 72.7% had improvement in NYHA class of at least 1 grade at follow-up compared with baseline, with only 1 patient (9.1%) considered worse at follow-up. 

Overall mortality occurred in 14 of 24 patients (58.3%) during a median total follow-up of 332 days (range, 2-1161 days) since implantation. The Kaplan-Meier survival curve is shown in Figure 3. Many of the deaths occurred in the first 3 months post valve implantation. The median survival for all patients through the end of study follow-up was 350 days (range, 2-1161 days). 

Discussion

To our knowledge, the current study is the largest experience of CAVI in the IVC using the Sapien 3 valve. Procedural success with CAVI was 100%, including both successful deployment of the valve and removal of the delivery system. However, it is important to note that valve embolization remains a potential complication of this procedure. In the TRICAVAL study,⁷ which was a randomized trial of CAVI vs medical therapy, there were 4 delayed complications (2 cases of stent migration and 2 cases of valve embolization). This highlights the challenges of fixing a transcatheter valve in the venous circulation. 

A hallmark of untreated TR is right-sided venous congestion, which may lead to renal and hepatic dysfunction.^8,9 Previous studies of the MitraClip device (Abbott Vascular) for tricuspid valve disease have demonstrated improvements in liver function, but not kidney function, in patients presenting with symptomatic severe TR.¹⁰ In CAVI, the flow from untreated TR is redirected away from the renal and hepatic veins. The ability to eliminate regurgitant flow into the IVC and hepatic vein is essential, and those patients without higher right atrial pressures are unlikely to derive significant benefit.

Rates of valvular regurgitation were low in our study, as the median diameter of the IVC at the superior hepatic vein was 29 mm. IVC size remains a major limiting factor at our center, precluding almost two-thirds of patients being evaluated in the HOVER trial (NCT02339974). Dedicated platforms are needed to address this issue.

Although the procedural mortality rate was 0%, the in-hospital mortality rate for our registry was 20.8%. This rate is similar to other early feasibility studies of heterotopic valve placement of both CAVI (16%) and valve in mitral annular calcification (MAC).^5,11 There exists a population of patients who are unlikely to see measurable benefit from CAVI, which raises the question of futility. Patient risk factors have been identified that may increase the mortality post transcatheter aortic valve replacement.¹² Similar risk factors will need to be identified for patients with severe TR to determine who will benefit from percutaneous therapies.

The rate of acute renal failure in this study was 20.8%. This is not surprising, as 80% of patients had a pre-existing diagnosis of chronic kidney disease and severe TR is a known risk factor for renal dysfunction.⁸ Currently, some contrast is necessary during CAVI to visualize anatomic landmarks, and contrast-sparing techniques are needed.

Many elderly patients with structural heart disease have underlying cardiac conduction disease, which may necessitate placement of a transvalvular tricuspid lead. The current experience with edge-to-edge repair suggests that tricuspid valve repair is feasible in patients with transvalvular leads.¹³ Pacemaker lead entrapment on the tricuspid valve, particularly the septal leaflet, can limit the effectiveness of this therapeutic option in cases of severe TR. CAVI may be a reasonable alternative in these patients.¹⁴

The association between TR reduction and symptom improvement in transcatheter valve therapy remains unclear. At 6-month follow-up in the Triluminate trial,¹⁵ the majority of patients experienced improvements in NYHA classification despite a residual rate of 42% with severe TR or greater. In the current registry, despite a 66% rate of severe TR or greater, 73% of patients experienced improvement in NYHA classification. The mechanism behind this improvement may be the prevention of venous backflow into the caval veins, allowing for more effective diuresis and relieving right heart congestion. This concept is illustrated from a CAVI implantation in a patient implanted outside of the registry (Figure 1) showing a reduction of the v-wave in the IVC immediately post implantation. 

Study limitations. This was a retrospective, observational study and our findings have several limitations. Events were adjudicated at each individual site rather than centrally. There was also no central core lab for echocardiographic interpretation. Follow-up data were not available in several patients (~50%) following hospital discharge post implantation at 30 days (eg, for NYHA). There was also a potential survival bias present, as one-quarter of the study subjects did not have follow-up data beyond hospital inpatient stay.

Conclusion

Our registry represents the initial human experience with CAVI in the United States. There was a high rate of successful valve implantation. Rates of paravalvular regurgitation were low, and selected patients experienced improvements in NYHA classification. Future studies of the effects on the right ventricle are needed, as are dedicated devices to allow a larger population of patients to be treated.

Acknowledgments. The first author would like to thank Carol O’Neill for her encouragement and dedication to the completion of this registry. 

From the ¹Henry Ford Center for Structural Heart Disease, Detroit, Michigan; ²Vanderbilt University Medical Center, Nashville, Tennessee; ³Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania; ⁴Rochester General Hospital, Rochester, New York; ⁵University of Washington Medical Center, Seattle, Washington; ⁶Community Health Network, Indianapolis, Indiana; ⁷University of California San Francisco, San Francisco, California; ⁸Massachusetts General Hospital, Boston, Massachusetts; and ⁹Willis Knighton Health System, Shreveport, Louisiana.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Depta reports consulting income from Edwards Lifesciences, Boston Scientific, WL Gore, and V. Wace Ltd. Dr McCabe reports personal fees from Edwards Lifesciences. Dr Wang reports personal fees from Edwards Lifesciences, Boston Scientific, and Materialise; grant support from Boston Scientific. The remaining authors report no conflicts of interest regarding the content herein.

The authors report that patient consent was provided for publication of the images used herein.

Manuscript accepted June 26, 2020.

Address for correspondence: Brian O’Neill, MD, Henry Ford Hospital, Clara Ford Pavilion #440, 2799 W. Grand Blvd, Detroit, MI 48202. Email: boneil3@hfhs.org

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