The tricuspid valve has historically received less attention compared to the valves on the left side of the heart. Tricuspid valve disease, however, is more common than previously thought, and if left untreated, it poses a significant risk of morbidity and mortality.

Tricuspid regurgitation (TR) is a condition that is both underdiagnosed and undertreated yet can cause substantial morbidity and impact quality of life. It can lead to right-sided heart failure (HF) and is often a marker of poor prognosis in patients with HF as well as other cardiac conditions.

Fortunately, recent advancements in diagnostic tools and treatment options have expanded the range of available treatments, leading to improved patient outcomes. In the past decade, and especially in the last two or three years, the tricuspid valve has shed its label as "the forgotten valve."

"Until recently, the story of the tricuspid valve was that patients with significant TR suffered for a long time but were undiagnosed until their disease was severe. Then there weren't really any treatment options because they were too high risk for surgery," says Rebecca T. Hahn, MD, FACC, an interventional imager and a top expert on the tricuspid valve.

"Now, we're starting to see patients earlier and we're diagnosing TR better. Plus, we have some noninvasive transcatheter options, so it's a whole new game," she adds. Hahn is director of interventional echocardiography at the Columbia Structural Heart and Valve Center, Columbia University Irving Medical Center in New York.

Tricuspid Valves 101

The tricuspid valve is the largest valve by area in the human heart and the most caudal. It would be reasonable to assume that a healthy tricuspid valve has three leaflets, but that would be true only about half the time. As first described by Hahn, et al., about 54% of tricuspid valves consist of the trileaflet configuration, while the rest have two, four or more leaflets.¹

TR is a more significant and prevalent clinical issue compared to tricuspid stenosis (TS), which is rare, almost always seen in the context of rheumatic heart disease, and as a result seldom seen in developed countries. When severe, TS can be addressed surgically, particularly in patients undergoing left-heart valve surgery.

As with other valvular heart diseases, TR increases with age. The prevalence is higher in women than men, perhaps as much as fourfold higher, but men are more frequently diagnosed with TR. The basis for the higher female prevalence is unclear but is thought to relate to the higher prevalence of heart failure with preserved ejection fraction (HFpEF) in women.

"The natural history studies have suggested that the prevalence of TR is under 1%. But now that we're getting better at diagnosing it, we see the prevalence is much higher, and likely higher than almost any other valve disease," says Hahn.

Cardiothoracic surgeon Gorav Ailawadi, MD, MBA, FACC, agrees that the prevalence of TR is higher than previously thought. "There are differences of opinion and a lack of robust data, but we see patients with tricuspid valve disease as commonly as all the other valve diseases. It's just severely underdiagnosed."

Ailawadi is chair of Cardiac Surgery at the University of Michigan in Ann Arbor. He has served on the executive steering committees for numerous transcatheter and surgical trials in valvular disease and was the first surgeon in the U.S. to perform a MitraClip procedure.

Primary TR is caused by structural abnormalities of the valve itself, which can be related to valve degeneration or trauma, congenital anomaly, infection or an infiltrative process (tumors, drugs or radiation-related valvulopathy), and accounts for 5-10% of patients.

Far more common is secondary TR, where the valve structure is initially normal, but regurgitation occurs due to changes in the right ventricle (RV) or right atrium that result in leaflet malcoaptation. Secondary TR accounts for about 80% of patients, while TR related to cardiac implantable electronic device leads accounts for the remaining 10-15%.²

Recognizing that different TR etiologies may be associated with disparate outcomes, the Tricuspid Valve Academic Research Consortium has worked to expand the secondary TR classification by etiology. Atrial secondary tricuspid regurgitation (A-STR) is characterized by normal-appearing leaflets that fail to function properly in the presence of marked annular and atrial dilatation, often in the presence of longstanding atrial fibrillation (AFib). Patients with ventricular secondary tricuspid regurgitation (V-STR) have dilatation of the RV, leading to apical displacement of the papillary muscles.

As compared with V-STR, those with A-STR are more often women, more likely to have AFib and HFpEF, and less likely to have left-sided valve disease or pulmonary hypertension.²

Discriminating between the atrial and ventricular forms of TR has prognostic and treatment implications, says Hahn. Those with V-STR, for example, have higher mortality and a greater risk of hospitalization for HF. Perhaps more importantly, patients with V-STR may benefit from more aggressive treatment of their left-sided disease or whatever is causing their pulmonary hypertension, although the data are limited on this.

Subtle Symptoms and Suboptimal Echo

Many of the symptoms of TR are subtle and nonspecific. "I'd say the most common thing that patients describe is they run out of energy, they run out of gas. They can't do as much during the day. They do a few minimal activities and get tired and then have recuperate to do more later," says Ailawadi.

Along with the challenges of distinguishing the signs and symptoms of TR, the diagnosis of TR has been hobbled by persistently poor echocardiographic technique, says Hahn. It's the cardiac valve equivalent of using measures of leg strength to assess arm strength.

"Many echocardiographers are using left-heart metrics to assess the right heart, which you can't do because the left side is very high pressure and the right side is low pressure," explains Hahn.

"Color Doppler is based on momentum, which is based on pressure. High pressure on the left side will have a certain area of color that will not ever be seen on the right side because it's lower pressure. So, if you wait for the same measures of the color area on the right side, then you're looking at very severe, end-stage TR."

Transthoracic echocardiography (TTE) remains the primary imaging technique for identifying TR. However, Hahn has been working for 15 years to get the message out that color Doppler imaging should not be relied on as the primary method for assessing severity because of its tendency to underestimate TR.

Current echocardiography guidelines recommend a comprehensive, multiparametric and multimodal echocardiographic approach to assess TR, with the use of a 3-grade scheme (mild, moderate or severe) to describe the degree of regurgitation.^3,4 An extended grading scheme that includes severe (3+), massive (4+) and torrential (5+) has been developed to more precisely describe the severity of TR in patients undergoing transcatheter tricuspid intervention.⁵

"TR can easily be missed if the echo is not done carefully," says Ailawadi. "If a patient gets an echo ordered from their primary doctor, without mention nor concern about the tricuspid valve, the sonographers often will take very few images of the tricuspid valve or the readers will miss the TR entirely." Also, TTE can underestimate the degree of TR if there isn't careful image plane manipulation to identify the TR jet in its entirety.

Making diagnosis even more difficult is that the tricuspid valve is sensitive to fluid shifts, hence imaging patients in need of diuretics can result in overestimation of TR. "We always start patients on diuretics and get them optimized on medical therapy before we repeat the echo and start to think about a surgical or transcatheter intervention," says Ailawadi.

To get a sense of how specialized this all is, Ailawadi shared that of the 15+ echocardiographers at the University of Michigan, only two have been selected to do all the tricuspid imaging for the TTVI trials. "It's not simple, it's important and it's that subspecialized."

"We're aggressively trying to emphasize that the quantification of the disease, just like the quantification of aortic stenosis or mitral regurgitation, is crucially important for us to know how to move the patients forward for therapy," says Hahn.

Medical Management of TR

There are no Class I medical therapy recommendations to treat symptomatic severe TR in either the U.S. or European guidelines.^6,7 Medical management of TR primarily involves the use of diuretics, a Class IIa recommendation, and addressing the underlying causes of secondary TR, also a Class IIa recommendation.

"I can't tell you how many times I've been referred a patient with severe TR and they're not on any diuretic at all or they're on as-needed diuretics, despite it being known the patient has moderate or severe tricuspid disease," says Ailawadi.

Part of this persistent undertreatment is because the patients are asymptomatic or minimally symptomatic. They present with "just feeling a bit fatigued and perhaps some mild edema or feeling full in their abdomen," he says. "With these subtle symptoms, the tricuspid valve gets overlooked and patients are told their symptoms are just a sign of aging," he adds.

Diuretics can initially alleviate congestive symptoms but may lose efficacy due to factors like neurohormonal activation, increased diuretic distribution volume, impaired drug absorption due to visceral edema, and rebound sodium absorption.

For advanced disease, a stepwise approach is recommended, starting with loop diuretics to reduce volume load and pulmonary pressures (RV afterload), and adding mineralocorticoid antagonists in natriuretic doses to achieve decongestion, says Hahn in a review article on TR published in 2023.²

For those with secondary TR, comprehensive evaluation of pulmonary hypertension, left ventricular function, and rhythm control for AFib are critical. Right-heart catheterization is recommended for severe TR patients before any surgical or catheter-based interventions.

Hahn highlights that improving TR also improves HF, making a multidisciplinary approach to treatment very important. By including HF specialists in the team, it helps to avoid the "the trap of thinking that TR treatment is not part of treating HF."

There is also some evidence to show that in patients with left-sided HF and significant TR, the reduction in forward cardiac output caused by the TR can limit how aggressively their HF can be treated.

Conversely, while few have studied this, the available evidence indicates that improvement in left ventricular function also improves TR. In one study that looked at cardiac resynchronization therapy (CRT), about 41% of patients showed a reduction in severity of their TR with CRT.8 Reduction of mitral regurgitation with transcatheter treatments also appears to improve TR.

"I've seen patients go from severe TR to mild TR with optimized medical therapy, especially with SGLT2 inhibitors. It's so important that we see patients early, have an opportunity to assess their TR carefully and treat them with optimal medical therapy (OMT) before we consider any surgical or transcatheter intervention," says Susheel Kumar Kodali, MD, FACC, director of the Structural Heart and Valve Center at Columbia University Irving Medical Center/New York-Presbyterian Hospital.

Surgical Options

Traditional surgical interventions include tricuspid valve repair (annuloplasty) and tricuspid valve replacement with prosthetic valves. Repair is generally preferred over replacement. Surgical intervention is often considered in patients with severe TR and symptoms of right-sided HF, particularly when associated with left-sided valve surgery and this is supported by a Class I recommendation in the guidelines.

For isolated tricuspid valve surgery, a Class IIa recommendation is given for symptomatic severe primary TR or severe secondary TR in patients unresponsive to OMT, provided there is no pulmonary hypertension or left-heart disease. However, isolated surgical tricuspid valve replacement is associated with 12% or higher in-hospital mortality, primarily due to late presentation of patients with severe disease.⁹ Contemporary outcomes appear better, with one single center study (n=173; mean age, 60.3 years) reporting an in-hospital mortality of 4.1%.¹⁰

Ailawadi suggests that isolated tricuspid valve surgery can be performed with much lower operative mortality than historically reported. The trick is earlier intervention, careful patient selection, and 'prehabbing' patients with OMT before surgery. His group is soon to report a 0% mortality and less than 10% major complication rate with isolated tricuspid valve surgery in 75+ patients operated on at the University of Michigan over the last three years.

"The tricuspid valve is unique from other valves in that we think about transcatheter approaches first," he says. However, if the patient can only have surgery or is better suited for surgery, his preference is a minimally invasive repair through the right side on a beating heart to limit bleeding and ischemia to the RV. "We know that bleeding after surgery really hurts the RV. Then if you must give blood products to correct the bleeding, that further overloads the RV," says Ailawadi.

Transcatheter Options

Transcatheter tricuspid valve intervention (TTVI) offers a less invasive alternative to surgery for patients with significant TR. Several repair and replacement devices are under development, but only two have thus far received U.S. Food and Drug Administration (FDA) approval.

In February 2024, the FDA approved the Evoque transcatheter tricuspid valve replacement (TTVR) device (Edwards Life sciences) for the treatment of TR. A second approval followed in April when Abbott's TriClip transcatheter edge-to-edge repair (TEER) system received clearance.

Approval of the Evoque system was based on a prespecified analysis of the six-month results from the first 150 patients in the TRISCEND II pivotal trial. This trial included 400 patients with severe TR randomized to receive either Evoque or OMT.

While the rate of major adverse events was less than the expected rate (27.4% vs. 43.8%), early findings showed TTVR with Evoque effectively eliminated TR in a vast majority of patients (98.8% TR grade moderate or less) despite more than 55% having massive or torrential TR at baseline with the remainder categorized as severe, Kodali, who presented the TRISCEND II findings at TCT 2023, also notes that treatment of severe TR with the Evoque system resulted in meaningful improvements in functional status and symptoms at six months compared with OMT. One-year results for the entire patient cohort, which will include data on mortality and HF hospitalization, will be presented at TCT 2024.

"We'd like to see mortality benefit and we haven't seen one yet with either of the approved devices, but there are several factors that suggest the quality-of-life improvements we have seen are, one, related to the degree of TR reduction and, two, not a placebo effect," says Kodali.

Leveraging the experience in the mitral valve, tricuspid transcatheter edge-to-edge repair (T-TEER) is currently the most used TTVI option. TriClip approval was based on the TRILUMINATE trial, presented at ACC.23.¹¹

TRILUMINATE randomly assigned 350 individuals (mean age, 78 years; 55% women) with symptomatic severe TR at 65 centers across the U.S., Canada and Europe to receive either the TEER procedure with the TriClip device or continued medical therapy.

TEER was superior to medical therapy with a win ratio of 1.48 (p=0.02) for the primary endpoint, a hierarchical composite of all-cause death, tricuspid-valve surgery, HF hospitalization, and a significant improvement in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score (≥15 points) at one year.

Patients treated with TEER showed a mean improvement of 12.3 points on KCCQ vs. 0.6 points in the control group (p<0.001) at one year. At 30 days, 87.0% of the TEER group had TR of no greater than moderate severity, compared with 4.8% in the control group (p<0.001).

Other transcatheter strategies include annuloplasty (both direct and indirect) devices for patients with annular dilation as the primary mechanism of TR and mild leaflet tethering. Heterotopic valve implantation in the inferior vena cava or both inferior and superior venae cavae is considered for patients with appropriate caval diameters and preserved RV function, especially when no other direct valve treatment options are available.

TTVI require effective imaging guidance during the procedure, highlighting the contribution of interventional imagers. Better imaging of tricuspid valve anatomy and function during TTVI is provided by 3D intracardiac echocardiography (3D-ICE) and is emerging as a promising adjunct to transesophageal echocardiography (TEE) due to limitations in image resolution and field of view.¹² As operator experience with 3D-ICE grows, it is expected to play a more central role in tricuspid valve interventions, potentially improving procedural efficiency and patient outcomes.

“Advances in imaging are going to make this a more reproducible and effective procedure,” says Kodali. “This I what we saw with MitraClip with 3D-TEE and I suspect we’ll see the same with tricuspid intervention.”

Intervention Timing: 'Earlier is Always Better'

"Obviously, it's always best to treat patients before there are any sequelae from the TR, meaning liver or renal dysfunction that could be attributed to the tricuspid valve or RV failure," says Ailawadi. He notes that once moderate or greater RV dysfunction is seen, it's not clear if ventricular function will recover after treating the TR. "Earlier is always better for best outcomes."

This is where early referral to a multidisciplinary heart team at a valve center with significant experience in treating tricuspid disease comes in, he adds. An electrophysiologist needs to weigh in because a lot of the patients have AFib or pacemaker leads across the tricuspid valve. Also needed are experienced surgeons and interventionalists, a HF cardiologist who focuses on valves to help optimize HF treatment, and echocardiographers who are expert in imaging the tricuspid valve before and during intervention.

The 2020 ACC/AHA valvular heart disease guideline offers no recommendations on TTVI.³ The most recent European Society of Cardiology guideline, released in mid-2021, address transcatheter treatments only minimally.⁴ The authors suggest TTVI may be an option "at a Heart Valve Centre with expertise in the treatment of tricuspid valve disease" for patients with symptomatic secondary severe TR who are considered to be inoperable.

"I wouldn't say we have enough data yet to give transcatheter tricuspid intervention a Class I recommendation," says Kodali. "There is without a doubt real benefit, but we need to understand more about who to intervene on and when to use repair and when to use replacement," he notes. Right now, these decisions should be made by heart teams who are experienced in tricuspid interventions. Also, TTVI is "far more technically challenging" than transcatheter mitral intervention, he adds.

New Options Around the Bend

Tricuspid valve disease treatment is rapidly evolving, with new transcatheter techniques offering less invasive options for patients. Understanding the nuances of diagnosis and the timing and criteria for intervention is essential to optimize outcomes and prevent irreversible cardiac damage.

"I emphasize to patients that this field is changing very quickly, and new technologies are constantly emerging. Even if there isn't an option for a patient today, there might be one in six months. Keep in mind, none of the transcatheter options we're using now were available a few years ago," says Ailawadi.

References

1. Hahn RT, Weckbach LT, Noack T, et al. Proposal for a standard echocardiographic tricuspid valve nomenclature. JACC Cardiovasc Imaging 2021;14:1299-1305.
2. Hahn RT. Tricuspid regurgitation. N Engl J Med 2023;388:1876-91.
3. Zoghbi WA, Adams D, Bonow RO, et al. Recommendations for noninvasive evaluation of native valvular regurgitation. J Am Soc Echocardiogr 2017;30:303-71.
4. Lancellotti P, Pibarot P, Chambers J, et al. Multi-modality imaging assessment of native valvular regurgitation: an EACVI and ESC council of valvular heart disease position paper. Eur Heart J Cardiovasc Imaging 2022;23:e171-e232.
5. Hahn RT, Zamorano JL. The need for a new tricuspid regurgitation grading scheme. Eur Heart J Cardiovasc Imaging 2017;18:1342-43.
6. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease. J Am Coll Cardiol 2021;77:e25-e197.
7. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2022;43:561-632.
8. Stassen J, Galloo X, Hirasawa K, et al. Tricuspid regurgitation after cardiac resynchronization therapy: evolution and prognostic significance. Eur Eur Pacing Arrhythm Card Electrophysiol J 2022;24:1291-99.
9. Scotti A, Sturla M, Granada JF, et al. Outcomes of isolated tricuspid valve replacement: a systematic review and meta-analysis of 5,316 patients from 35 studies. EuroIntervention J 2022;18:840-51.
10. Shih E, George TJ, DiMaio JM, et al. Contemporary outcomes of isolated tricuspid valve surgery. J Surg Res 2023;283:1-8.
11. Sorajja P, Whisenant B, Hamid N, et al. Transcatheter repair for patients with tricuspid regurgitation. N Engl J Med 2023;388:1833-42.
12. Tang GHL, Zaid S, Hahn RT, et al. Structural heart imaging using 3-dimensional intracardiac echocardiography: JACC Cardiovascular Imaging Position Statement. JACC Cardiovasc Imaging 2024;June 6:[Epub ahead of print].

Clinical Topics: Valvular Heart Disease

Keywords: Cardiology Magazine, ACC Publications, Tricuspid Valve, Tricuspid Valve Insufficiency, Heart Valve Diseases