Transcatheter tricuspid valve replacement (TTVR) for symptomatic severe tricuspid valve regurgitation

Interventional cardiologists at Penn Medicine have introduced transcatheter tricuspid valve replacement (TTVR), a novel minimally invasive transcatheter procedure for the treatment of isolated tricuspid valve regurgitation.

About TTVR

The current management of tricuspid valve regurgitation (TR) is limited at every stage by a dearth of safe and effective treatments. Patients with progressive TR, for example, are excluded from surgery by a risk/benefit equation early on in the disease process that favors medical therapy (ie, diuretics). However, diuretics have historically failed to stem the long-term progression of TR. Patients with severe TR can opt for surgery, but rarely do, given the high in-hospital mortality (9-10%) for these procedures. [1, 2]

The success of TAVR and other transcatheter interventions for heart valve disorders in the last decade fueled the search for a percutaneous transcatheter device to replace the tricuspid valve. According to Paul Fiorilli, MD, who co-directs the Transcatheter Valve Program at Penn Medicine, a transcatheter approach that could eliminate or minimize the risks of an open heart procedure for TR would offer an ideal solution for the large population of patients with symptomatic severe tricuspid regurgitation.

TTVR can be said to be a descendant of transcatheter aortic valve replacement (TAVR), an interventional procedure brought to market by the investigators of the groundbreaking PARTNER trial, including Howard Herrmann, MD, and peers at Penn Interventional Cardiology. Penn interventional cardiologists participated, as well, in the development of transcatheter tricuspid valve replacement, or TTVR, as investigators in the global, multicenter, prospective, single-arm TRISCEND study of the EVOQUE valve, which took place at Penn Medicine and elsewhere. One-year results of TRISCEND demonstrated that an elderly, highly comorbid population with ≥moderate TR receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes. [3] The TRISCEND II clinical study, a global, prospective, multicenter, randomized, controlled, pivotal trial, led to the FDA approval of the EVOQUE device [4]

In addition to the EVOQUE TV replacement system (Edwards Lifesciences, Irvine, CA), which ultimately leads to resolution of TR, TTVR may be carried out as transcatheter edge to edge repair, or TEER. Penn Medicine also participated in the TRILUMINATE study of the Abbott TriClip system, which is now FDA approved for transcatheter tricuspid valve treatment, and represents another major tool in the arsenal to treat patients with TR. [5]

The EVOQUE system comprises a trileaflet bovine pericardial tissue valve implant and a percutaneous delivery system. The valve is delivered to the right ventricle via transfemoral venous access and positioned within the native tricuspid valve under real-time transesophageal echocardiography visualization. Once in position, anchors are exposed to engage the native leaflets, and subvalvular anatomy and annulus.

The current indication for TTVR, Dr. Fiorilli says, includes patients with symptomatic severe tricuspid valve regurgitation treated on maximally tolerated optimal medical therapy.

The forgotten valve

Tricuspid valve regurgitation (TR) manifests as incomplete closure of the valve leading to back flow of blood into the right atrium. First described by TW King in 1837, TR has persistently been depicted as a neglected and underestimated entity, [6] mired for generations in the misapprehension that severe TR was benign, and that treating left-sided heart disease would resolve right-sided tricuspid valve defects. [7]

Dr. Fiorilli notes that these elements earned for the tricuspid the descriptor the“forgotten valve.” While much about the prevalence, clinical significance, and management of TR remains at issue today, [Int J Cardiol Heart Vasc . 2024 Aug 22:54:101495] he adds, recent studies have brought about a reevaluation of the condition’s pathophysiology.

“Much of what we thought previously about tricuspid valve regurgitation, is changing,” he says. “We’re beginning to understand that TR has significant impacts on patients lives, and many effects on the body, including volume overload, fluid retention, and with increasing severity, cirrhosis of the liver.”

About TR

A minority of TR is primary, rooted in congenital heart disease or other disease states, trauma, or iatrogenic causes. The majority of patients, however, will have secondary disease, brought about by deformation of the valve through right ventricular or right atrial dilatation, leading to dilation of the dynamic annular ring and leaflet tethering leading to malcoaptation. Isolated TR, the most common form of the disorder (>90%), is a cause of tricuspid valve incompetence in the wake of anatomical and functional right heart chamber remodeling.[8]

TR is generally described as mild, moderate, severe, massive, or torrential (by echocardiography), with degrees of intensity between each of these stages. Mild (or trace) TR is a common incidental finding, and generally regarded as benign. Moderate TR is defined as a regurgitant volume of 30-44 ml with moderate dysfunction and remodeling. Severe TR has a regurgitant volume of 45-59 ml, and massive and torrential TR are defined by regurgitant volumes of 60-74 ml and >75 ml, respectively. For severe TR and above, this is often accompanied by right ventricular dysfunction and remodeling of the valve. Generally, morbidity and mortality parallel increasing severity of valve dysfunction.

Management of TR — beyond futility

Numerous challenges face providers treating tricuspid valve disease. Untreated severe TR carries a poor prognosis because in the absence of treatment, its many downstream effects (kidney, liver, and right ventricular dysfunction, among others) will progress. Progression is an issue with current medical treatment for TR, as well, because apart from drugs for the treatment of left-sided heart failure, medical therapy is limited to diuretics, which have historically failed to stem the progression of disease.

“At the outset of treatment, what we see is patients develop worsening volume retention and fluid overload treated with escalating doses of diuretics,” Dr. Fiorilli says. “This is a problem because patients can develop resistance to diuretic therapy over time, which can lead to heart failure exacerbations or significant symptoms affecting quality of life.”

Open surgical repair or replacement is indicated for patients with severe deterioration of the pulmonary, mitral, and aortic valves, but has a dismal history in patients with tricuspid disease.

“Surgical volume for isolated tricuspid valve surgery is very low nationally, because the morbidity associated with an isolated tricuspid valve repair or replacement is elevated, and rates of mortality are much higher than normally acceptable for surgical risk,” observes Dr. Fiorilli. Another complicating factor, he says, is that patients who have disease secondary to tricuspid regurgitation (for example, cirrhosis), may be at prohibitive risk for open heart surgery.

Thus, the advent of TTVR is a monumental advance in the comprehensive treatment of tricuspid valve disease.

Unique approach to TTVR at Penn Cardiology

Although recently FDA approved, TTVR is an established option for TR at Penn Medicine as a result of participation in the TRISCEND study. As a member of the implanting heart team in that study, Penn Chief of Cardiovascular Surgery Wilson Szeto, MD, has expressed the need to provide comprehensive multidisciplinary care for patients with TR in any clinical context, including TTVR.

Dr. Fiorilli took part in the first commercially approved transcatheter tricuspid valve replacement at Penn Medicine, which was also the first in the state of Pennsylvania.

“What we've observed in patients who have been treated with the EVOQUE valve is that patients’ quality of life has improved significantly,” he says. “Generally, diuretic requirements are decreased substantially and functional status is improved.”

Patients at Penn are evaluated with the Kansas City Cardiomyopathy Questionnaire score, which looks at symptoms, physical activity limitations, and patient reported quality of life and more objective measures like the six minute walk test. Both factors are improved in patients having TTVR, according to Dr Fiorilli.

Asked what makes the Penn Cardiology approach to TR unique, Dr. Fiorilli reflects that besides taking a patient-centered approach to tricuspid valve disease, the advent of TTVR means that the Division now has all of the treatment options available for patients with tricuspid valve disease, from medical therapy, to open heart surgery and the newest transcatheter tricuspid valve therapies.

“It’s a very exciting time to be at Penn,” he says.

Need to reach out to the Penn Valve Team?

Write to: PennValve@uphs.upenn.edu
Call: 215-662-4387

References

1. Zack CJ, Fender EA, Chandrashekar P, et al. National trends and outcomes in isolated tricuspid valve surgery. J Am Coll Cardiol 2017;70:2953–60.
2. Vassileva CM, Shabosky J, Boley T, et al. Tricuspid valve surgery: the past 10 years from the nationwide inpatient sample (NIS) database. J Thorac Cardiovasc Surg 2012;143:1043–9.
3. Kodak S, Hahn RT, Maker R, et al.Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study. Eur Heart J. 2023;44:4862-4873.
4. Grayburn PA, Kodali SK, Hahn RT, et al. TRISCEND II: Novel Randomized Trial Design for Transcatheter Tricuspid Valve Replacement. Am J Cardiol 2024;225: 171-177.
5. Sorajja P, Whisenant B, Hamid N, et al. Transcatheter Repair for Patients with Tricuspid Regurgitation. N Engl J Med 2023;388:1833-1842.
6. Guerin A, Dreyfus J, Le Tourneau T, et al. Secondary tricuspid regurgitation: Dowe understand what we would like to treat? Arch Cardiovascular Dis. 2019;112;642-651.
7. Sala A, Hahn RT, Kodak SK, et al. Tricuspid Valve Regurgitation: Current Understanding and Novel Treatment Options. JSCAI. 2023;2:101041.
8. L’Official G, Vely M, Kosmala W, et al.Isolated functional tricuspid regurgitation: how to define patients at risk for event? ESC Heart Fail 2023;10:1605-1614.