For ‘Torrential’ Tricuspid Regurgitation, Two New Transcatheter Devices Safe, Effective in Early Results

DENVER, CO—Two new transcatheter treatments for severe or greater functional tricuspid regurgitation (TR) are showing good efficacy and safety through 30 days, according to early feasibility study evidence presented here at TCT 2017.

Long deemed the ‘forgotten valve,’ the tricuspid has been gaining more attention with research increasingly linking severe TR and mortality risk. In early studies, devices designed originally for the mitral or aortic position have been tested in the large population of patients who previously have had no other treatment options—too old, frail, and high-risk for surgery.

The studies presented today represent some of the first research into dedicated devices for this condition.

Cardioband in the Tricuspid

Presenting results of the TRI-REPAIR study today, Georg Nickenig, MD (University of Bonn, Germany), explained that tricuspid regurgitation is predominately a consequence of RV and annular dilation. To treat this functional TR, his team tested the Cardioband tricuspid repair system (Edwards Lifesciences)—which performs tricuspid annular reduction via transfemoral access using the same concept as the Cardioband mitral system—in 30 symptomatic patients despite optimal medical therapy from nine European centers. Patients were a mean of 75.6 years and 86% were considered NYHA class III or IV at baseline. Almost all (93%) had A-fib and more than one-third had previous heart surgery.

Technical success was achieved in all patients, and there were no periprocedural deaths or severe major adverse events. At 30 days, two patients had died for reasons unrelated to the procedure.

There was an average 17% reduction in septolateral diameter from baseline to discharge (44.4 vs 37 mm; P < 0.01). At 30 days, echocardiography showed 50% and 31% reductions in proximal isovelocity surface area effective regurgitant orifice area (PISA EROA) and vena contracta measurements (P < 0.001), and a 7% improvement in LV stroke volume (P = 0.06) from baseline. These improvements resulted in most patients achieving TR of low or moderate severity at 30 days. Patients also saw functional improvement after treatment with the Cardioband, with 31 additional meters recorded in the 6-minute walk test (P < 0.05), a 7.1-point increase in KCCQ score (P = 0.06), and about 80% of patients classified as NYHA class I or II (P < 0.05) at 30 days.

“The use of the Cardioband system for tricuspid regurgitation seems to be feasible and safe,” Nickenig concluded. “It leads to significant annular reduction, [and] also reduction in TR. We’ve seen also some improvements in functional status.”

In a press conference, panelist Molly Szerlip, MD (The Heart Hospital Baylor, Plano, TX), said she is “excited about Cardioband in the mitral space but really excited about Cardioband in the tricuspid space.”

Questions remain, however. Although it is known that severe tricuspid regurgitation can lead to a higher risk of death, “we still really don’t know how much of a reduction or even if a reduction in tricuspid regurgitation then translates into improved mortality,” she said. “The surgeons don’t even know if they should treat it or not, especially if it’s moderate TR.”

Additionally, is reducing severe TR to moderate TR enough “or do you have to go to mild or do you have to go to none?” Szerlip asked. “It’s going to take a lot of time to come up with the answers.”

Filling the Space

In a second presentation, Susheel Kodali, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), reported results from the FORMA early feasibility study of the Forma tricuspid valve therapy system (Edwards Lifesciences). This device acts as a spacer positioned within the regurgitant orifice on which the native leaflets can coapt, and is on tracks that are anchored at the RV apex and the subclavian vein.

For the study, 30 patients with severe symptomatic TR from five US centers underwent implantation of the Forma device. One was unable to be treated due to subclavian vein disease, and there were two cases of RV perforation when the operator tried to position the anchor, one of which led to death. Of the 27 successfully implanted devices, one dislodged and the patient was sent to surgery and did not survive. Another patient had to have the device explanted due to infection after 3 weeks. Two additional patients reported anchor dislodgements, but the devices stayed in place at 30 days.

This patient cohort was also extremely sick. They were on average 75.9 years old, 86% were NYHA class III or IV, and 82.8% had A-fib. About one-quarter had a preexisting pacemaker, making implantation of the Forma device more challenging.

During 30-day follow-up, two patients died, one patient had a vascular injury, six patients reported major or life-threatening bleeding, three had a device-related cardiac surgery, and three reported acute kidney injury of stage 2 or greater. Echocardiography showed a halving of 2-D or 3-D quantitative effective regurgitant orifice area (2.1 vs 1.1; P = 0.012) from baseline, and patients with the worse TR at baseline seemed to show the greatest improvements. Seventy-two percent of patients were NYHA class I or II at 30 days and there were substantial improvements in both the 6-minute walk test and KCCQ scores.

The FORMA study proved the device is a “feasible therapy” for this patient population, although it “was associated with infrequent distal anchor dislodgements and the complications thereof,” said co-investigator Martin Leon, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), who presented the results during a press conference. “We would argue that the next generation of this device, which is being developed, needs to ensure more predictable anchor capture without dislodgement or RV perforations.”

Because “the magnitude of TR reduction seemed to be proportional to the severity of baseline TR, [this] may be an interesting device and most useful in those patients with the most severe degrees of TR,” he continued. “Clearly, we need longer follow-up to assess occurrence of TR, evidence of RV modeling, and late clinical outcomes.”

Szerlip said this is “another excellent device, [although] maybe a little more difficult to place than the Cardioband. . . . I find it just amazing how much of a 30-day improvement that you got [in TR].”

‘Coming Out of the Woodwork’

By way of background, Robert Yeh, MD (Beth Israel Deaconess Medical Center, Boston, MA), said in a press conference that part of the issue with patients with tricuspid disease “is that they haven’t been on the radar because we haven't had good therapies. There’s this mindset that ‘there’s nothing I can do about it,’ so they disappear off the map. Now that there are potentially new and promising therapies, I think that we will discover that this is a greater problem that maybe has been underappreciated in the past.”

“These are literally patients that people give up on, they say there's nothing to be done,” said press conference moderator Ajay Kirtane, MD, SM (NewYork-Presbyterian/Columbia University Medical Center).

Szerlip added that “these patients are going to begin to come out of the woodwork.” In medical school and residency, she said, she was “taught that there was no problem with severe TR. . . . As more of this comes out, people are going to realize, cardiologists are going to realize, that a lot their patients have it.”

With regard to the word “torrential” that both presenters used to describe the amount of TR in their patient populations, they explained that they had aimed include the very sickest patients in these early feasibility trial.

It’s hard to know exactly how many of these patients exist in the United States, Leon said. “Torrential” is a new term, he explained, used to describe the “patients who have much more than severe” TR. “Oftentimes with this disease, patients don’t express symptoms until they get beyond severe TR. . . . We do know that it's a substantial number that grows with age, and the surgical therapies are completely inadequate because of a high mortality for isolated tricuspid surgery in this population.”

Notably, 74% and 65.5% of patients in the TRI-REPAIR and FORMA studies respectively were women. Leon said researchers are still trying to understand why, but “epidemiologic studies [have shown] a suggestion that the prevalence of TR may be slightly higher in women. There may be some specific reasons for that, but certainly in our study it’s clear to us that there is no negative gender bias at least in this form of valvular heart disease.”

Note: Kodali, Leon, and Kirtane are faculty members of the Cardiovascular Research Foundation, the publisher of TCTMD.