Valve Thrombosis in TTVR Not Uncommon: Meta-analysis

Approximately one in nine patients develop leaflet thrombosis in the first 10 months after transcatheter tricuspid valve replacement (TTVR), according to a meta-analysis. Most cases are subclinical, but researchers say they may yet be tied to future problems, so it’s important to keep tabs on the complication as the treatment’s use expands.

Led by Mark J. Zorman, BM, BCh (Oxford University Hospitals), the study was published recently as a research letter in JACC: Cardiovascular Interventions.

“We’ve known about leaflet thrombosis affecting TAVR valves for some time. We know that it’s not a unique process to valves in the aortic position or transcatheter valves—it affects all bioprosthetic valves in the heart at a varying incidence rate,” senior author Thomas J. Cahill, MBBS, DPhil (Oxford University Hospitals, England), told TCTMD.

Therefore, it’s not a surprise to see thrombosis in the tricuspid setting, Cahill said. “It’s a low-pressure valve, and it’s the right side of the heart, [where] there’s more stasis compared to the left side, so there’s less washout,” he explained. “I think it is inevitable that there is going to be some leaflet thrombosis. It’s a question of how big a problem it is and how best do we manage it.”

While the rate of leaflet thrombosis they found is “appreciable,” most cases were subclinical without the presence of valve dysfunction that causes symptoms for patients, he said. “What is the relevance of that? Is leaflet thrombosis on the tricuspid valve a precursor to structural valve degeneration?”

Importantly, unlike in aortic valve replacement, with TTVR it’s routine for patients to receive oral anticoagulation, Cahill pointed out, though there’s no consensus thus far on whether warfarin or a direct oral anticoagulant (DOAC) is best, either for prevention or treatment.

This study doesn’t give clues on the best approach, Cahill noted. “Should we screen for leaflet thrombosis? And if we see leaflet thrombosis, should we change patients from DOACs to warfarin? Is there a difference between those two?”

What’s clear, though, is that the level of leaflet thrombosis seen here should not deter from pursuing TTVR, “because the rate of clinical thrombosis is very low,” said Cahill, who added, “We are in the early stages and phases of a very exciting, transformative field, and we had an expectation there would be [some] leaflet thrombosis.”

We are in the early stages and phases of a very exciting, transformative field, and we had an expectation there would be [some] leaflet thrombosis. Thomas J. Cahill

Azeem Latib, MD (Montefiore Medical Center, Bronx, NY), who did not take part in the new study, agreed that it’s not a surprise to see more valve thrombosis in therapies addressing the right side of the heart, especially given the larger frame size of devices for tricuspid versus aortic disease. This is why anticoagulation is so universal in this population, though the best duration—whether lifelong or along the lines of 6 to 12 months—hasn’t been identified, he said.

“We figured [leaflet thrombosis] was going to be a problem,” said Latib. “What we don’t know is how big a problem this is going to be. Will it be the Achilles’ heel of TTVR or will it just be one of those things that we need to know [about]? . . . We shouldn’t shy away from it.”

The finer points of TTVR are likely to see more scrutiny as the procedure is adopted more widely. In March 2025, the US Centers for Medicare & Medicaid Services agreed to reimburse TTVR in symptomatic tricuspid regurgitation. A year prior, the Food and Drug Administration approved Evoque (Edwards Lifesciences) as the first TTVR system to be cleared for marketing in the United States.

85% of Thrombosis Cases Subclinical

Zorman and colleagues included eight studies—three prospective, two retrospective, and three case series—whose populations added up to 176 patients (mean age 73.7 years; 79.5% women). Comorbidities included atrial fibrillation (67.6%), chronic kidney disease (46.0%), diabetes (12.5%), and prior cerebrovascular events (5.7%). Mean STS PROM score was 9.0, and the mean LVEF was 58.0%.

Seventy-nine patients received TricValve (P&F Products & Features), 65 Evoque (Edwards Lifesciences), 21 TriCento (NVT), six LuX-Valve (Jenscare Scientific), three Sapien XT (Edwards Lifesciences), and two TRiCares (TRiCares). All were given oral anticoagulation following TTVR: 34% vitamin K antagonists, 16% DOACs, and 50% an unspecified type.

Total follow-up was 150.2 patient-years, and mean weighted follow-up was 10.2 months. Overall, there were 15.8 cases of valve thrombosis per 100 patient-years, with 8.5 and 14.0 events per 100 patient-years of clinical and subclinical cases, respectively. This translated to 1.7% of patients developing clinical valve thrombosis and 9.7% subclinical valve thrombosis during follow-up.

One unknown in these data is whether the leaflet thrombosis appeared while a patient was on anticoagulation or if perhaps they’d paused their medication in the wake of a bleeding event, Cahill observed to TCTMD.

Researchers saw a nonsignificant trend toward numerically more cases of valve thrombosis with porcine versus bovine pericardial valves (10.6 vs 15.3 events per 100 patient-years; P = 0.57), but no difference between orthotopic and heterotopic valves.

“The challenge with this type of [analysis] is we’re limited by the studies that are out there. They’re heterogeneous in terms of the valve design, the way they’ve screened for valve thrombosis, and the use of anticoagulation, so it’s very difficult to draw definitive conclusions about valve choice, valve leaflet composition, or anticoagulation strategy. But it frames how important it is going to be going forward to understand those types of issues,” said Cahill.

We need to really carefully study TTVR thrombosis. It’s a reality. Azeem Latib

Latib pointed out that, at least anecdotally, operators know that thrombosis is more likely to arise after TTVR when a patient is on a DOAC rather than warfarin. Less certain is what to do when one develops. In a patient who’s stopped warfarin, it makes sense to restart the medication, which will likely resolve the issue, he advised. “If it happens on a DOAC, I’ve switched patients from a DOAC to warfarin, and in most of them I’ve been able to get rid of it. But I have had one patient—and I’m sure if I’ve had one, other people have had one—where the valve had to be removed because we couldn’t get rid of the thrombus on the valve.”

For Latib, there are numerous limitations to the report that are worth noting. “It’s a multitude of devices,” he said, noting, too, that the meta-analysis includes smaller studies with varying designs but not the TRISCEND II pivotal trial.

Still, Latib stressed, the new paper is a reminder that “we need to really carefully study TTVR thrombosis. It’s a reality.” He highlighted the TRIPLACE registry as a useful data source on this and other topics.

Next steps, Cahill specified, include searching for risk factors that foretell the development of thrombosis and determining what can be done to mitigate that risk and treat the condition once it occurs. A key aspect is the balance between bleeding and thrombotic risks. That’s important given that many patients tend to be referred late in the disease process and are on anticoagulant therapy, which makes them especially vulnerable to bleeding.

“To be honest, we’re still figuring it out on the aortic side—it’s not an easy one,” Cahill acknowledged, adding that larger studies of TTVR thrombosis with consistent approaches to screening and diagnosis are needed.