Knowns and Unknowns in Subclinical Aortic Valve Thrombosis

Bioprosthetic valve thrombosis found on imaging—with no symptoms reported by the patient—presents a conundrum for clinicians. What are the odds a given case will ultimately impact hemodynamics, potentially impairing durability, and what if anything should be done?

A new review, published online recently ahead of print in Circulation: Cardiovascular Interventions, sums up the literature on incidence, mechanism, diagnosis, and optimal management.

Lead author Kalyan R. Chitturi, DO (MedStar Washington Hospital Center, Washington, DC), speaking with TCTMD, said he and his colleagues wanted to pull together what’s known—and what’s not—about the topic in both transcatheter and surgical valves.

The review comes on the backdrop of advances in cardiac computed tomography angiography (CCTA) as well as trial designs that increasingly include standardized CT surveillance. Both have raised the question of how to handle subclinical bioprosthetic valve thrombosis, namely hypoattenuated leaflet thickening (HALT) and reduced leaflet motion (RLM), when it’s detected. Stroke risk is the more immediate concern, though these CT findings may also raise flags for diminishing valve performance over the ensuing years or decades.

Jonathon Leipsic, MD (University of British Columbia/St. Paul’s Hospital, Vancouver, Canada), said “it’s one of more thoughtful reviews I’ve seen on the subject,” in that it covers the work done by VARC-3 in characterizing valve thrombosis as well as insight from mechanistic, observational, and randomized studies.  “It’s a very nice go-to piece for people in the broader community that really want a soup-to-nuts [summary] of what we’ve learned” since the first reports on the topic emerged in 2015.

Gilbert Tang, MD (Mount Sinai Health, New York, NY), said that the “no one knows” how much subclinical valve thrombosis truly matters. Even in low-risk patients, these cases “come and go,” he said. “The rate is definitely higher than what we probably should be seeing—it’s over 20%—[but] some disappear, and some appear. So we just don’t know what kind of conditions, whether it’s patient, anatomic, device-related, or procedure factors, we can pinpoint to better prevent this from happening.”

For clinicians wading through the evidence base, it’s helpful to have all the information in one document, Leipsic and Tang agreed. The review offers an algorithm, for instance, with guidance on how to diagnose and manage bioprosthetic valve thrombosis, which Chitturi noted is especially helpful in subclinical cases, “where the area is much more gray.”

How Much Does HALT Matter?

With follow-up from low-risk TAVI trials now available beyond 5 years, “we're seeing that the whole idea of management of HALT really needs a paradigm shift in thinking,” said Chitturi. Up-front prophylaxis with anticoagulant therapy appears to offer “little to no benefit in terms of stroke prevention [but] a real risk of bleeding,” Chitturi said. The data suggest “maybe we were too aggressive with stroke prevention [through] anticoagulation.”

Now, with evidence from GALILEO and other studies, there’s a shift away from universally giving anticoagulation to all TAVI patients. When patients have an indication for anticoagulation, studies suggest a direct oral anticoagulant may be better than a vitamin K antagonist.

Prophylactic anticoagulation “can increase undue harm with bleeding, especially in patients who are at high surgical risk and elderly,” Tang told TCTMD. That said, it “may be reasonable” to offer 3 months of anticoagulation to younger patients who are better able to tolerate it, he added. For those without an indication for anticoagulation, though, the POPular TAVI trial shows a single antiplatelet is sufficient.

When subclinical cases do occur, they don’t always progress to clinical issues and sometimes can resolve. In the PARTNER 3 CT substudy “a lot of the low-grade HALT disappeared upon longer-term follow-up up to a year. But then, within that year, new cases of HALT developed,” Chitturi pointed out. “That shows that HALT is a dynamic process. It's still poorly understood.” The Evolut Low Risk trial stands as another example: nearly three in 10 patients had HALT at 1 year, the review notes, but less than half a percent had clinical valve thrombosis by 3 years.

Both of these low-surgical-risk trials of TAVI versus SAVR had protocols for CT surveillance, said Chitturi. Because of this, “we were also able to see that there was actually a higher rate of subclinical leaflet thrombosis after bioprosthetic SAVR than had previously been reported in the literature. It was very underreported. Now we have a greater understanding that it's an entity that not only affects transcatheter heart valves, but also bioprosthetic surgical valves, and may have an impact on their durability long term as well.”

Once higher gradients are in play, whether that “portends a worse clinical outcome in terms of bioprosthetic valve dysfunction and failure is to be determined,” he added. “It is a controversial area. If we extrapolate from the surgical literature, it may play a role, but the jury is still out. We do not know.”

With HALT, “we still don’t entirely understand whether this is important to cover and whether it’s clinically relevant or not,” Leipsic agreed, noting that evidence is currently mixed on whether HALT is associated with higher risk of future degeneration. “But I think the field continues to want to understand.” If there is a link, he added, then “does identifying it early and treating it prevent that progression to valve degeneration? Or is it already too late?”

Leipsic pointed out that half the time HALT does go away on its own. Going forward, it will be important to track how various strategies for addressing the condition affect longer-term outcomes, he said.

Along with the algorithm, the review does offer some other advice.

“Major advances over the past 5 years in diagnosing and understanding the clinical implications of subclinical leaflet thrombosis have informed a more conservative approach to surveillance and treatment. Based on the best available evidence, patients who have undergone TAVR or bioprosthetic SAVR should undergo focused and comprehensive clinical assessment and evaluation of bioprosthetic valve function with [transthoracic echocardiography; TTE] at their follow-up visits,” the authors write.

CCTA, on the other hand, “should be reserved for patients with clinical thromboembolism or abnormal hemodynamics on TTE due to the harm of unnecessary anticoagulation outweighing any treatment benefit for low-grade HALT or RLM,” Chitturi and colleagues conclude, saying that therapeutic oral anticoagulants should be reserved for use in severe HALT or RLM with hemodynamic valve deterioration or clinical valve thrombosis.

At this point in time, the best path is annual surveillance with TTE after AVR, Tang also specified. “The cardiologist should do an echo to look for any signs of gradient increase that are unexpectedly high or any kind of change in the valve measurements in terms of leakage. Those are early signs we need to look into further.”

When HALT is identified, “there’s no consensus right now” about what to do, said Tang. “If there’s no change in echo gradients or hemodynamics, I think most people would say, ‘Leave it alone.’” But with some early data suggesting the condition could lead to long-term durability issues, a short 1- to 3-month bout of anticoagulation might be helpful as a way to nip it in the bud, he suggested. Whether some aspects of this phenomenon are irreversible, though, remains to be seen.