New Leaflet Thrombosis After TAVR Seen Out to 3 Years: OCEAN-TAVI

The latest attempt to understand the incidence, timing, and clinical importance of subclinical leaflet thrombosis following TAVR suggests that even though new cases appear to crop up over time, the majority of cases, left untreated, will have no impact on rates of death, stroke, or rehospitalization out to 3 years.

The new data, pulled from the OCEAN-TAVI registry, also showed that newly detected leaflet thrombosis was seen up to 3 years after the procedure, raising the question of just how long patients should be followed once leaflet thrombosis is detected.

The paper, by Ryo Yanagisawa, MD (Keio University School of Medicine, Tokyo, Japan), and colleagues, was published in the February 2019 issue of Circulation: Cardiovascular Interventions.

The occurrence and clinical significance of thrombus formation after TAVR remains unclear. To take a closer look at the phenomenon, Yanagisawa et al reviewed 4-D multidetector CT scans from 485 patients included in the OCEAN-TAVI registry. Scans were performed with the specific aim of looking for hypoattenuated leaflet thickening (HALT) with reduced leaflet mobility at 3 days, 6 months, and 1, 2, and 3 years post-TAVR. Importantly, when HALT was identified, no additional anticoagulation was prescribed, given the lack of clinical symptoms, allowing investigators to study the natural course of the phenomenon.

In all, early leaflet thrombosis was seen in nearly one in 10 patients (9.3%). For patients with balloon-expandable devices, independent predictors of HALT were low-flow, low-gradient aortic stenosis; severe prosthesis-patient mismatch; and use of a 29-mm prosthesis. For self-expanding prostheses, no independent predictors could be identified. Overall incidence of early leaflet thrombosis was similar with self-expanding and balloon-expandable TAVR devices. More thrombosis, however, was seen with Sapien 3 (17.9%) than with Sapien XT (4.1%; P < 0.001); the difference between Sapien 3 and CoreValve was not statistically significant.

Smaller numbers of patients underwent follow-up CT over the course of the study so that, by 2 years, imaging results were available for only 191 patients by 2 years and 65 patients by 3 years. Of note, however, 23 patients developed late-onset leaflet thrombosis (1 year), 18/191 at 2 years, and 11/65 at 3 years. Spontaneous resolution of leaflet thrombosis occurred in three patients without a change in the antithrombotic regimen.

The authors make a point of noting that no leaflet thrombosis was “newly observed” after the 3-year mark; however, occurrence of HALT continued, with some new cases appearing beyond 2 years. Moreover, almost two-thirds of patients in the cohort had not been followed beyond 2 years after TAVR, leaving it unclear from the current study just how long surveillance is warranted.

“Our data demonstrated that untreated early leaflet thrombosis did not affect the rates of death, stroke, and rehospitalization for heart failure,” the authors conclude, “Longer follow-up of this observation is needed to determine its occurrence and evaluate its clinical impact.”

Eager for More Data

Commenting on the study for TCTMD, Philipp Blanke, MD (St Paul’s Hospital, Vancouver, Canada), pointed out that the rate of leaflet thrombosis in OCEAN-TAVI is in keeping with a number of prior studies, a point also made by the study authors. It’s difficult to draw much in the way of conclusions from other study findings, he added—particularly with respect to the between-valve observations or the predictors of the thrombosis—since these have all been confirmed or contradicted by prior studies.

What’s novel in this paper, Blanke continued, is the observation of new late thrombosis among patients initially found to be negative for HALT on the predischarge CT. This “fits with the rest of the picture,” he continued. Prior work, he noted, has shown that even among patients whose thrombi resolve with warfarin, some will see the problem recur weeks or months later.

“This suggests that the phenomenon of leaflet thrombosis . . . can occur, it can vanish on its own without treatment, it can even come back at a later point, and it can actually involve different leaflets,” Blanke said. “I think the occurrence of late thrombosis, which has been documented here, actually fits nicely with the concept that leaflet thrombosis may be a dynamic process which may spontaneously wax and wane.”

That said, no new recommendations for management can be drawn from the study by Yanagisawa and colleagues, Blanke added. “There’s definitely no data to suggest that there is a need for anticoagulation and there is no data to suggest that there is a need for routine follow-up, at this point,” he said. “And this is in line with the findings of the GALILEO trial, which was put on hold. We do have to be very, very careful in regard to anticoagulation of patients in these cohorts because of the risk of associated bleeding. I don’t think there is currently enough evidence to make any recommendations.”

New information is expected from the CT substudies built into two, eagerly awaited, low-risk TAVR trials, one with the Medtronic Evolut TAVR device, the other (PARTNER 3) with the Edwards Lifesciences Sapien 3 valve. Main results for both trials will be presented at the upcoming American College of Cardiology Scientific Session, next month, although results for the CT substudies are not expected until the fall.

Even with these new data, however, the patient numbers are small, events are few, and answers may take time.

“I think the fact that we don’t see any clear signal for influence of leaflet thrombosis on patient outcome speaks to the fact that we are looking at a complex population with comorbidities where there are much stronger predictors of patient outcome than the finding of leaflet thrombosis,” Blanke said. “If we look in the lower-risk studies, with presumably younger patients involved, it may be different, but perhaps a follow-up of 2 years will not be enough. I think we’ll need longer follow-up if there’s a signal.”

A separate question is whether leaflet thrombosis will have more subtle effects on TAVR valve or leaflet durability. Here again, said Blanke, “2 or 3 years follow-up is not enough time.”