Leaflet Restriction After TAVR: Two Hospitals Tracking Patients Find Similar Rates of the Phenomenon

LONDON, England—Two sets of investigators tracking signs of leaflet thickening among patients undergoing TAVR at their respective centers have come up with surprisingly similar rates of the phenomenon. 

Results from the small, single-center studies were presented here earlier today at PCR London Valves 2016.

In the first, Robert Gooley, MD (Monash Heart, Melbourne, Australia), reported results for 70 patients treated with the Lotus valve (Boston Scientific) who underwent 320-slice CT assessment at 30 days, 6 months, 12 months, 24 months, and 36 months. Transthoracic echocardiography and clinical assessment were performed at the same time points.

“Thickening of TAVI leaflets and resultant restriction of motion has recently been described,” Gooley explained. “But the time frame of onset and clinical sequelae are still being determined.”

In all, 11 out of 70 patients (15.7%) were found to have leaflet thickening and reduced leaflet mobility. In most, just one leaflet was affected, but four patients had two affected leaflets and one patient had three affected leaflets.

Timing also was variable. Initial imaging pointed to leaflet thickening and restriction in eight patients, but in three patients leaflet thickening was not evident until 1 year—and in one case 3 years—had passed.

While there were no significant differences between the normal-leaflet and leaflet-thickening groups, Gooley highlighted the fact that none of the patients who developed thickening were taking anticoagulation at the time of their scans, as compared with 20% of patients who did not develop leaflet abnormalities. Of note, however, stroke was rare in the entire cohort and no strokes occurred in the leaflet thickening group over the follow-up out to 1 year.

Where the investigators did see a difference was in hemodynamics: patients with evidence of leaflet thickening showed a significance increase in mean aortic gradient following hospital discharge, as compared to patients with no thickening. There was also a trend towards smaller effective orifice area in the thickening group.

One of the 11 patients who was found to have leaflet thickening developed a very sharp increase in mean gradient and was put on warfarin. By 1 year, the gradient had resolved to roughly the same levels as the other patients also found to have leaflet restrictions.

“In this cohort of 70 patients treated with the Lotus prosthesis, leaflet thickening was observed in 15.7% of the cohort and was identified at variable time points following implantation,” Gooley concluded. The phenomenon was not associated with subsequent stroke but did appear to have hemodynamic significance, he said, and anticoagulation “appeared to be protective.”

HALT: What Goes There?

In a separate presentation, Ryo Yanagisawa, MD (Keio University School of Medicine, Tokyo, Japan), reported on a series of 70 patients treated with the balloon-expandable Sapien XT (Edwards Lifesciences) who underwent multidetector CT at discharge, 6 months, and 1 year. One patient was found to have hyperattenuated leaflet thickening (HALT) at hospital discharge, seven patients at 6 months, and a cumulative total of 10 patients at 1 year—a rate of 14.2%.

Male sex, larger sinus Valsalva size, and larger prosthesis size were all associated with an increased incidence of HALT. Perhaps more tellingly, patients with HALT were also found to have significantly higher levels of D-dimer at both 6 months and 1 year, but not at the time of hospital discharge.

Of note, mean pressure gradients were actually marginally lower in the HALT group than in the non-HALT group.

“D-dimer may be useful for screening for possibly THV thrombosis,” Yanagisawa said, concluding, “A prospective study in a larger cohort and comparison with other bioprosthetic valves would be relevant.”

Future Steps

Following both presentations, session co-moderator Alexandra Lansky, MD (Yale University, New Haven, CT), pointed to parallels between the two studies. “What’s striking to me is consistency in the rate of [leaflet thickening] . . . Both around 15% at 12 months,” she said.

Jonathan Byrne, MB ChB, PhD (London Bridge Hospital, London, England), the other session co-moderator, called the findings “very timely” and asked Gooley whether he and his colleagues had looked at any device-specific factors that might be linked to leaflet restriction or thrombosis. “One of the things we’re going to have to look into as we get more and more cohorts with different valves,” Byrne said, “is [whether] there any differences in the way these devices are being prepared, porcine versus bovine pericardium, length of time that these are crimped in the catheter, are we damaging the leaflets during the procedure—lots of questions.”

Similarly, Paul Hsien-Li Kao, MD (National Taiwan University Hospital Yun-Lin Branch, Taipei), asked whether the group had analyzed leaflet thickening/restriction in relation to procedural characteristics, including number of repositioning maneuvers or retractions. 

In response, Gooley said his group has not yet done these analyses, although he noted that all of the repositions were just “partial repositions, so in that setting you are not really taking the leaflets back into the catheter, so the number of complete repositions are low, and that’s where you might see that you are damaging leaflet tissue.”

Gooley pointed out that a number of trials are addressing the anticoagulation question in the setting of leaflet restriction and thrombus formation; his group is continuing to follow their patients with serial imaging. In one patient with reduced gradient on echo who also had renal impairment—precluding serial CT tests—operators were able to identify leaflet thickening by transthoracic echocardiography.

Both of the recently announced low-risk TAVR randomized controlled trials are including substudies in approximately 400 patients to look specifically at the issue of leaflet thickening and thrombosis.

“We do need larger cohorts,” Gooley said. “It’s a condition we have identified without clinical sequelae. We can’t oversell the condition now, but we need to research it more so we can be aware of what happens in the longer term. And as we move into lower- and intermediate-risk cohorts, this is going to become more important.”

In the current study, investigators saw no strokes among the leaflet restriction group, but whether that lack of an association remains after 10 years remains to be seen, he added.

Asked by Lansky whether “leaflet restriction equals thrombosis,” Gooley called this a leap, but not an implausible one, given the gradient resolution in the patient treated with warfarin in his series.

Also, he said, “we’ve seen this in explanted surgical bioprostheses,” among patients undergoing repeat procedures for failing prosthetic valves. “Yes, there’s a degree of pannus formation, but there are some of these surgical bioprostheses that do have thrombus on them as well. To make another leap, perhaps we will be able to help our surgical colleagues—some of those patients may have been treated with therapeutic anticoagulation and avoided the reoperation of their surgical bioprostheses.”