Valve Leaflet Thrombosis: Treat It or Leave It Be?

CHICAGO, IL—The clinical significance of valve leaflet thrombosis with or without reduced leaflet mobility continues to be debated, with experts reaching little in the way of agreement as to what, if anything, should be done about the problem.

Lars Søndergaard, MD, DMSc (Rigshospitalet, Copenhagen, Denmark), speaking at TVT 2017, gave an overview of the recent research in this area, noting that despite the growing consensus that anticoagulation may help prevent and resolve leaflet thrombosis, other emerging data hint the problem may resolve on its own in many patients.

“The clinical consequences are uncertain with regards to progression to clinical thrombosis, stroke/TIA, and valve durability,” he said.

Søndergaard and colleagues have a paper in press at the European Heart Journal, some of which he has also previously presented at TCT 2016, looking at the natural history of this phenomenon: isolated valve leaflet thrombosis, known as hypo-attenuated leaflet thrombosis (HALT), which Søndergaard characterized as “the more mild condition,” as well as the more serious form of leaflet pathology, namely reduced leaflet mobility or hypo-attenuation affecting motion (HAM). Søndergaard and colleagues looked the natural history of HALT and HAM across five different TAVR valves (CoreValve first-generation, Evolut R, Portico, Lotus, and Sapien 3) and two surgical bioprostheses (Perimount and Trifecta).

They performed CT scans at baseline and roughly 3-4 months later in all patients, finding evidence of leaflet thrombosis in 30.1% of the transcatheter valves and 28.2% of the surgical valves. There were no differences between transcatheter and surgical devices and no significant differences between brands.

Leaflet mobility, however, was found in 19% of TAVR devices and just 3.9% of the surgical valves.

Søndergaard et al then looked at changes between CT scans and made some interesting observations. In all, 53 out of 105 patients who had no evidence of HALT or HAM on the initial CT scan remained free of the problem at follow-up, but seven patients with no leaflet thrombosis on the first scan were found to have it on the second. An additional four patients with clear initial CT scans went on to develop the more serious problem of abnormal leaflet motion.

However, on the flip side, five patients who had leaflet thrombosis on the first CT had no evidence of this on the second scan and an additional four patients with both HAM and HALT on the first CT actually had their motion abnormalities resolve, although leaflet thrombosis remained in two of the four.

Importantly, in this analysis the researchers did not change or prescribe any medications based on the diagnosis made at the first scan. “If a patient was on antiplatelet therapy, we continued with that, if a patient was already on an anticoagulant, we continued with that,” Søndergaard explained to TCTMD.

“And what you see is that it’s not so simple, that if you just give anticoagulation it’s going to disappear,” he continued. “If you just leave it, some will disappear and some which was normal at the first instance will be abnormal at the later incidence. So as I see it, in the lifespan of a bioprosthetic valve, it may be normal at one point, go up to HALT, go up to HAM, go back to HALT, go back to normal, maybe several times during its lifespan. And if you [appreciate] that you have this natural history, I don’t think it’s the definitive cure just to put the patient on anticoagulation, because while it may resolve, the minute you stop the patient could still be at risk to progress to HALT and HAM.”

Guideline Update Allows for Drug Therapy

Søndergaard’s wait-and-see approach—at least until more evidence comes in—is at odds with a recent update to the AHA/ACC valvular heart disease guidelines. In March, guideline writers issued a number of changes to their 2014 document, among them a new Class IIb recommendation noting that anticoagulation with vitamin K antagonists “may be reasonable for at least 3 months after TAVR in patients at low risk of bleeding.” That advice is based on studies documenting valve thrombosis, found on CT scanning, that developed in patients antiplatelet therapy alone but not in patients who were treated with VKA.”

That new guidance appears to have caught some TAVR operators off guard, particularly the seemingly arbitrary recommendation of 3 to 6 months.

Raj Makkar, MD (Cedars Sinai Medical Center, Los Angeles, CA), also speaking at TVT 2017, has led much of the research into this new and evolving field and was largely supportive of the new recommendations, although he questioned whether the 3 months would be adequate. To back up his position, he recapped for his TVT audience data that he previously presented at the American College of Cardiology 2017 meeting, as reported by TCTMD. This analysis, which combined data from CT scans in 890 patients enrolled in the RESOLVE and SAVORY registries, showed that the prevalence of reduced leaflet motion in patients following transcatheter or surgical valve replacement was significantly lower among those who were taking oral anticoagulation than in patients who received DAPT (3.6% vs 14.9%; P < 0.001). 

Makkar says he now believes that 3 months of anticoagulation “is not enough.”

At this point, he continued, “I’d be inclined to go ahead and give this for 6 months. That’s just based on the fact that 3 months is not enough; there’s no evidence to say that 6 months will be any better.”

Beyond the uncertainty of how and whether to treat leaflet thrombosis/mobility problems is whether to even go looking for them in the first place.

Martin Leon, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), who chaired a session devoted to the issue, observed: “I think most people agree that doing systematic CT follow-up scans is simply a bridge too far, but when we talk about the thresholds for performing CT [and] deciding when to do a CT scan, I’m still a little bit confused.

Makkar, in response, suggested that outside of clinical trials, CT imaging can be “offered” but not routine. “I think that the only argument you can make for CT is when someone’s got a clinical reason to do one. So if someone has a TIA or a stroke, or if they have new heart failure but even a small increase in gradient: those might be the reasons to do a CT. We’ve had cases where patients had mild symptoms and if you actually do [CT] and you find something and you treat them with anticoagulation, their symptoms get better. So I think there is no reason to do this routinely. The question is, should that threshold change as we start to treat really young people? I think that’s open to question.”

Søndergaard, a panelist in the same session, stuck to his guns, however, reminding the audience that there is no definitive proof that subclinical leaflet thrombosis plays a causative role in TIA, or stroke, or valve durability. “So for the time being I think we need more evidence before we change clinical practice to treat patients with anticoagulation based on these findings,” he stressed. “It may be an innocent bystander.”

To TCTMD, Søndergaard pointed out that one of the chief arguments for bioprosthetic valves, surgical or transcatheter, is that they spare younger patients from needing to take anticoagulation long-term.

“A bioprosthetic valve, is in many ways a less durable valve than a mechanical valve, because mechanical valves have excellent durability,” he said. “So if you are then going to give the patient anticoagulation, why give them a transcatheter bioprosthetic valve?”

He continued: “’I think, for the time being, we should stay calm. Let’s say, ‘Okay, we see something, let’s try and get more information.’ Don’t panic, and don’t [withhold] the TAVI, because it’s been a lifesaving treatment for a lot of patients.”

Leon, chairing the session, seemed to agree with a wait-and-see approach.

“There has been a bit of a rush to judgment here, and seeing the guidelines change I think has caused people to be taken aback a bit. And I think it’s going to hasten the adoption of therapies that themselves may introduce morbidity and complications,” Leon said. “I do think we need more data but it is interesting to see how quickly this has taken hold.”

He noted that “several thousand” patients are being followed for leaflet thrombosis and reduced mobility in clinical trials. “Within a year or two . . . we’re going to have some evidence that might allow us to develop more rigorous recommendations based on prospective rather than retrospective data,” Leon predicted.

Both of the low-risk TAVR trials for the Sapien 3 and the Evolut R include leaflet mobility substudies that involve cardiac CT. Two additional trials, GALILEO and ATLANTIS are studying the use of non-vitamin K oral anticoagulants (rivaroxaban and apixaban, respectively) to prevent valve thrombosis and other events in patients who have undergone transcatheter aortic valve replacement. The studies are designed to enroll approximately 1,500 patients each.