Subclinical leaflet thrombosis not tied to serious clinical events: PARTNER 3 CT substudy
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SAN FRANCISCO — In a CT substudy of the PARTNER 3 trial of low surgical risk patients who underwent transcatheter or surgical aortic valve replacement, hypoattenuated leaflet thrombosis and reduced leaflet motion were not associated with death, MI and stroke, according to data presented at TCT 2019.
The findings indicate that routine anticoagulation may not be necessary in patients with subclinical leaflet thrombosis as indicated by hypoattenuated leaflet thrombosis and/or reduced leaflet motion, the researchers concluded.
Among the cohort of 184 patients assigned TAVR with a balloon-expandable valve (Sapien 3, Edwards Lifesciences) and 162 patients assigned surgical AVR who had an evaluable CT, there was one clinical event at 30 days, a stroke, and six clinical events between 31 and 365 days in patients with hypoattenuated leaflet thrombosis, Raj R. Makkar, MD, the Stephen R. Corday, MD Chair in Interventional Cardiology, associate director of the Heart Institute and director of the interventional cardiology division at Cedars-Sinai, said during a press conference. The substudy was mandated by the FDA.
There were no cases of death or MI at 1 year in patients with hypoattenuated leaflet thrombosis, he said.
When the researchers pooled death, stroke, transient ischemic attack and thromboembolic events and compared them between patients who had hypoattenuated leaflet thrombosis at 30 days and those who did not, the event rates were numerically but not significantly higher in the leaflet thrombosis group between 7 and 365 days (8.6% vs. 2.9%; P = .11), between days 7 and 30 (2.9% vs. 0.3%; P = .19) and between days 31 and 365 (5.7% vs. 2.6%; P = .27), Makkar said.
“Given the low total number of events, the data are inconclusive and only hypothesis-generating,” he said. “Longer-term follow-up and a larger data set will further clarify the impact on clinical outcomes.”
Hypoattenuated leaflet thrombosis was more common in patients who had TAVR than in patients who had surgery, and the difference was significant at 30 days (13.3% vs. 5%; P = .03), although not at 1 year (TAVR, 27.5%; surgery, 20.2%; P = .19), he said. In the overall cohort, leaflet thrombosis was present in 10% of patients at 30 days and in 24% of patients at 1 year.
Of note, he said, among patients who had leaflet thrombosis at 30 days, 56% no longer had it at 1 year, and none of those whose leaflet thrombosis disappeared were on anticoagulation, and among patients who did not have leaflet thrombosis at 30 days, 21% developed it by 1 year.
“What we found was that hypoattenuated leaflet thrombosis and reduced leaflet motion were frequently present in bioprosthetic valves,” Makkar said during the press conference. “Hypoattenuated leaflet thrombosis is a dynamic finding, with spontaneous resolution in more than 50% and new appearance in more than 20% of cases.”
Reduced leaflet motion was observed in all patients with hypoattenuated leaflet thrombosis, and the impact of leaflet thrombosis on gradient was “minimal,” Makkar said.
During a panel discussion, Makkar and other experts said the findings cast doubt on the practice of routine anticoagulation for subclinical leaflet thrombosis.
“What surprised me is the percent that resolved without anticoagulation,” Michael J. Mack, MD, FACC, co-investigator of the PARTNER 3 trial and medical director of cardiovascular surgery at Baylor Scott and White Health, said during the discussion. “The impact of all this is that we are not justified recommending routine anticoagulation. It does call into question the recommendation in the guidelines for surgical valves. That was made based on smaller observational studies. Now that we have routine surveillance for surgical valves, it calls into question whether we need 3 months of anticoagulation.” – by Erik Swain
Reference:
Makkar RR, et al. Late-Breaking Trials 2. Presented at: TCT Scientific Symposium; Sept. 25-29, 2019; San Francisco.
Disclosures: PARTNER 3 was funded by Edwards Lifesciences. Makkar reports he consults for and receives research grants from Abbott, Boston Scientific, Edwards Lifesciences and Medtronic. Mack reports he consults for W.L. Gore and Associates and serves as study chair or co-principal investigator for trials sponsored by Abbott, Edwards Lifesciences and Medtronic.
Perspective
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David J. Moliterno, MD, FACC
The observations from the PARTNER 3 cardiac CT substudy are intriguing. Beyond TAVR, we have not systematically looked at surgical valves post-implantation with CT; just like how years ago, we didn’t look at relatively fresh bypass grafts systematically. When we started doing minimally invasive bypass surgeries and wanted to check the graft patency early on, we would see haziness and narrowing at the anastomosis site, which was likely attributed to edema. Similarly, here, we have a systematic study looking at post-TAVR and post-surgical valves and a substantial portion, around 20%, at 1 year have leaflet attenuation.
Another interesting point is to have an accurate quantification of the valve leaflet thickening. This phenomenon, so-called hypoattenuated leaflet thrombosis, may be an innocent bystander, but that is not clear. We need to look at these patients years down the road to see if there is any impact or association between hypoattenuated leaflet thrombosis and valve durability. This may be an early marker of a late valve problem, but time will tell.
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Robert O. Bonow, MD
This issue is still a work in progress. The study looked at leaflet thrombosis that is subclinical, and there is not much of a risk for stroke or valve dysfunction, although I wonder how much leaflet thrombosis will factor in late structural valve deterioration, both in the TAVR valves and in the surgical valves. Makkar showed that even when only one leaflet is involved, it affects the hemodynamic performance of the valve. We need to know whether this translates into something later.
We are not recommending anticoagulation or high-tech CT imaging for everybody yet, but this will play out when we get longer-term data. The good news is, there are clinical trials underway that will tell us more about the anticoagulation issue. Standard practice is dual antiplatelet therapy, and there is a class 2A recommendation for vitamin K antagonists for 3 to 6 months in patients with a surgical valve, and also a class 2B recommendation for at least 3 months after TAVR. We don’t yet fully know if this is the direction we should go in for TAVR.
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