After receiving reports regarding reduced leaflet motion in some bioprosthetic aortic valves, the FDA announced on Oct. 5 that the agency is working with the American College of Cardiology, the Society of Thoracic Surgeons and device manufacturers to design clinical studies to evaluate the situation.
The announcement occurred on the same day researchers published a study online in the New England Journal of Medicine that found 40 percent of a small group of patients enrolled in a transcatheter aortic valve replacement (TAVR) clinical trial and 13 percent of patients from two clinical registries had reduced leaflet motion. Patients in the registries underwent TAVR or surgical aortic valve replacement (SAVR).
St. Jude Medical and Cedars-Sinai Heart Institute funded the study. Lead author Raj R. Makkar, MD, of Cedars-Sinai, and colleagues used a 4D, volume-rendered CT to assess reduced leaflet motion.
They said that reduced leaflet motion appeared to be hemodynamically subclinical when detected, occurred in multiple prosthesis types and had a lower prevalence among patients receiving therapeutic anticoagulation compared with those receiving subtherapeutic or no anticoagulation. In addition, reduced leaflet motion was detected on CT or transesophageal echocardiography, but it was missed on transthoracic echocardiography.
“These findings, along with hypoattenuating opacities in the corresponding leaflets on two-dimensional CT, suggest that the reduced leaflet motion that we observed could be associated with subclinical leaflet thrombosis,” wrote Makkar and colleagues. “However, our study is limited by the absence of pathological confirmation, so the interpretation of reduced leaflet motion as thrombosis is based only on the imaging characteristics its resolution with anticoagulation.”
Although advanced imaging studies suggest blood clot deposits on the leaflets may cause restricted motion, the cause and occurrence rate of the reduced leaflet motion are not known, according to the FDA.
The FDA said that between 10 percent and 40 percent of TAVR patients and 8 percent to 12 percent of SAVR patients had reduced leaflet motion in the limited available information the agency had reviewed.
Most cases of reduced leaflet motion were found in patients without symptoms of abnormal bioprosthetic valve function. The FDA also noted there was acceptable forward blood flow through the valve opening and no evidence of stenosis in valves with reduced motion of at least one individual leaflet.
“At this time, FDA believes that bioprosthetic aortic valves remain reasonably safe and effective when used according to their approved indications,” the FDA said in a safety alert. “This view is supported by the favorable benefit/risk profile observed in SAVR devices in the 30 years they have been on the market and in TAVR devices in the 8 years they have been in use.”
The FDA said patients with a bioprosthetic aortic valve might want to undergo additional diagnostic imaging using 3D or 4D CT to determine if they have reduced leaflet motion.
“The reported phenomenon of reduced leaflet motion seen in bioprosthetic aortic valves is an early signal with unknown clinical significance,” the FDA said. “The FDA continues to closely monitor this signal and is working with the clinical community and device manufacturers to design studies to help us better understand the mechanism, incidence, risks, and consequences of reduced leaflet motion. This research also will help us determine whether there is a need for treatment and, if so, guide the appropriate treatment strategies. We will issue additional comments to the public when more information becomes available.”