FDA: Additional diagnostic imaging warranted to detect reduced leaflet motion in bioprosthetic valves

Issue: November 2015

The FDA issued a notification about recent reports of reduced leaflet motion in some bioprosthetic aortic valves, with a recommendation for additional clinical imaging using 3-D or 4-D CT or transesophageal echocardiogram when clinically indicated.

Further, if reduced leaflet motion is found, treatment options should be discussed with the patient’s heart team, according to the statement.

The notification comes in the wake of recent reports of reduced leaflet motion in valves used for transcatheter and surgical aortic valve replacement. Evidence from imaging studies suggests that thrombus deposits on the leaflets may cause restricted motion, according to the statement.

Recent evidence of reduced leaflet motion

In a study published in The New England Journal of Medicine in October, Raj R. Makkar, MD, from Cedars-Sinai Heart Institute, and colleagues analyzed data on 55 patients in the PORTICO IDE trial who underwent TAVR with the Portico valve (St. Jude Medical) compared with other transcatheter valves and 132 patients in the RESOLVE and SAVORY registries who underwent TAVR or surgical AVR.

“A finding of reduced aortic valve leaflet motion on CT in a patient who had a stroke after TAVR and similar findings in an asymptomatic patient at once clinical site led to closer scrutiny of this observation. Additional CT review by the core laboratory revealed that this finding was not isolated, which prompted a more extensive investigation that involved analysis of all available CT and echocardiographic data,” according to background information in the study. Thereafter, two physician-initiated registries — RESOLVE and SAVORY — were established to evaluate leaflet function after TAVR or surgical AVR.

CT scans revealed reduced leaflet motion in 40% of patients in the PORTICO IDE trial (43% with Portico valve; 43% with Sapien XT valves [Edwards Lifesciences]; 0% with CoreValve [Medtronic]) and 13% of patients in the pooled RESOLVE and SAVORY registries. The finding of reduced leaflet motion was detected across multiple bioprothesis types, including transcatheter and surgical, according to the results.

However, the incidence of reduced leaflet motion was lower among patients who were treated with warfarin compared with those treated with dual antiplatelet therapy (PORTICO IDE: 0% and 55%, respectively; P =.01; RESOLVE and SAVORY: 0% and 29%, respectively; P = .04).

“Reduced aortic valve leaflet motion … was easily detected noninvasively by [4-D], volume-rendered CT,” Makkar and colleagues wrote.

Twenty-one patients in the PORTICO IDE trial and the pooled registries had follow-up CT, 11 of whom had started or continued therapeutic anticoagulation. Restored leaflet motion was observed in all of the patients receiving anticoagulation compared with just one of 10 patients not receiving anticoagulation (P < .001).

Among patients in the PORTICO IDE trial, stroke or transient ischemic attack occurred in two of 22 patients with reduced leaflet motion and 0 of 33 patients with normal leaflet motion (P = .16). In the pooled registries, stroke or TIA occurred in three of 17 patients with reduced leaflet motion and one of 115 patients with normal leaflet motion (P = .007).

“The effect of this finding on clinical outcomes including stroke needs further investigation,” Makkar and colleagues wrote.

Bioprosthetic valves ‘reasonably safe’

The FDA stated that these reports have raised important questions about bioprosthetic valves. However, limited data do not allow the FDA to fully characterize the causes, incidence, and short- and long-term risks of reduced valve leaflet motion, or to recommend appropriate treatment.

“At this time, [the] FDA believes that bioprosthetic aortic valves remain reasonably safe and effective when used according to their approved indications. This view is supported by the favorable benefit/risk profile observed in [surgical] AVR 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 agency wrote.

The agency will work with the American College of Cardiology, the Society of Thoracic Surgeons and device manufacturers to design clinical studies to fully evaluate reduced valve leaflet motion for all types of bioprosthetic aortic valves, according to the statement. – by Rob Volansky

Reference:

Makkar RR, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1509233.

Disclosure: Makkar reports receiving grant support, personal fees and other support from St. Jude Medical; grant support from Medtronic; grant support and personal fees from Edwards Lifesciences; and other support from Entourage Inc. See the full study for the other authors’ relevant financial disclosures.