The unexpected and unwelcome detection of reduced leaflet mobility in transaortic valve replacements is back in the spotlight thanks to a study of the phenomenon in the New England Journal of Medicine. The paper reveals some tantalizing clues about the technical issue, but it remains mysterious, and the FDA is maintaining its stance that "bioprosthetic aortic valves remain reasonably safe and effective when used according to their approved indications."
The reduced leaflet mobility was detected a little more than a year ago by advanced 4-D CT scan imaging conducted during the FDA clinical trial of St. Jude's ($STJ) Portico TAVR. It resulted in a safety scare that led to the rare withdrawal of a device's CE mark and temporary suspension of the Portico's clinical trial for FDA approval.
|St. Jude's Portico transcatheter aortic heart valve--Courtesy of St. Jude|
But the Portico's CE mark was reinstated in March and the FDA clinical trial was allowed to resume in June, for further investigation was unable to link the mechanical problem to poor clinical outcomes. Also, additional advanced imaging found that the problem was not limited to the Portico TAVR, which worked in the device's favor.
But that only made the reduced leaflet mobility an even more important topic for further research.
The just-published study in the New England Journal of Medicine inspected Portico clinical trial data as well as two data registries created after the technical issue was originally discovered. The study's investigators detected reduced leaflet mobility in 16 of 37 Portico patients (43%), 6 of 14 patients on Edwards' ($EW) Sapien XT (47%), and 0 of 4 patients on Medtronic's ($MDT) CoreValve valves.
The study found a statistically significant correlation between stroke and reduced leaflet mobility. The observed incidence of stroke or TIA (transient ischemic attack) in patients with reduced leaflet mobility was 3 out of 17 patients, compared to 1 out of 115 patients with normal leaflet function.
That result comes with several caveats though, starting with a small sample size. And all of the strokes occurred within a day of the TAVR procedure and before 4-D CT imaging was performed, which makes it unlikely that the adverse events were related to reduce leaflet mobility. "It is more likely that these first-day strokes were related to the procedural aspects of TAVR rather than to leaflet thrombosis," the paper says.
Interestingly, anticoagulation therapy restored normal leaflet mobility in 11 out of 11 patients, while the technical problem remained in 9 out of 10 patients who did not receive warfarin or another blood thinner. "Normalization of leaflet motion with anticoagulation also suggests that thrombus formation is the primary event leading to reduced leaflet motion rather than reduced leaflet motion leading to the formation of an overlying thrombus," the paper says.
"If replicated across other valve programs and non-thrombotic causes are ruled out, the data would suggest initiating anticoagulation treatment routinely in all TAVR cases unless contraindicated," Dr. Sanjay Kaul of Cedars-Sinai Medical Center in Los Angeles told MedPage Today. And due to the recent approval of many alternative blood thinners to warfarin, which anticoagulant to use could also become the subject of debate.
It's important to note that the reduced leaflet mobility could be a phenomenon in not just TAVRS but surgically implanted valve replacements as well, for the issue was only detected due to the adoption of advanced imaging technology that was not used or was not available during previous clinical trials.
The paper says that in addition to CT scans, imaging using transesophageal echocardiography can also detect the technical issue.
Despite all of the caveats and uncertainties, "our findings raise the concern that patients undergoing TAVR or surgical aortic-valve replacement with a bioprosthetic valve could be at greater risk for leaflet thrombosis and consequent embolic stroke than has previously been recognized," the study authors wrote.
Still the FDA said it cannot recommend appropriate treatment due to the limited data available; reduced leaflet mobility remains a phenomenon with "unknown clinical significance" in the eyes of the agency.
Dr. Kaul concurred with the FDA's approach, telling MedPage Today that, "overall, the quality and quantity of data are insufficient to evaluate the clinical relevance of the findings or to justify a hasty action by the regulatory agencies. However, it is appropriate to raise the awareness and increase vigilance."