Transcatheter Cardiovascular Therapeutics conference 2011: Live link of UK case highlights FDA’s caution on Sapien Aortic Valve PMA.

Medical Device Daily reports on the current state of play regarding drug eluting stents, transapical valves and highlights FDAs cautious approach to the latter as UK live link shows placement of device four years after CE mark approval.

The article goes on; Physicians in attendance at this year’s edition of Transcatheter Cardiovascular Therapeutics (TCT 2011) are having a tough time getting through the third day’s events without being reminded of late-stent thrombosis (LST) in drug-eluting stents and the accompanying firestorm.

The response to LST by both FDA and patients was palpable to say the least, and any encouraging data in connection with the Sapien aortic valve, made by Edwards Lifesciences (Irvine, California) are consequently being served up with reticence. This description can be applied even to the presentation by Martin Leon, MD, of Columbia University Medical Center (New York), who served as the principal investigator for the Placement of AoRTic TraNscathetER Valve (PARTNER) trial, the pivotal study of the device for FDA’s review. Leon, who might have been described as ebullient upon presentation of the Partner data at last year’s edition of TCT, said that all of the five classes of complications associated with catheter delivery of aortic valves can be managed by one means or another, and he concluded, “we should proceed . . . with caution.”

One of the more fascinating events at this year’s edition of Transcatheter Cardiovascular Therapeutics was a video feed from St. Thomas’ Hospital (London) of the insertion of a Sapien aortic valve via the transapical/minithoracotomy approach, which was followed by a feed from Columbia University Medical Center (New York) of a transfemoral delivery of a Sapien. Leon remarked at one point during the procedure at Columbia “I think at some point we’ll see dedicated closure devices” for the transfemoral exit, a procedure that is said to take nearly as much time as the valve placement, “but we’re not there yet.”

Leon also let loose what might be seen as a slap at FDA regarding the approval of the Sapien, saying “for me its been an odyssey” to get to the issuance of a PMA for the Sapien, he added that these videos are “the first live cases we’ve been able to transmit from the U.S, and we’ve joined the international community” in using the device outside a pre-market trial.

Leon observed that one of the dilemmas facing doctors regarding artificial valves for the aorta is how aggressively physicians will work to properly seat the valve in an effort to tamp down on leaks, and conversely how much paravalvular leakage a physician will see as tolerable, given the heightened risk of stroke associated with repeated manipulations of the device undertaken to suppress leaks.

“This is still only a four-year experience” with the Sapien, Leon remarked, an acknowledgment of the device’s CE mark of 2007, “so we have to put that in perspective” in discussions of complications. He noted that of the more than 17,000 experiences in EU nations, most are surgical procedures, not transfemoral. The surgical literature “is a very dirty literature” in terms of stroke rates, he said, but he also argued that ascertainment and adjudication of strokes is a bit complicated due in part to definitional variance. A post-hoc analysis by Edwards of stroke data fed some of the conflict between the firm and the agency at the advisory committee hearing earlier this year (Medical Device Daily, July 22, 2011), and Edwards’ position was that many of the events captured and defined in the trial were asymptomatic strokes of little or no clinical consequence.

Leon referred to the differences in stroke rates between surgical and transcatheter procedures, but he also highlighted a composite endpoint. “If you combine stroke and mortality” from PARTNER, “you can see there is no significant difference,” he said. Leon concluded his remarks on stroke by stating that manipulation of the device is a factor, testifying, “I don’t think it’s an unmanageable complication.”

Regarding the paravalvular leak issue, Leon said one study conducted in France indicated that “congruence of the annulus and the valve” is a driver of leaks, “but clearly calcification is an important consideration” as well. He mentioned this in the context of a study of the Medtronic (Minneapolis) entrant into this market, the CoreValve, remarking that leakage is associated with increased mortality and hence “not something we can just ignore.” He added that in this case, too, definitions are inconsistent – as is the rubric for grading of leaks – but he assured the audience that operator experience will at least mitigate the leakage issue. “I think we will be able to manage this, but I give it a yellow light,” he concluded.

Significant vascular complications encountered in the early going demonstrate an association with mortality, but Leon indicated that here, too, definitions vary, although he is of the view that these events are too high by any definition. He said that among these are some instances of valve dissection and some incidents of hematoma, but vessel perforations also showed up in meaningful numbers. Some of the PARTNER data indicate the risk of death is nearly double for patients with vascular complications vs. those with none, but Leon was confident “we’re going to be able to solve this problem.”

Leon also acknowledged the incidents of permanent pacing in some patients receiving aortic valve replacements, although this has been reported as a more commonplace event with the CoreValve. He said blockage of the right bundle branch is a predictor of permanent pacing to address left bundle blockage associated with the procedure, but one study Leon cited showed that device positioning into the aorta’s outflow tract is a co-predictor along with blockage of the right bundle branch. The positioning issue presumably refers to the proximity of the aortic valve to the atrioventricular (AV) node and the potential for a device to exert pressure on the AV node, downstream of which the bundle branches lie.

Leon said in his view, “the major concerns are stroke and durability.” He said he is “encouraged by the embolic protection devices” designed to solve some of the stroke issue, and wanted to see them in trials “quickly.”

Source: Medical Device Daily