The recent progress in interventional cardiology has largely been driven by the aortic valve, although calcification of the aortic root has proven a difficult hurdle to overcome. A newly published study demonstrates that the Tendyne device by Abbott Vascular Inc., of Santa Clara, Calif., can be readily used not just to treat failing mitral valves, but works well in these patients with severe calcification, an achievement that could quickly vault the transcatheter approach past conventional surgical approaches in this population.
Abbott reported in July 2018 it had commenced enrollment into a pivotal U.S. study for the Tendyne, a repositionable/retrievable device that will be evaluated in the Summit study of more than 1,000 patients with mitral valve regurgitation. The company reported at the same time that it would enroll a feasibility study of the device in treatment of patients suffering from severe mitral annular calcification, a study that would enroll 30 subjects, although the latest journal article in the Journal of the American College of Cardiology reports returns for only nine of those patients.
The nine patients – five men and four women – were at an average age of 77 years at enrollment, and the devices were all delivered via the transapical route. The authors said device implant was successful in all nine cases, although one patient developed left ventricular outflow tract obstruction when the device rotated out of position, requiring septal ablation. The average follow-up in this group was a year, although one patient was followed to 28 months, and cardiac death accounted for only one of the two fatalities. The authors said clinical improvement with mild or no symptoms was seen in all patients who were still alive at the end of the follow-up period.
TAVR devices associated with 25% mortality
The authors noted that mitral annular calcification (MAC) can invade the myocardium, which in turn can lead to the nearly universally fatal atrioventricular groove disruption. Invasion of the myocardium was seen in seven of the nine patients reported. Some of the more commonplace co-morbidities at enrollment include atherosclerosis of the coronary arteries and renal failure, and thus these patients are at high risk for poor surgical outcomes. The use of valves for transcatheter treatment of the aortic valve have proven to be fairly effective off-label treatments, but there are problems with this approach, including left ventricular outflow tract obstruction and a 30-day mortality of about 25%.
This feasibility study excluded patients with severe tricuspid valve regurgitation, pulmonary hypertension, and either left ventricular ejection fractions of no greater than 30% or end diastolic diameters of 70 millimeters or less. The patients were treated in France, Germany and the U.S., including at least one at Emory University Hospital in Atlanta.
The Tendyne is a fairly complex design, consisting of an outer nitinol frame that houses an inner frame to which the trileaflet porcine valve tissue is attached. The authors noted that the outer frame is "contoured to the fit of the mitral annulus," a feature said to facilitate sealing to the annulus sufficiently to obviate the need for oversizing to prevent paravalvular regurgitation. The local heart team in this study was left to decide whether to pre-dilate the valve, however, a consideration that has been seen as at least a modest confounder in studies of other transcatheter valve therapies. The authors said that while four of the nine patients were discharged to skilled nursing or rehab facilities, the remaining five patients went straight home after discharge.
The authors said that at last follow-up, eight patients were ambulatory and had improvement in their heart failure grades. No evidence of device malfunction was demonstrated, including no demonstrated stenosis, thrombosis or hemolysis. No major clinical adverse events were seen, the authors said, adding that the epicardial pad of the Tendyne not only relieves the need for oversizing, but also reduces any concerns about a need to circularize the mitral annulus.
Abbott acquired the Tendyne device via its 2015 acquisition of Tendyne Holdings at a time when the Mitraclip device was still the sole commercially available mitral valve repair device in the U.S., a title it holds to this day. The Mitraclip is now in its fourth iteration, although competition for non-valve repair is starting to heat up. Boston Scientific Corp., of Marlborough, Mass., recently wrapped up its acquisition of Millipede Medical, which was developing a semi-rigid annuloplasty ring for transfemoral delivery. By some estimates, the global market for devices for mitral valve repair and replacement will reach $1 billion sometime over the next two years.
Previous studies avoided calcification
In an accompanying editorial, Josep Rodés-Cabeau and François Dagenais, both of the Quebec Heart and Lung Institute in Quebec City, Canada, noted that patients with severe calcification have usually been excluded from trials for dedicated transcatheter mitral valve repair (TMVR) systems. They noted that roughly 30 patients had been screened for this feasibility study, and that at least some of the exclusions were due to new-onset left ventricular outflow tract issues.
Rodés-Cabeau and Dagenais said the investigators "should be congratulated for leading this important initiative," which they said could lead to a paradigm shift in the treatment of "this challenging group of patients." They said the small size of the study takes some of the sheen off the results, but noted that the 100% rate of complete resolution of regurgitation coupled with the absence of early device mortalities "invites readers to be optimistic." Still, they said, there are caveats, including that the investigators had excluded patients with pulmonary hypertension and tricuspid disease. This, Dagenais and Rodés-Cabeau said, had some bearing on the affirmative results of this study, but should nonetheless "inform the design of future studies in the field."
While the authors of the editorial noted that the Tendyne avoids some of the problems with balloon-expandable valves and their reliance on radial force and valve circularization to seal off any regurgitation, they described the use of a transapical approach as a "significant drawback." One consideration is that transapical access is still associated with access hemostasis problems, adding that any instances of apical myocardial injury could hamper left ventricular function, particularly in patients with already-problematic contractility.
Rodés-Cabeau and Dagenais also observed that the Tendyne has been associated with measures taken to address left ventricular outflow tract problems, but stated that the results indicate that "the transcatheter field may offer a more reliable alternative to open surgery for patients" suffering from severe mitral valve calcification.