Pathological Study of HALT Confirms Importance of Early Detection and Treatment of Thrombus on Valve Leaflets

September 17, 2022—Medtronic announced findings from its pathological study of hypo-attenuated leaflet thickening (HALT) in self-expanding transcatheter aortic valves (TAVs). The HALT study is part of the company's CoreValve/Evolut transcatheter aortic valve replacement (TAVR) systems program.

The study compares microCT and histology findings of valve leaflet thickening, the results of which may provide clinical insights for long-term durability of TAVs and treatment of HALT.

As noted in the Medtronic press release, HALT is observed on CT imaging and indicates possible formation of a blood clot on prosthetic heart valve leaflets, potentially affecting their ability to open and close freely. HALT may occur in at least 10% of TAVR patients and can impact valve deterioration. Although HALT can typically be treated with oral anticoagulants (OAC), it is sometimes resistant to drug therapy.

The findings were presented as Late-Breaking Clinical Science in Structural Heart Disease at TCT 2022, the 34th annual Transcatheter Cardiovascular Therapeutics scientific symposium of the Cardiovascular Research Foundation held September 16-19 in Boston, Massachusetts. The study's conference abstract, TCT-325: "Pathology of Hype-Attenuated Leaflet Thickening (HALT) in CoreValve/Evolut Self-Expanding Transcatheter Aortic Valve Bioprosthesis" by Yu Sato, MD, et al is available online in the conference supplement of the Journal of the American College of Cardiology.

Dr. Sato, study investigator at CVPath Institute in Gaithersburg, Maryland, commented in the press release, "These findings help to address the need to better understand HALT development and treatment, particularly in cases where OAC therapy fails. Further, we believe these findings underscore the need for early detection and treatment within the first year after implantation. This may help to optimize outcomes for patients receiving transcatheter aortic valves.

According to Medtronic, the study evaluated the extent of pathologic changes of valve thrombosis, neointimal thickening, inflammation, and calcification over time in 110 TAVs explanted at surgery or autopsy. The explanted valves were collected from 11 clinical studies that included more than 7,500 participants. Additionally, the study also evaluated areas of leaflet thickening by two methodologies, microCT and histology, to assess the prevalence, length, and underlying cellular composition of these areas.

The company noted that clinical thrombosis rates are extremely low (0%–1.3%) in CoreValve/Evolut clinical trials of self-expanding TAVs.

But the study found that approximately 45% of leaflets in explanted valves showed at least some degree of leaflet thickening; the prevalence was comparable with microCT and histology assessment.

The investigators observed that histological scores by implant duration showed there was no change in thrombus and inflammation scores over time; however, neointima, structural changes, and calcification scores increased with greater implant duration. Thrombi begin organizing after 30 days and by 1 year had a more organized morphology that may be resistant to treatment, reported Medtronic in the press release.

Medtronic's CoreValve Evolut R, CoreValve Evolu Pro, and Evolut Pro+ TAVR devices are indicated for relief of aortic stenosis in patients with symptomatic heart disease caused by severe native calcific aortic stenosis who are judged by a heart team, including a cardiac surgeon, to be appropriate for TAVR therapy.

Nina Goodheart, Senior Vice President and President of the Structural Heart & Aortic business, which is part of the Cardiovascular Portfolio at Medtronic, stated in the press release, "As TAVR continues to grow as a treatment option for aortic stenosis, identifying pathological changes to TAVs over time is critical for understanding their long-term durability. Today’s results offer additional clinical evidence for our CoreValve Evolut Program to better understand the importance of early treatment when HALT is detected."