FDA Approves TAVR for Low-Risk Aortic Stenosis Patients; Chinese Experts Urge Caution Due to Anatomical and Clinical Differences

Source: Chinese Circulation Journal

On August 16, the U.S. Food and Drug Administration (FDA) approved the balloon-expandable valves Sapien 3 and Sapien 3 Ultra (Edwards Lifesciences Corporation) and the self-expanding valves Evolut R and Evolut PRO (Medtronic) for use in low-risk patients with severe aortic stenosis.

With this, TAVR has unlocked every door in the treatment of aortic stenosis. However, is it feasible to promote TAVR among low-risk patients in China? In what areas will future TAVR therapy require further refinement or breakthroughs?

The widespread adoption of TAVR in low-risk patients is primarily driven by the strong support from the PARTNER 3 trial (balloon-expandable valve) and the concurrently published EVOLUTE Low-Risk study (self-expanding valve).

However, the PARTNER 3 trial excluded patients with bicuspid aortic valves, those with contraindications to transfemoral access, and those with poor cardiac function (left ventricular ejection fraction <30%).

In a previously published commentary in this journal on the PARTNER 3 trial, Wu Yongjian and Wang Yuan from Fuwai Hospital pointed out that Chinese patients are characterized by severe leaflet and annular calcification, a high prevalence of bicuspid aortic valve, and more serious access vessel complications, which to some extent limits the applicability of its findings to Chinese patients.

Transcatheter Valve Replacement in Low-to-Moderate Risk Patients in China: Significant Challenges, Prudent Approach, and Promising Future

Regarding future focal points for TAVR, Wu Yongjian and colleagues believe that the next hotspots in clinical research will likely be head-to-head comparisons in low-to-intermediate-risk patients (balloon-expandable valves vs. self-expanding valves) and investigations into valve durability.

First, younger patients are more common among low-risk populations; they have a longer life expectancy and thus impose higher requirements on the durability of implanted valves. Furthermore, although transcatheter heart valves share structural similarities with surgical bioprosthetic valves, they possess distinct characteristics such as the retention of native valve leaflets and a crimped state prior to deployment. Consequently, the durability of transcatheter heart valves is a subject of significant concern.

Subclinical Thrombosis Associated with Valve Deterioration: An Information Gray Zone for Low-Risk Surgical Patients. The investigators of the PARTNER 3 trial comprehensively considered CT assessments of transcatheter heart valve leaflet motion, among other factors, in anticipation that forthcoming study results will address this critical knowledge gap.

In summary, preventive and therapeutic explorations for TAVR valve failure have never ceased. The development of anti-calcification and antigen-removal valves, the modification and optimization of antithrombotic treatment regimens, the use of vitamin K antagonists for subclinical thrombosis, and “valve-in-valve” or “valve-in-valve-in-valve” procedures for treating failed bioprosthetic valves all aim to safeguard the expansion of indications to low-risk patients.

Source:

[1] Megan Brooks. FDA Expands Approval for TAVR Valves to Low-risk Patients. Medscape. August 16, 2019.

[2] Wu Yongjian, Wang Yuan. A New Era in the Treatment with Transcatheter Aortic Valve Replacement: Insights from the PARTNER 3 Clinical Trial. Chinese Circulation Journal, 2019, 34: 632-634.