Findings from the TAVR UNLOAD trial found preemptive TAVR was not superior to clinical aortic stenosis surveillance (CASS) for the hierarchical occurrence of all-cause death, disabling stroke, disease-related hospitalizations and heart failure equivalents, and change in quality of life among patients with moderate aortic stenosis (AS) and heart failure with reduced ejection fraction (HFrEF) who are already receiving guideline-directed medical therapy (GDMT).

The study, presented at TCT 2024 and simultaneously published in JACCby Nicolas M. Van Mieghem, MD, PhD, FACC, et al., randomized 178 patients to either TAVR or CASS between January 2017 and December 2022. The average age was 77 years, 20.8% were women and the median follow-up was 23 months. A total of 38 patients (43%) in the CASS cohort underwent TAVR at a median of 12 months post randomization.

Overall analysis of the hierarchical composite primary endpoint comparing patient pairs demonstrated "wins" for TAVR in 47.6% of pairs, "wins" for CASS in 36.3% of pairs, and "ties" in 16.1% of pairs at 23 months, resulting in an overall "win ratio" of 1.31 (95% CI, 0.91-1.88; p=0.143), according to the investigators. No statistically significant differences were observed between the TAVR and CASS cohorts in terms of the individual components of the composite endpoint (including all-cause mortality) either at 23 months or at one year. However, researchers noted that TAVR resulted in a greater improvement in the Kansas City Cardiomyopathy Questionnaire at one year, compared with CASS.

"Although the study was underpowered to adequately test the clinical benefits of TAVR in patients with HFrEF on GDMT with moderate AS, the outstanding procedural safety of TAVR in these patients and the immediate effects on quality of life may favor preemptive TAVR for select symptomatic patients," said Miegham, Elmariah and colleagues.

In a related editorial comment, Philippe Généreux, MD, FACC; Aakriti Gupta, MD, MSc, FACC; and Raj R. Makkar, MD, FACC, underscore the important insights gained from TAVR UNLOAD in terms of safety and the potential for improving quality of life. However, they write that the "broader question of whether preemptive TAVR in patients with moderate AS and preserved LV function improves long-term prognosis remains unanswered." They suggest that two larger, ongoing trials – EXPAND II and PROGRESS – may shed additional light on this issue.