TAVR UNLOAD Shows Limited Benefit of TAVR in Patients With HFrEF and Moderate AS

October 28, 2024—Findings from the TAVR UNLOAD study found limited benefits of transcatheter aortic valve replacement (TAVR) in the treatment of heart failure with reduced ejection fraction (HFrEF) and moderate aortic stenosis (AS).

The TAVR UNLOAD findings were presented at TCT 2024, the 36th annual Transcatheter Cardiovascular Therapeutics annual scientific symposium of the Cardiovascular Research Foundation held October 27-30 in Washington, DC, and published simultaneously by Nicolas M. Van Mieghem, MD, et al in Journal of the American College of Cardiology.

According to the TCT press release, the investigator-initiated, international, randomized controlled trial enrolled patients with New York Heart Association (NYHA) class II to IV HFrEF (left ventricular [LV] ejection fraction ≥ 20% and < 50%) and moderate AS (aortic valve area > 1 cm² and ≤ 1.5 cm²) who were suitable for transfemoral TAVR with a balloon-expandable valve.

The TAVR UNLOAD analysis included 178 patients enrolled at 66 institutions in the United States, the Netherlands, and Austria from January 2017 to December 2022. The patients were randomized 1:1 to TAVR and guideline-directed medical therapy (n = 89) or guideline-directed medical therapy alone (n = 89).

The mean age of patients in the trial was 77 years, 20.8% were female, and 55.6% were NYHA class III or IV. The mean LV ejection fraction was 39%. During the study, 39% (n = 35) of the medical therapy group progressed from moderate to severe AS.

The TCT press release advised that the original design of the TAVR UNLOAD study required 600 patients (two groups of 300) with a primary endpoint analysis at 1 year. However, an updated protocol allowed for the use of the longest-available follow-up data, justifying a reduced sample size of 300 patients (two groups of 150). Because of funding limitations and slow enrollment, the steering committee decided to terminate enrollment by December 31, 2022, ensuring at least 1 year of follow-up for all participants.

The study’s primary endpoint was the hierarchical occurrence of all-cause death, disabling stroke, disease-related hospitalization, and heart failure equivalent, as well as the change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary score.

TCT reported that at 1 year, TAVR resulted in more wins driven by clinically meaningful improvement in quality of life compared with clinical AS surveillance (win ratio [WR] = 1.55 (1.04-2.31); P = .032).

However, TAVR did not affect the primary composite endpoint at a median follow-up of 23 months (WR, 1.31 [0.91-1.88]; P = .143). In addition, major adverse cardiac and cerebrovascular events (hazard ratio [HR], 0.83; 95% CI, 0.56-1.24; P = .36) and all-cause death (HR, 0.98; 95% CI, 0.61-1.56; P = .92) were not significant between the two groups.

“Although TAVR for moderate AS in patients with systolic heart failure on guideline-directed medical therapy was safe, it did not affect the primary hierarchical composite endpoint at a median follow-up of 23 months,” commented Professor Nicolas M. Van Mieghem, MD, in the TCT press release. “During the trial, > 40% of the surveillance group underwent TAVR predominantly because of disease progression from moderate to severe AS, which is more than we anticipated. The cardiac damage framework may identify a broader patient phenotype with moderate AS that may benefit from upstream TAVR and is currently under investigation in other trials.”

Prof. Van Mieghem is Professor and Clinical Director of Interventional Cardiology, Department of Cardiology, Cardiovascular Institute, Thoraxcenter Erasmus University Medical Center in Rotterdam, the Netherlands.