Transcatheter Aortic Valve Replacement in Patients With Systolic Heart Failure and Moderate Aortic Stenosis: TAVR UNLOAD

Background: Neurohormonal modulation and afterload reduction are key for treatment of heart failure with reduced ejection fraction (HFrEF). In HFrEF patients with concomitant moderate aortic stenosis (AS), treatment with transcatheter aortic valve replacement (TAVR) may be complementary to guideline-directed medical therapy (GDMT). Objectives: This study sought to determine whether TAVR for moderate AS provides clinical benefit in patients with HFrEF on top of GDMT. Methods: We performed an investigator-initiated, international, randomized controlled trial in patients with HFrEF on GDMT with moderate AS who were suitable for transfemoral TAVR with a balloon-expandable valve. Patients were randomized 1:1 to TAVR or clinical aortic stenosis surveillance (CASS) with aortic valve replacement upon progression to severe AS. The primary endpoint was the hierarchical occurrence of: 1) all-cause death; 2) disabling stroke; 3) disease-related hospitalizations and heart failure equivalents; and 4) change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score analyzed using the win ratio. Results: From January 2017 to December 2022, 178 patients were randomized to TAVR (n = 89) or AS surveillance (n = 89). The mean age was 77 years, 20.8% were female, and 55.6% were in NYHA functional class III or IV. The median follow-up duration was 23 months (Q1-Q3: 12-33 months). A total of 38 (43%) patients in the CASS group (of whom 35 had progressed to severe AS) underwent TAVR at a median of 12 months postrandomization. TAVR was associated with wins in 47.6% of pairs, compared with 36.6% in the CASS group, resulting in a win ratio of 1.31 (95% CI: 0.91-1.88; P = 0.14). At 1 year, TAVR resulted in a greater improvement in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score compared with the CASS group (12.8 ± 21.9 points vs 3.2 ± 22.8 points; P = 0.018). Conclusions: TAVR was not superior to AS surveillance for the primary hierarchical composite endpoint in patients with moderate AS and HFrEF on GDMT. Preemptive TAVR for moderate AS was safe and may provide clinically meaningful quality-of-life benefits.