Findings from the TAVR UNLOAD study found limited benefits of transcatheter aortic valve replacement (TAVR) in the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) and moderate aortic stenosis (AS).
Findings were reported today at TCT 2024, the annual scientific symposium of the Cardiovascular Research Foundation (CRF). TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. The results were also published simultaneously in the Journal of the American College of Cardiology.
Medical neurohormonal modulation and afterload reduction are key elements in the treatment of HFrEF. In patients with HFrEF and moderate AS, a complementary target for afterload reduction may be treatment of the AS. However, current guidelines recommend TAVR for symptomatic severe AS or for asymptomatic severe AS with left ventricular (LV) ejection fraction <50% but not for moderate AS.
The investigator-initiated, international, randomized controlled trial enrolled patients with NYHA class II-IV HFrEF (LV ejection fraction ≥20% and <50%) and moderate AS (aortic valve area >1.0 cm2 and ≤1.5 cm2) who were suitable for transfemoral TAVR with a balloon-expandable valve. From January 2017 to December 2022, 178 patients at 66 institutions in the United States, Netherlands and Austria 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 participants was 77 years, 20.8% were female and 55.6% were in NYHA class III or IV. The mean LV ejection fraction was 39%. During the study, 39% (n=35) of those in the medical therapy group progressed from moderate to severe AS.
The original study design required 600 patients (two groups of 300) with a primary endpoint analysis at one year. However, an updated protocol allowed for the use of the longest available follow-up data, justifying a reduced sample size of 300 patients (2 groups of 150). Due to funding limitations and slow enrollment, the Steering Committee decided to terminate enrollment by December 31, 2022, ensuring at least one year of follow-up for all participants.
The primary end point was the hierarchical occurrence of all-cause death, disabling stroke, disease-related hospitalizations, and HF equivalents, as well as the change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS). At one year, TAVR resulted in more wins driven by clinically meaningful improvement in quality of life compared with clinical AS surveillance [Win Ratio = 1.55 (1.04-2.31), p=0.032]. However, TAVR did not affect the primary composite endpoint at a median follow up of 23 months [Win Ratio = 1.31 (0.91-1.88), p=0.143]. In addition, MACCE [Hazard Ratio 0.83 (95% CI, 0.56-1.24, p=0.36)] and all-cause death [Hazard Ratio 0.98 (95% CI, 0.61-1.56, p=0.92)] were not significant between the two groups.
"Although TAVR for moderate aortic stenosis 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," said Nicolas M. Van Mieghem, MD, PhD, Professor and Clinical Director of Interventional Cardiology, Department of Cardiology, Cardiovascular Institute, Thoraxcenter Erasmus University Medical Center.
During the trial, more than 40 percent of the surveillance group underwent TAVR predominantly because of disease progression from moderate to severe aortic stenosis, which is more than we anticipated. The cardiac damage framework may identify a broader patient phenotype with moderate aortic stenosis that may benefit from upstream TAVR and is currently under investigation in other trials."
Nicolas M. Van Mieghem, MD, PhD, Professor and Clinical Director, Interventional Cardiology, Department of Cardiology, Cardiovascular Institute, Thoraxcenter Erasmus University Medical Center
The study was funded by Edwards Lifesciences.
Dr. Van Mieghem reported the following disclosures: institutional research grants from Abbott Vascular, Boston Scientific, Medtronic, Teleflex, PulseCath BV, Meril, Pie Medical and Edwards Lifesciences as well as consultancy/advisory fees from Abbott, Abiomed, Alleviant Medical Inc., AncorValve, Anteris, Approxima Srl, Bolt Medical, Boston Scientific, Luma Vision, Materialise, Medtronic, Pie Medical, Polares, PulseCath BV and Siemens.
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