Dr. Bilal Çakır

Name of the Study: Transcatheter Aortic Valve Replacement in Patients with Systolic Heart Failure and Moderate Aortic Stenosis: The TAVR UNLOAD Trial

Published in Congress: TCT 2024

Link: https://www.tctmd.com/slide/transcatheter-aortic-valve-replacement-patients-systolic-heart-failure-and-moderate-aortic

Introduction:

In patients with heart failure with reduced ejection fraction (HFrEF), control of neurohormonal activation and reduction of cardiac afterload are the main elements of treatment. In patients with HFrEF and associated moderate aortic stenosis (AS), transcatheter aortic valve implantation (TAVI) to reduce afterload may be an adjunct to guideline directed medical therapy (GDMT).

Objective:

This study aimed to determine whether TAVI application provides additional clinical benefit to GDMT in cases of moderate AS accompanied by HFrEF.

Methods:

In an open-label, randomized controlled, internationally conducted study, 178 symptomatic HFrEF patients with moderate AS receiving GDMT were randomized into TAVI (n=89) and clinical aortic stenosis surveillance (CASS) (n=89) arms. All patients included in the study were planned to be suitable for balloon expandable valve implantation via a transfemoral approach, and in the CASS arm, TAVI was applied in case of progression to severe AS during follow-up. In this superiority trial with a median follow-up of 23 months, the primary endpoint was the hierarchical occurence of all-cause death, disabling stroke, AS/heart failure hospitalization, and change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score. The Finkelstein Schoenfeld method was used in statistical analysis and the results were presented using the win ratio.

Results:

The mean age of the study population was 77, and the proportion of female patients was 20.8%. When patients were classified according to their functional capacity, 43.3% of patients were in NYHA-?, 52.2% in NYHA-? and 3.4% in NYHA-?. TAVI was performed in 38 patients (43%) in the CASS arm (35 patients had progression to severe AS during follow-up) at a median of 12 months after randomization. The TAVI arm resulted in a win in 47.6% of couples compared with 36.6% in the CASS arm, resulting in a win ratio of 1.31 (95% CI: 0.91–1.88; P = 0.14). At 1 year, a greater improvement in the KCCQ global summary score was observed in the TAVI arm compared with the CASS arm (12.8 ± 21.9 points vs 3.2 ± 22.8 points; P = 0.018).

Conclusions: 

Transcatheter aortic valve implantation is not superior to CASS in primary hierarchical composite endpoint in patients with HFrEF and moderate AS. In addition, TAVI application is reliable in this patient group and can provide significant improvement in quality of life.

Comment:

The TAVR UNLOAD Trial is the first randomized controlled trial to evaluate TAVI for moderate AS in patients with HFrEF under GDMT. Although TAVI appears to be a reliable procedure that improves quality of life in patients with moderate AS and HFrEF, no significant difference was found between the TAVI and CASS arms in terms of the primary hierarchical composite endpoint at the end of a median follow-up period of 23 months. However, the relatively slow progression of the study (patient recruitment occurred between June 2017 and December 2022) and the small sample size reduce the power of the study. In addition, the need for TAVI during follow-up of patients in the CASS arm was higher than expected (38/89), which negatively affected the comparison between the groups. From this perspective, the findings are more of a hypothesis-generating nature. Results from the PROGRESS and EXPAND TAVR ? studies will help identify phenotypes of patients with moderate AS who will benefit from upstream TAVI.