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Transcatheter Aortic Valve Replacement in Patients With Systolic Heart Failure and Moderate Aortic Stenosis
Nicolas M. Van MieghemSammy ElmariahErnest SpitzerPhilippe PîbarotTamim NazifJ. J. BaxRebecca T. HahnAlexandra PopmaOri Ben‐YehudaFaouzi KallelBjörn RedforsMichael L. ChuangMaria AluWietze LindeboomDhaval KolteFiras ZahrSusheel KodaliJustin A StroteRenicus S. HermanidesDavid J. CohenJan G.P. TijssenMartin B. Leon
Key result
TAVR was not superior to clinical surveillance for the primary hierarchical composite endpoint in patients with HFrEF and moderate aortic stenosis (win ratio 1.31; 95% CI: 0.91-1.88; P = 0.14).
Why the study?
In patients with HFrEF on GDMT and concomitant moderate AS, it was unknown whether TAVR provides additional clinical benefit.
Does preemptive TAVR improve a hierarchical composite of clinical outcomes and quality of life in patients with HFrEF and moderate AS compared to clinical surveillance?
Key Points
- To determine whether early transcatheter aortic valve replacement improves clinical outcomes compared with active surveillance in patients with systolic heart failure and moderate aortic stenosis on guideline-directed medical therapy.
- International, randomized controlled trial assigning 178 patients with HFrEF and moderate aortic stenosis 1:1 to transfemoral TAVR (n = 89) or clinical aortic stenosis surveillance (CASS, n = 89).
- Patients in the surveillance arm underwent aortic valve replacement only after documented progression to severe aortic stenosis, with a median overall follow-up of 23 months (IQR: 12-33 months).
- The primary endpoint was a hierarchical composite analyzed by win ratio including all-cause death, disabling stroke, disease-related hospitalizations or heart failure equivalents, and change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score.
- TAVR was not superior to surveillance for the primary composite endpoint, yielding a win ratio of 1.31 (95% CI: 0.91-1.88; P = 0.14), with wins in 47.6% of pairs for TAVR versus 36.6% for surveillance.
- At 1 year, TAVR resulted in significantly greater improvement in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score compared with surveillance (12.8 ± 21.9 vs 3.2 ± 22.8 points; P = 0.018).
- In the surveillance arm, 38 patients (43%) underwent TAVR at a median of 12 months after randomization, 35 of whom had progressed to severe stenosis.
Study Design
Type
RCT (n=178)
Blinding
Open-label
Randomization
1:1
Multicenter
Yes
Structured PICO
Does preemptive TAVR improve a hierarchical composite of clinical outcomes and quality of life in patients with HFrEF and moderate AS compared to clinical surveillance?
P
Population
178 older adults (mean age 77.4 years, 20.8% female) with symptomatic HFrEF (LVEF 20%-50%) on stable guideline-directed medical therapy and concomitant moderate aortic stenosis, followed for a median of 23 months.
I
Intervention
Transfemoral transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve added to guideline-directed medical therapy (GDMT).
C
Comparator
Clinical aortic stenosis surveillance (CASS) with aortic valve replacement upon progression to severe AS, on top of guideline-directed medical therapy (GDMT).
O
Outcome
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.composite
Main Result
Effect estimate: Win ratio 1.31 (95% CI 0.91-1.88)
Absolute Event Rate: 47.6% vs 36.3%
p-value: p=0.14
In patients with HFrEF and moderate AS, preemptive TAVR did not significantly improve a hierarchical composite of clinical outcomes and quality of life compared to routine surveillance, though it did provide quality-of-life benefits at 1 year.
Limitations
- Multiple study design changes and underpowered sample size (<70% power) due to slow enrollment and funding constraints
- Open-label design may introduce placebo effects in quality-of-life assessments
- High rate of progression to severe AS and crossover to TAVR (43%) in the clinical surveillance group may have attenuated intergroup comparisons
- Limited adoption of newer heart failure medications (sacubitril/valsartan and SGLT2 inhibitors) during the trial period
- Relatively small sample size precluded heterogeneity testing
Ask about this paper
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“We should not change the current guidelines. I think it is worthwhile to wait for moderate aortic stenosis to become severe in symptomatic heart failure patients before you expose these patients to a TAVR. That said, in patients who have recurring symptoms that are difficult to control medically, those might be good candidates for a preemptive TAVR. So it’s a selected group of patients.”
“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. 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.”
JZJeffrey ZimmetAssociate Professor of Medicine, UCSF; Cardiology Director, SFVA
“On the face of it, these results confirm that we are not doing harm to our HFrEF patients by following current guidelines and waiting until AS is severe before proceeding to TAVR. Thus, guidelines are unlikely to change for this population based on this report. That said, given the relative safety of the procedure, there certainly is room for individualized management, with earlier TAVR in a limited subset of patients who continue to have recurrent heart failure symptoms despite optimal guideline-directed medical therapy.”
Implication
TAVR is not superior to surveillance in HFrEF with moderate AS; challenges early intervention and leaves open questions for specific phenotypes.
Abstract
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.
Discussion
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Cite This Study
Mieghem et al. (2024) conducted an RCT in Systolic heart failure (HFrEF) and moderate aortic stenosis (n=178). Transfemoral transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve (SAPIEN 3) vs. Clinical aortic stenosis surveillance (CASS) with AVR upon progression to severe AS was evaluated on Hierarchical occurrence of all-cause death, disabling stroke, disease-related hospitalizations and heart failure equivalents, and change from baseline in the KCCQ Overall Summary Score (Win ratio 1.31, 95% CI 0.91-1.88, p=0.14). TAVR was not superior to clinical surveillance for the primary hierarchical composite endpoint in patients with HFrEF and moderate aortic stenosis (win ratio 1.31; 95% CI: 0.91-1.88; P = 0.14).