What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure with reduced ejection fraction (HFrEF) (n=9133). Intervention: Moderate aortic stenosis vs. No aortic stenosis. Primary outcome: Composite of all-cause mortality and heart failure hospitalization (HR 1.24, 95% CI 1.04-1.49, p=0.01).

What question did this study set out to answer?

To assess clinical outcomes in patients with heart failure with reduced ejection fraction and moderate aortic stenosis compared to those with severe aortic stenosis or no aortic stenosis.

June 20, 2026Journal of the American College of CardiologyOpen Access

Impact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction

Q: What are the key findings of this study?

In patients with heart failure with reduced ejection fraction, moderate aortic stenosis was associated with an increased risk of heart failure hospitalization and mortality (HR 1.24) compared to no aortic stenosis.

Q: What does this research mean for the field?

In patients with heart failure with reduced ejection fraction, moderate aortic stenosis is associated with an increased risk of heart failure hospitalization and mortality (HR 1.24) compared to no aortic stenosis. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

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Key result

Moderate AS in HFrEF linked to ~24% higher risk of mortality and HF hospitalization.

HR 1.24
95% CI 1.04-1.49
P=0.01
n=9,133

Why the study?

Afterload from moderate aortic stenosis may contribute to adverse outcomes in patients with HFrEF, but its impact relative to no AS and severe AS was unclear.

Does moderate aortic stenosis increase the risk of heart failure hospitalization and mortality in patients with HFrEF compared to those without aortic stenosis?

Key Points

To assess clinical outcomes in patients with heart failure with reduced ejection fraction and moderate aortic stenosis compared to those with severe aortic stenosis or no aortic stenosis.
Retrospectively identified 9,133 patients with heart failure with reduced ejection fraction (LVEF <50%), including 374 with moderate aortic stenosis, 362 with severe aortic stenosis, and 8,412 without aortic stenosis.
Tracked the primary composite endpoint of heart failure hospitalization and all-cause mortality over a median follow-up of 3.1 years, utilizing multivariable adjustment and 1:1 propensity score matching.
The primary outcome occurred in 62.7% of patients with moderate aortic stenosis vs 45.9% with no aortic stenosis (P < 0.0001), showing rates similar to severe aortic stenosis (62.0% vs 62.7%; P = 0.68).
In the propensity-matched cohort, moderate aortic stenosis was independently associated with an elevated risk of the primary composite outcome (HR: 1.24; 95% CI: 1.04-1.49; P = 0.01) and fewer days alive outside of the hospital (P < 0.0001).
Aortic valve replacement was performed in 12.2% of moderate aortic stenosis patients and was associated with significantly improved survival (HR: 0.60; CI: 0.36-0.99; P < 0.05).

Study Design

Type

Cohort (n=9,133)

Multicenter

Structured PICO

Does moderate aortic stenosis increase the risk of heart failure hospitalization and mortality in patients with HFrEF compared to those without aortic stenosis?

Population

9,133 patients with heart failure with reduced ejection fraction (LVEF <50%) and varying degrees of aortic stenosis, followed for a median of 3.1 years.

Exposure

Moderate aortic stenosis (defined as an aortic valve area of 1.0 to 1.5 cm2)

Comparator

No aortic stenosis (negative control) and severe aortic stenosis (aortic valve area <1.0 cm2) (positive control). Propensity score matching (1:1) was used to compare the moderate AS group to the no AS group.

Outcome

Composite of heart failure hospitalization and all-cause mortalitycomposite

Main Result

Hazard Ratio: 1.24 (95% CI 1.04–1.49)

Absolute Event Rate: 64.4% vs 59.9%

p-value: p=0.01

In patients with HFrEF, the presence of moderate aortic stenosis is associated with significantly increased rates of heart failure hospitalization and mortality compared to those without aortic stenosis.

Limitations

Retrospective analysis design
Reliance on administrative claims-based data for comorbidities and heart failure hospitalization, subject to misclassification bias
Severity of aortic stenosis defined solely on aortic valve area without dobutamine stress echocardiography or calcium score
Total follow-up time was longer in patients without aortic stenosis
Aortic valve replacement was treated as a binary variable rather than a time-dependent variable
Potential residual confounders despite propensity score matching and multivariable adjustment
Retrospective study design
Single-center cohort

Discussion

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Key expert perspectives

Captured external expert commentary on this paper, strongest first. Original sources are linked where available.

SE Sammy ElmariahProfessor of Medicine, UCSF

“Of course, we all know that the underpinning of heart failure management in patients with reduced ejection universally depends on afterload reduction. It makes logical sense that patients with increased afterload related to moderate aortic stenosis may benefit from earlier intervention.”

University of California, San FranciscoNews Coverage

PGPhilippe GénéreuxInterventional cardiologist, Morristown Medical Center

“People will often say, 'It's only moderate AS,' but moderate AS is bad. When you look at the valves, they're very calcified, they're restricted. It puts an extra load, more pressure on the left ventricle. Even mild aortic stenosis can be seen as bad especially since it progresses so fast. To have mild or moderate AS is not the same as having no aortic stenosis at all. I think we need to reevaluate the spectrum of AS severity because we've been very complacent in the past.”

Atlantic Health System/Morristown Medical CenterNews Coverage

PSPaul SorajjaInterventional cardiologist, Minnesota Heart Institute

“We have clear evidence of an association with impaired survival, but a causative role for moderate aortic stenosis is currently lacking.”

Minnesota Heart Institute FoundationEditorial

Implication

Moderate AS identifies higher-risk HFrEF patients; hypothesis-generating for intervention trials before practice change.

Cite This Study

Khan et al. (2023) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=9,133). Moderate aortic stenosis vs. No aortic stenosis was evaluated on Composite of all-cause mortality and heart failure hospitalization (HR 1.24, 95% CI 1.04-1.49, p=0.01). In patients with heart failure with reduced ejection fraction, moderate aortic stenosis was associated with an increased risk of heart failure hospitalization and mortality (HR 1.24) compared to no aortic stenosis.

synapsesocial.com/papers/6a36af6485d7be32bde0d9e2 https://doi.org/10.1016/j.jacc.2023.01.032

Topics

HFrEF treatment Heart failure

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Impact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Key expert perspectives

Implication

Cite This Study

Topics

Impact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Key expert perspectives

Implication

Cite This Study

Also Consider

Topics

Also Consider