Clinical Research
Valvular Heart Disease
Low-Gradient Aortic Valve Stenosis: Myocardial Fibrosis and Its Influence on Function and Outcome

https://doi.org/10.1016/j.jacc.2011.02.059Get rights and content
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Objectives

This prospective cohort study in patients with aortic stenosis (AS) aimed to identify surrogates of myocardial fibrosis that are easy to derive in clinical practice, allow the differentiation of low-gradient severe AS from moderate AS, and have an impact on clinical outcome.

Background

In patients with symptomatic aortic AS, a characteristic subgroup (i.e., up to one-third) exhibits severe AS with a concomitant low mean valve gradient either with preserved or reduced ejection fraction (EF). It is hypothesized that these patients tend to have an advanced stage of myocardial fibrosis and poor clinical outcome.

Methods

Eighty-six patients with moderate or severe AS were examined by echocardiography including conventional aortic valve assessment, mitral ring displacement, and strain-rate imaging. Replacement fibrosis was quantified by late-enhancement magnetic resonance imaging. Biopsy samples were taken from patients with severe AS (n = 69) at aortic valve replacement. All patients were followed for 9 months.

Results

Patients were divided into 4 groups according to aortic valve area (<1.0 cm2), mean valve gradient ≥40 mm Hg, and EF (<50%): group 1, moderate AS (n = 17); group 2, severe AS/high gradient (n = 49); group 3, severe AS/low gradient/preserved EF (n = 11); and group 4, severe AS/low gradient/decreased EF (n = 9). At baseline, a significant decrease in mitral ring displacement and systolic strain rate was detected in patients with low-gradient AS. In low-gradient groups, a higher degree of interstitial fibrosis in biopsy samples and more late-enhancement magnetic resonance imaging segments were observed. A close inverse correlation was found between interstitial fibrosis and mitral ring displacement (r = −0.79, p < 0.0001). Clinical outcome was best for patients in group 1, whereas mortality risk increased substantially in groups 2 through 4.

Conclusions

In severe AS, a low gradient is associated with a higher degree of fibrosis, decreased longitudinal function, and poorer clinical outcome despite preserved EF. Mitral ring displacement differentiates between moderate AS and low-gradient/severe AS with preserved EF.

Key Words

aortic stenosis
aortic valve
low gradient
myocardial fibrosis
myocardial function

Abbreviations and Acronyms

AS
aortic stenosis
AUROC
area under the receiver-operator characteristic curve
AVA
aortic valve area
AVR
aortic valve replacement
CI
confidence interval
cMRI
cardiac magnetic resonance imaging
EF
ejection fraction
LE
late enhancement
LV
left ventricular
NT-proBNP
N-terminal pro–B-type natriuretic peptide
NYHA
New York Heart Association
OR
odds ratio
PIIINP
procollagen type III amino terminal peptide

Cited by (0)

This work was supported by grants from the Bundesministerium für Bildung und Forschung (BMBF01 EO1004). The authors have reported that they have no relationships to disclose.