Prevalence and Prognostic Impact of Valve Area—Gradient Patterns in Patients ≥80 Years With Moderate-to-Severe Aortic Stenosis (from the Prospective BELFRAIL Study)

doi:10.1016/j.amjcard.2015.05.062

The American Journal of Cardiology

Volume 116, Issue 6, 15 September 2015, Pages 925-932

https://doi.org/10.1016/j.amjcard.2015.05.062 Get rights and content

Although degenerative aortic valve stenosis (AS) is common with increasing age, limited data exist regarding the prevalence and prognostic impact of its various valve area—gradient patterns in patients ≥80 years. To test this, echocardiograms were obtained in 542 randomly selected subjects aged ≥80 years recruited in the Belgium Cohort Study of the Very Elderly study (BFC80+). Subjects were divided into 3 groups: no or mild AS, moderate AS, and severe AS. Patients with severe AS were further stratified into those with high mean gradients (HG-AS) and those with paradoxically low mean gradients (LG-AS). Prevalence of moderate-to-severe AS was 14.7% and that of severe AS was 5.9%. In patients with severe AS, most (72%) exhibited paradoxical LG-AS. All patients with severe HG-AS were asymptomatic at the time of inclusion, whereas 48% of those with severe paradoxical LG-AS had significant symptoms. During follow-up, there were 2 aortic valve replacements and 230 deaths, of which 100 (43%) were of cardiovascular origin. Five-year overall survival rate was significantly worse in severe HG-AS than in any of the other groups (22 ± 14% vs 62 ± 2% in no or mild AS, 48 ± 7% in moderate AS, and 43 ± 10% in severe paradoxical LG-AS, p <0.01). Survival rate was similar among severe paradoxical LG-AS with and without low flow. In conclusion, in this large population-based sample of subjects ≥80 years, the prevalence of severe AS was 5.9%. Most of these subjects presented with the severe paradoxical LG-AS and a third of them were symptomatic. In this elderly community, severe HG-AS is a major determinant of prognosis, even in the absence of symptoms, whereas severe paradoxical LG-AS seems to behave similarly to moderate AS.

Section snippets

Methods

The BFC80+ study is a prospective, observational, population-based cohort study of subjects ≥80 years in 3 well-circumscribed areas of Belgium. The study design and characteristics of the cohort have been described in detail elsewhere.4, 5 From November 2, 2008, to September 15, 2009, 567 subjects were included in the BFC80 + study. Of these patients, 25 subjects were excluded from the present analysis, 11 because of lack of baseline echocardiographic data and 14 because of previous aortic

Results

The baseline clinical, hemodynamic, and echocardiographic characteristics of the study population are listed in Tables 1 and 2. Moderate-to-severe AS was found in 80 of 542 patients (14.7%), of whom 32 had severe AS (5.9%) and 48 had moderate AS (9.0%). In patients with severe AS, paradoxical LG-AS was more prevalent than HG-AS (23 of 32 vs 9 of 32). Compared with patients with no or mild AS, those with severe AS were older, more frequently experienced NYHA class III-IV symptoms, more often

Discussion

The present study found that, of patients ≥80 years, the prevalence of moderate-to-severe AS was 14.7% and that of severe AS, 5.9%. In patients with severe AS, the majority (72%) exhibited the paradoxical LG form of severe AS, whereas the remaining 28% presented with severe HG-AS. Interestingly, all the patients with severe HG-AS were asymptomatic at the time of inclusion into the study, which contrasted with the situation in patients with severe paradoxical LG-AS, who often presented with

Disclosures

The authors have no conflicts of interest to disclose.

References (30)

B. Vaes et al.
The prevalence of cardiac dysfunction and the correlation with poor functioning among the very elderly
Int J Cardiol
(2012)
M. Lindroos et al.
Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample
J Am Coll Cardiol
(1993)
B.F. Stewart et al.
Clinical factors associated with calcific aortic valve disease
J Am Coll Cardiol
(1997)
S.L. Lin et al.
Age-related changes in aortic valve with emphasis on the relation between pressure loading and thickened leaflets of the aortic valves
Int J Cardiol
(2005)
V.T. Nkomo et al.
Burden of valvular heart diseases: a population-based study
Lancet
(2006)
R.L. Osnabrugge et al.
Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study
J Am Coll Cardiol
(2013)
D. Leibowitz et al.
Prevalence and prognosis of aortic valve disease in subjects older than 85 years of age
Am J Cardiol
(2013)
M.A. Clavel et al.
Outcome of patients with aortic stenosis, small valve area, and low-flow, low-gradient despite preserved left ventricular ejection fraction
J Am Coll Cardiol
(2012)
P. Lancellotti et al.
Clinical outcome in asymptomatic severe aortic stenosis: insights from the new proposed aortic stenosis grading classification
J Am Coll Cardiol
(2012)
C. Tribouilloy et al.
Low-gradient, low-flow severe aortic stenosis with preserved left ventricular ejection fraction: characteristics, outcome, and implications for surgery
J Am Coll Cardiol
(2015)

S. Piérard et al.

Incidence, determinants, and prognostic impact of operative refusal or denial in octogenarians with severe aortic stenosis

Ann Thorac Surg

(2011)

P. Green et al.

The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis: a single-center experience

JACC Cardiovasc Interv

(2012)

Z. Hachicha et al.

Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival

Circulation

(2007)

H.M. Connolly et al.

Severe aortic stenosis with low transvalvular gradient and severe left ventricular dysfunction: result of aortic valve replacement in 52 patients

Circulation

(2000)

N. Jander et al.

Outcome of patients with low-gradient “severe” aortic stenosis and preserved ejection fraction

Circulation

(2011)

Cited by (16)

Low-Flow, Low-Gradient Severe Aortic Stenosis in patients with preserved or reduced ejection fraction: a systematic literature review.
2024, Current Problems in Cardiology
A systematic review of the literature was conducted to analyze the current evidence on low-flow, low-gradient severe aortic stenosis. This analysis aimed to differentiate between subgroups of patients with reduced and preserved left ventricular ejection fraction (LVEF).
After conducting a systematic literature review, 35 observational studies were included. Out of these, 28 were prospective and 7 retrospective. The studies that included a mortality risk stratification of low-flow, low-gradient aortic stenosis (LF- LG AS) with both preserved and reduced LVEF were reviewed.
The importance of considering multiple clinical and echocardiographic variables in diagnostic evaluation and therapeutic decision-making was highlighted.
LF- LG AS, in any of its subgroups, is a common and challenging valve lesion. A careful assessment of severity and, in specific scenarios, a thorough reclassification is important. More high-quality studies are required to more precisely define the classification and prognosis of this entity.
Natural history of moderate aortic stenosis and predictors for mortality: Systematic review and meta-analysis
2023, Journal of Cardiology
Although the current guidelines advocate imaging surveillance for moderate aortic stenosis (AS), recent studies suggest a worse prognosis associated with moderate AS than previously reported. Considering the recent paradigm shift in AS management, the risk/benefit profile of aortic valve replacement (AVR) for moderate AS needs to be re-evaluated. Herein, we conducted meta-analyses of natural history and risk predictors in patients with moderate AS. PubMed and EMBASE were searched through May 2022 to identify studies that investigated the natural history of patients with moderate AS. Meta-analyses with random effects model were conducted. Our analysis included 20 observational studies which enrolled a total of 11,114 patients with moderate AS. The rate of all-cause death was 11.0 [95 % confidence interval (CI), 7.6–14.4] per 100 patients per year. Surgical or transcatheter AVR occurred at a rate of 8.5 (95 % CI, 6.2–10.8; I², 98.9 %) per 100 patients per year. Occurrence of AVR during follow-up [hazard ratio (HR) (95 % CI) = 0.56 (0.42–0.75), p < 0.001] and early AVR for moderate AS [HR (95 % CI) = 0.47 (0.25–0.90), p = 0.02] were associated with significantly lower all-cause mortality, while left ventricular ejection fraction <50 % [HR (95 % CI) = 1.84 (1.33–2.57), p = 0.0003] and symptomatic status [HR (95 % CI) = 1.52 (1.32–1.75), p < 0.0001] were associated with increased all-cause mortality. Sex difference was not related to all-cause mortality. Our meta-analysis suggested that moderate AS was associated with high mortality, especially in low left ventricular systolic function or symptomatic patients. In addition, significant portion of the patients underwent AVR during follow-up.
Impact of Moderate Aortic Stenosis on Long-Term Clinical Outcomes: A Systematic Review and Meta-Analysis
2022, JACC: Cardiovascular Interventions
Citation Excerpt :
A total of 277,041 patients from 8 studies7,8,18,19,21,22,38,40 with a mean follow-up of 3.7 ± 1.7 years were included in the meta-analysis comparing the all-cause mortality of patients with no or mild versus moderate AS. A total of 13,848 patients from 11 studies6-8,18,19,21,24,25,27,28,41 with a mean follow-up of 3.8 ± 1.7 years were included in the meta-analysis comparing the all-cause mortality of patients with severe versus moderate AS. The rate of all-cause death was 9.0 (95% CI: 6.9 to 11.7; I2 = 97%) per 100 person-years (Figure 1A).
The clinical course of patients with moderate aortic stenosis (AS) remains incompletely defined.
This study sought to analyze the clinical course of moderate AS and compare it with other stages of the disease.
Multiple electronic databases were searched to identify studies on adult moderate AS. Random-effects models were used to derive pooled estimates. The primary endpoint was all-cause death. The secondary endpoints were cardiac death, heart failure, sudden death, and aortic valve replacement.
Among a total of 25 studies (12,143 moderate AS patients, 3.7 years of follow-up), pooled rates per 100 person-years were 9.0 (95% CI: 6.9 to 11.7) for all-cause death, 4.9 (95% CI: 3.1 to 7.5) for cardiac death, 3.9 (95% CI: 1.9 to 8.2) for heart failure, 1.1 (95% CI: 0.8 to 1.5) for sudden death, and 7.2 (95% CI: 4.3 to 12.2) for aortic valve replacement. Meta-regression analyses detected that diabetes (P = 0.019), coronary artery disease (P = 0.017), presence of symptoms (P < 0.001), and left ventricle (LV) dysfunction (P = 0.009) were associated with a significant impact on the overall estimate of all-cause death. All-cause mortality was higher in patients with reduced LV ejection fraction (<50%) than with normal LV ejection fraction: 16.5 (95% CI: 5.2 to 52.3) and 4.2 (95% CI: 1.4 to 12.8) per 100 person-years, respectively. Compared with moderate AS, the incidence rate difference of all-cause mortality was -3.9 (95% CI: -6.7 to -1.1) for no or mild AS and +2.2 (95% CI: +0.8 to +3.5) for severe AS patients.
Moderate AS appears to be associated with a mortality risk higher than no or mild AS but lower than severe AS, which increases in specific population subsets. The impact of early intervention in moderate AS patients having high-risk features deserves further investigation.
Integration of Flow-Gradient Patterns Into Clinical Decision Making for Patients With Suspected Severe Aortic Stenosis and Preserved LVEF: A Systematic Review of Evidence and Meta-Analysis
2016, JACC: Cardiovascular Imaging
Citation Excerpt :
Also, there are reports of LFLG SAS patients whose test results show an increase in transaortic gradients over time which is not consistent with the notion that LFLG SAS is the “burnt-out” stage of SAS (28). Other studies have suggested that LFLG SAS carries outcomes similar to moderate aortic stenosis (10,30). While our study showed a significant difference in the natural history of LG SAS based on the estimation of the SVI, a high degree of heterogeneity was observed in all analyses.
This study was designed to evaluate the evidence base for the 2014 American Heart Association/American College of Cardiology (AHA/ACC) guidelines for severe aortic stenosis (SAS) and preserved left ventricular ejection fraction by comparing the natural history of the disease in subgroups of low-gradient (LG) aortic stenosis patients with high-gradient (HG) patients.
The 2014 AHA/ACC valvular disease guidelines recommend estimation of stroke volume index by echocardiography in patients with suspected LG SAS and preserved left ventricular ejection fraction.
PubMed, Embase, and Scopus databases were searched for all studies that have compared the natural history of SAS with preserved ejection fraction in flow-gradient patterns. We studied the following 3 subgroups: HG, low-flow low-gradient (LFLG), and normal-flow low-gradient (NFLG). The random effects model was used to pool individual study results. The end-point was long-term all-cause mortality.
A total of 9 studies with 3,065 patients fulfilled the criteria. Compared to HG SAS, both LFLG and NFLG patients had a higher burden of comorbidities such as coronary artery disease and hypertension. Atrial fibrillation was more prevalent in LFLG patients. Moreover, end-diastolic volume index was smaller for LFLG patients and indexed aortic valve area was larger for NFLG patients. All-cause mortality was similar between HG and LFLG subgroups (relative risk: 1.07; 95% confidence interval: 0.83 to 1.38; p = 0.60), whereas patients with NFLG had a significantly lower all-cause mortality compared to the HG subgroup (relative risk: 0.64; 95% confidence interval: 0.47 to 0.86; p = 0.004).
Patients with LFLG SAS have similar outcomes compared to HG SAS but worse compared to NFLG SAS. These findings support estimating stroke volume index in patients with suspected LG SAS. All analyses revealed high heterogeneity and further high-quality studies are necessary.
Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis
2023, European Heart Journal Cardiovascular Imaging
Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits
2022, Frontiers in Cardiovascular Medicine

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Valvular Heart DiseasePrevalence and Prognostic Impact of Valve Area—Gradient Patterns in Patients ≥80 Years With Moderate-to-Severe Aortic Stenosis (from the Prospective BELFRAIL Study)

Section snippets

Methods

Results

Discussion

Disclosures

Int J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Int J Cardiol

Lancet

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Ann Thorac Surg

JACC Cardiovasc Interv

Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival

Circulation

Severe aortic stenosis with low transvalvular gradient and severe left ventricular dysfunction: result of aortic valve replacement in 52 patients

Circulation

Outcome of patients with low-gradient “severe” aortic stenosis and preserved ejection fraction

Circulation

Valvular Heart Disease
Prevalence and Prognostic Impact of Valve Area—Gradient Patterns in Patients ≥80 Years With Moderate-to-Severe Aortic Stenosis (from the Prospective BELFRAIL Study)