Echocardiographic evaluation of Aortic valve stenosis (AS) severity relies on aortic valve area and peak jet velocity. In pursuit of improving accuracy, the transaortic flow rate (FR), defined as the ratio of stroke volume to systolic ejection time, has been introduced. However, its prognostic value in AS patients remains a matter of controversy. This study aims to systematically review the predictive value of FR in AS patients and provide quantitative pooled analysis results where applicable. A systematic search was conducted for observational studies on AS patients published up to July 31, 2025. Studies were included if they assessed the clinical prognostic utility of FR with at least 3 months of follow-up. Pooled estimates and 95% CI for FR’s hazard ratio (HR) in each binary outcome were calculated using a random effects model. Twenty-one studies with 10,895 patients underwent descriptive analysis, and 19 eligible studies were included in the meta-analysis. For predicting all-cause mortality, the pooled HR for low FR measured at rest (cut-off value 200–210 mL/s) was 1.31 (95% CI: 1.03–1.60, I 2: 66%, p < 0.05). For FR measured during stress echocardiography (cut-off value 250 mL/s), the pooled HR was higher at 1.58 (95% CI: 1.20–1.96, I 2: 0%, p < 0.05). However, data in stress echocardiography have been drawn from a smaller number of studies compared to rest FR assessment, and validation in larger studies is warranted. Additionally, every 100 mL/s increase in FR, either at rest or stress, significantly reduced all-cause mortality. In Conclusion, FR is a prognostic marker for all-cause mortality and adverse composite outcomes in AS patients, indicating its potential for risk stratification. Incorporating FR into clinical assessments could help personalize follow-up and monitoring strategies.
Systematic Review Registration: PROSPERO (registration number: CRD42023404048).
Aortic valve stenosis (AS) is an active progressive valvular disease, with its prevalence closely linked to the aging of the population. , Despite significant advancements in AS treatment, mortality has risen in recent years by 138%. Furthermore, an extensive analysis of real-world data on a U.S. population with AS revealed a considerably higher mortality risk (13.5%–44.9%) associated with all types of untreated AS compared to the non-AS population.
Echocardiography plays a pivotal role in the diagnosis and evaluation of AS, serving as the initial step in noninvasive imaging for suspected patients. Traditionally, AS severity has been classified based on echocardiographic parameters, including aortic valve area (AVA), and 2 flow-dependent factors, namely peak jet velocity, and mean transaortic pressure gradient (MPG). Severe AS is defined as AVA < 1.0 cm 2 and a MPG ≥ 40 mm Hg or a peak jet velocity ≥ 4 m/s. Classifying the severity of AS is straightforward when all 3 measurements align. However, the process becomes more complicated when there are discrepancies. Approximately one-third of AS patients have an AVA of < 1 cm², along with 2 other factors that fall below the threshold for severe AS, a condition known as low-flow, low-gradient AS. This discordance has posed challenges for AS classification in recent years.
The Stroke Volume Index (SVI), which measures the stroke volume relative to body surface area (BSA), is a common metric in echocardiography for evaluating flow status in AS. First described by Hachicha et al., in patients with severe AS, an SVI below 35 mL/m² defines low-flow states and has been recognized as an important predictor of mortality after transcatheter aortic valve implantation (TAVI). , SVI is basically a measure of blood volume, whereas flow addresses the volume of blood passing through the valve over a given time period. In pursuit of a more accurate estimation of AS severity, the transaortic flow rate (FR), representing the ratio of stroke volume to systolic ejection time, has been introduced. FR, influenced by both time and volume, offers a more precise reflection of hemodynamic consequence and the blood flow burden on the AVA compared to SVI. , With Multiple recent studies focusing on FR in AS patients, FR has emerged as a prognostic factor for survival across various AS types, from asymptomatic to low-gradient severe AS and after aortic valve intervention, including TAVI. ,,,,
Furthermore, it is suggested that the AVA measured under low flow rates may not be an accurate prognostic and diagnostic marker for AS, highlighting the importance of routinely calculating FR in AS patients.
From the increasing sound of FR, we chose to systematically review its prognostic value in patients with varying degrees of AS and, where applicable, present quantitative pooled analysis results.
Methods
Study design
The current investigation was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA-NMA). The protocol of study was registered prospectively in PROSPERO (registration ID: CRD42023404048).
Systematic search
A primary systematic search was carried out by 3 independent investigators (MR.H, H.M., and S.S.) using PubMed, Cochrane, Web of Science, Scopus, and Embase databases to identify potentially eligible retrospective/prospective observational articles from inception to July 31, 2025.
Mesh Terms-Key words in our search strategy included (“Transaortic Flow Rate” OR “Transvalvular Flow Rate” OR “Flow Rate” OR “flow*”) AND (“Prognos*” OR “Prognostic” OR “Prognosis” OR “Outcome” OR “Mortality” OR “Hospital*” OR “Hospitalization” OR “Hospitalisation” OR “Major Advanced Cardiac Events” OR “MACE”) AND (“Aortic valve stenosis” OR “Aortic stenosis”). The comprehensive search strategy in different databases is provided in Table S1 . To ensure saturation, a manual reference cross-check of included articles was conducted. In addition, key journals, conference proceedings, trial registers, and internet resources were searched to identify studies potentially missed by the database search.
Thereafter, all identified studies were collected in the Endnote reference management tool (Clarivate, Version 21). Duplicate papers were first identified automatically by a prompt in Endnote; Subsequently, a manual screening was employed (by MR.H.) to further remove any remaining duplicates.
Title-abstract screening
The identified articles were divided between 2 reviewers (S.S. and F.CH.), who independently conducted an initial screening of titles and abstracts for their assigned portions. Afterward, the reviewers swapped portions and cross-checked each other’s work. Any discrepancies were resolved through discussion to reach a consensus. If consensus could not be achieved, a senior reviewer (H.M.) made the final decision.
Selection criteria
The inclusion criteria were as follows: (1) transaortic FR reported in patients diagnosed with any degree of AS; (2) clinical outcome data (all-cause mortality, cardiovascular mortality, major adverse cardiac events, hospitalization, and symptom onset) assessed based on FR results with a follow-up duration of at least 3 months; (3) available hazard ratio (HR) and 95% confidence interval (CI) for retrieval; and (4) adequate data for qualitative or quantitative analysis.
The exclusion criteria were: (1) nonhuman studies, and (2) studies using nonoriginal methodologies (including case reports, case series, letters to editors without original data, reviews, meta-analyses, and abstracts).
The full texts of the shortlisted studies were retrieved, further assessed, and thoroughly reviewed by MR.H. and H.M. to ensure they met the inclusion and exclusion criteria.
Data extraction and quality assessment
Four investigators (P.J., M.A., M.S., and MR.H.) were involved in data extraction and quality assessment for the included studies. The gathered data included the surname of the first author, the country of study, year of publication, study design, population characteristics (such as sample size, severity of AS, and symptom status), details of FR measurement, outcomes, follow-up period, and clinical and echocardiographic parameters. The qualitative analysis of the included studies was conducted using the Newcastle-Ottawa Scale. The quality assessment evaluated 3 main areas: the selection of study groups (0–4 points), the comparability of these groups (0 to 2 points), and the confirmation of the outcome of interest (0–3 points). Studies scoring 7 points or higher were classified as high-quality articles. Data entry accuracy was rechecked by the senior author (H.M.).
Outcome
The primary outcome was all-cause mortality. The secondary outcome was defined as a composite endpoint of mortality (all-cause or cardiovascular) combined with heart failure hospitalization or the onset of new AS-related symptoms.
Statistical analysis
Descriptive analysis
A descriptive analysis was initially performed to characterize the included studies and the clinical and demographic data of the participants. Categorical variables were expressed as frequencies and percentages, while continuous variables were presented as means with standard deviations or as medians.
Meta-analysis and forest plots
The HRs and their corresponding 95% CIs were extracted from the studies for a meta-analysis of binary outcomes. A random-effects model was employed to pool the reported HRs.
Two distinct pooled analyses of HRs were conducted based on the manner in which FR was reported. The “Categorized FR group” included studies that used a defined cut-off point for FR to report HRs. In contrast, the “Quantitative FR group” comprised studies that reported HRs based on per-unit changes in FR (e.g., 1 mL/s, 10 mL/s, or 100 mL/s). In the Quantitative FR group, before aggregating HRs, if needed, HRs got standardized and converted to a common unit (FR per 1 mL/s, 10 mL/s, or 100 mL/s), using the reciprocal and logarithmic statistics methodology. Additionally, another standardization of HR was applied for quantitative FR studies that reported HRs for per-unit increases or decreases in FR. These were adjusted to a uniform basis, reflecting HR per unit increase. Furthermore, if needed, 2 independent HRs in a study were combined using a fixed-effect inverse-variance meta-analysis of log-transformed estimates, with standard errors derived from reported 95% confidence intervals.
Given that FR was measured during either resting echocardiography or stress echocardiography (using dobutamine or exercise), separate effect models were used to pool the HRs. Therefore, 4 effect models were considered for each outcome: (1) categorized resting FR, (2) categorized stress FR, (3) quantitative resting FR, and (4) quantitative stress FR.
Meta-regression and subgroup analyses
In the presence of significant heterogeneity, meta-regression and subgroup analyses were performed. Factors identified by the expert echocardiologist (H.M.)—such as AS severity, pressure gradients, left ventricular ejection fraction (LVEF), SVI, and patient symptoms—served as primary delineators for subgroup analysis. Additionally, unadjusted factors like population size and follow-up duration were included in meta-regression to identify sources of heterogeneity.
Publication bias and sensitivity analysis
Publication bias was assessed using funnel plots, Egger’s test, and Peter’s test. In addition, Duval and Tweedie’s trim and fill method was applied to evaluate the potential impact of missing studies on the pooled results. A leave-one-out sensitivity analysis was conducted to gauge the robustness of the findings by evaluating the impact of excluding each individual study.
All statistical analyses were conducted using the meta-for and meta-R packages in R version 3.5.3 (R Foundation for Statistical Computing, Vienna, Austria), with a 2-tailed significance level set at p < 0.05.
Results
Publications selection process
A comprehensive search across 5 databases—PubMed, Cochrane, Web of Science, Scopus, and Embase—followed by the removal of duplicates through automated EndNote processes and manual review, resulted in 4247 articles being available for title and abstract screening. Out of these, 157 articles were selected for full-text retrieval. Despite significant efforts to reach out to the corresponding authors of 8 papers, they were ultimately excluded from the systematic review due to the unavailability of the full text. After a careful review of 149 full-text papers, 19 were found to meet the inclusion criteria for data extraction. Additionally, a manual search of additional sources identified 3 more relevant records. A total of 22 studies were included in the systematic review, with 19 of these studies incorporated into the quantitative analysis. The screening flow diagram is depicted in Figure 1 .
PRISMA flow diagram for systematic Review .
Descriptive analysis of included studies
A total of 10,895 AS patients from 22 studies were enrolled. The average age of the patients was 76.35 years, with 58.05% being men. The follow-up period varied between 9.1 and 51.6 months. Tables 1 and 2 summarize the descriptive and clinical data from included studies. Of these, 10 utilized a prospective cohort design, and 9 were conducted in multicenter settings. With respect to transaortic FR measurement, 17 studies provided data on FR during rest echocardiography. Three studies included measurements both at rest and under stress (induced by dobutamine or exercise), while 2 others reported FR only during stress echocardiography. Additionally, out of these 22 studies, 10 reported FR as a categorical variable, 7 provided quantitative FR data, and 5 included both categorical and quantitative FR measurements. Hypertension was the most common comorbidity reported, affecting 59.07% of the patients.
Table 1
Descriptive data of included studies in meta-analysis
| Population characteristics | Intervention (FR measurement) and Comparison | Outcome of interest | Follow-up | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Author | Country | Study design | Sample Size (Number) | Severity of AS | Symptoms status at the start of the study | AV intervention at the beginning of study as an inclusion criterion | Type of FR measurement |
Type of FR
comparison |
Cut-off point (mL/s) | Follow-up months (mean ± SD) | Withdrawal rate | |
| Springhetti et al. | Italy |
Retrospective
multicentric |
292 | 292 (100%) Moderate |
292 (100%)
Both symptomatic & asymptomatic |
No | Resting FR | Categorized | 218 | Composite endpoint of all-cause mortality and HF hospitalization | 19.2 ± 10.2 | NA |
| Hungerford et al. | Australia | prospective multicentric | 323 | 323 (100%) Severe | 323 (100%) Symptomatic |
Yes
(Pre-AVI FR comparison) |
Resting FR | Categorized | 210 | All-cause mortality | 36 | NA |
| Bar Gil et al. | Israel | Retrospective cohort, Monocentric | 824 | 330 (40%) Moderate, 494 (60%) Severe |
824 (100%)
Both symptomatic & asymptomatic |
No | Resting FR | Quantitative | NA | All-cause mortality, Surgical AVR, transcatheter AVI, CHF | 41.4 ± 19.92 | NA |
| Onishi et al. | Japan | Retrospective cohort, Monocentric | 100 | 100 (100%) Severe |
100 (100%)
Both symptomatic & asymptomatic |
No | Both Rest and stress FR (Dobutamine) | Both Categorized and Quantitative | 200 | Composite endpoint of all-cause mortality and HF hospitalization | 36 ± 37.8 | NA |
| Santos-Ferreira et al. | Portugal | Retrospective cohort, Monocentric | 489 | 489 (100%) Severe |
489 (100%)
Both symptomatic & asymptomatic |
Yes
(Pre-AVI comparison) |
Resting FR | Categorized | 200 | All-cause mortality | 60 | NA |
| Gallone et al. | Italy | Prospective cohort, multicentric | 731 | 731 (100%) Severe | 731 (100%) Symptomatic |
Yes
(Pre-AVI FR & Recovered/persistently low post-AVI FR in low Pre-AVI FR patients) |
Resting FR | Categorized | 200 |
Primary outcome:
All-cause mortality
Secondary outcome: Cardiovascular mortality |
15.6 ± 7.42 | NA |
| Patel et al. | UK | Retrospective cohort, Monocentric | 292 | 292 (100%) Severe |
292 (100%)
Symptomatic |
No | Resting FR | Quantitative | NA |
All-cause mortality
(OR reported instead of HR) |
28.8 ± 16.8 | NA |
| Alsidawi et al. | USA |
Prospective cohort,
Monocentric |
1541 | 1541 (100%) Severe |
1541 (100%)
Not specified |
No | Resting FR | Quantitative | NA | All-cause mortality | 24.8 ± 32 | NA |
| Rusinaru et al. | France & Belgium | Prospective cohort, Multicentric | 643 | 643 (100%) Severe | 477 (74.2%) Symptomatic | No | Resting FR | Quantitative | NA | All-cause mortality | 38.7 ± 36.5 | 5% |
| Saeed et al. | UK | Prospective cohort, Multicentric | 1564 |
1564 (100%)
Severe |
1564 (100%) Symptomatic | No | Resting FR | Both Categorized and Quantitative | 200 | All-cause mortality in those who went under AVI at follow up | 35 ± 22 | Follow-up was completed in all patients |
| Saeed et al. | UK | Retrospective cohort, Monocentric | 324 |
99 (30.6%) Moderate,
225 (69.4%) Severe |
324 (100%) Asymptomatic | No | Resting FR | Categorized | 200 |
Composite
endpoint of all-cause mortality and AVR |
23.7 ± 23.8 | 3 (0.92%) |
| Schwartzenberg et al. | Israel |
Retrospective cohort,
Mono-centric |
168 | 21 (12.5%) Moderate, 147 (87.5%) severe |
168 (100%)
Both symptomatic & asymptomatic |
No | Resting FR | Categorized | 210 | All-cause mortality | 9.1 ± 10.1 | NA |
| Sen et al. | Australia |
Retrospective cohort,
Monocentric |
621 | 621 (100%) Severe |
621 (100%)
Both symptomatic & asymptomatic |
No | Resting FR | Categorized | 200 |
Primary outcome
: composite endpoint of all-cause mortality, HF hospitalization, and aortic valvular interventions
Secondary outcomes: Individual components of the composite outcomes (All-cause mortality and HF hospitalization) |
11.6 (Median) | NA |
| Vriz et al. | Italy |
Prospective cohort,
Monocentric |
133 | 133 (100%) Moderate and severe (sub group was not specified) |
133 (100%)
Both symptomatic & asymptomatic |
No | Resting FR | Quantitative | NA | All-cause mortality | 51.6 ± 39.4 | Follow-up was completed in all patients |
| Wilde et al. | Germany | Retrospective cohort, Multicentric | 219 | 219 (100%) Severe | 219 (100%) Symptomatic |
Yes
(Pre-AVI FR comparison) |
Resting FR | Quantitative | NA |
Primary outcome ||: 1-year mortality
Secondary outcome ||: periprocedural complication, 30-day and mid-term (3 and 5 years) mortality |
24 ± 23.28 | NA |
| Vamvakidou et al. | Canada, Europe, USA, and UK | Prospective cohort, Multicentric | 287 | 287 (100%) Severe | 282 (98.3%) Symptomatic, 5(1.7%) Asymptomatic | No |
Stress FR
(Dobutamine test) |
Both Categorized and Quantitative | 210 | All-cause mortality | 24 ± 30 | NA |
| Hirasawa et al. | Japan | Retrospective cohort, Monocentric | 99 |
53 (53%) Moderate,
46 (47%) Severe |
99 (100%) Asymptomatic | No |
Both rest and stress FR
(Exercise test) |
Both Categorized and Quantitative |
270
(for stress echo) |
Composite
endpoint defined as cardiovascular death and new onset of AS-related symptoms |
14 ± 11 | NA |
| Gu et al. | UK | Retrospective cohort, Monocentric | 218 |
73 (33.5%) Moderate,
49 (22.5%) Severe, 96 (44.0%) Discordant |
218 (100%) Asymptomatic | No | Resting FR | Categorized | 200 | – Primary outcome: Composite endpoint defined as aortic valve Intervention, hospitalization for heart failure, and all-cause
Mortality. – Secondary outcome: All-cause mortality |
35.2 ± 22.7 | Follow-up was completed in all patients |
| Vamvakidou et al. | UK | Retrospective cohort, Monocentric | 218 | 218 (100%) Severe | 218 (100%) Symptomatic |
Yes
(Pre-AVI FR comparison) |
Resting FR | Categorized | 200 | All-cause mortality | 46.8 ± 21 | NA |
| Saeed et al. | Norway | Prospective cohort, Multicentric | 1,661 | 476 (28%) inconsistently graded severe AS, 1194(72%) consistently graded AS | 1661 (100%) Asymptomatic | No | Resting FR | Both Categorized and Quantitative | 200 | – Cardiovascular death
– All-cause mortality |
51.6 | NA |
| Bartko et al. | Austria |
Prospective cohort,
Mono centric |
47 | 47 (100%) Both severe and nonsevere |
47 (100%)
Both symptomatic & asymptomatic |
No | Both Rest and stress FR (Dobutamine) | Quantitative | NA | All-cause mortality | 33.3 ± 6.83 | 15 (24.19%) |
| Clavel et al. | Canada |
Prospective cohort,
Multicentric |
101 | 79 (78%) severe, 22 (22%) nonsevere |
79 (78%)
Both symptomatic & asymptomatic |
No | Stress FR (Dobutamine) | Categorized | 250 | All-cause mortality | 20 ± 15 | NA |
Abbreviations: AS = aortic stenosis; EF = ejection fraction; SD = standard deviation; AV = aortic valve; FR = flow rate; NA = not applicable; AVR = aortic valve replacement; AVI = aortic valve intervention.
Table 2
Clinical characteristics of patients
| Author | Age (years) | Men | Body surface Area (m 2) | BMI (Kg/m2) | Smoking | Comorbidities | |||
|---|---|---|---|---|---|---|---|---|---|
| HTN | DM | Dyslipidemia | CKD | ||||||
| Springhetti et al. | 80.3 ± 9.1 | 161 (55.1%) | NA | 26.6 ± 5.3 | 67 (22.9%) | 239 (81.9%) | 78 (26.7%) | 152 (52.1%) | NA |
| Hungerford et al. | 82 ± 8 | 183 (57%) | 1.82 ± 0.29 | 23 ± 9 | 82 (25%) | 195 (60%) | 9 (3%) | NA | 45 (14%) |
| Bar Gil et al. | 74.7± 13 | 420 (51.0%) | 1.78 ± 0.2 | 28.11 ± 4.47 | 112 (13.6%) | 554 (67.2%) | 353 (42.8%) | 523 (63.4%) | 89 (10.8%) |
| Onishi et al. | 79.5 ± 7.3 | 45 (45%) | 1.54 ± 0.18 | 23.4 ± 3.5 | 42 (42%) | 75 (75%) | 42 (42%) | 68 (68%) | 74 (74%) |
| Santos-Ferreira et al. | 81 (76 to 86) | 236 (48%) | 1.75 (1.64 to 1.87) | 26.8 (24.2 to 29.8) | NA | 360 (83%) | 185 (38%) | 314 (73%) | NA |
| Gallone et al. | 82 ± 6 | 526 (53.7%) | 2 | NA | 31 (3.8%) | 810 (84%) | 296 (30.7%) | 529 (61.7%) | 370 (42.9%) |
| Patel et al. | 83.75 ± 1.5 | 156 (54.1%) | NA | NA | NA | 214 (73.3%) | 77 (26.4%) | NA | 173 (59.4%) |
| Alsidawi et al. | 76 ± 11 | 816 (53%) | 1.8 ± 0.2 | NA | NA | 889 (57.6%) | 425 (27.5%) | 826 (53.6%) | 241 (15.7%) |
| Rusinaru et al. | 81.0 (75.0 to 86.4) | 238 (37.0%) | 1.78 ± 0.22 | 25.9 (22.9 to 29.5) | NA | 486 (75.6%) | 208 (32.3%) | NA | 167 (26.0%) |
| Saeed et al. | 76 ± 13 | 798 (51%) | 1.78 ± 0.23 | NA | 123 (7.86%) | 837 (53.51%) | 358 (22.9%) | 587 (37.53%) | 413 (26.40%) |
| Saeed et al. | 69 ± 13 | 198 (61%) | 1.88 ± 0.21 | 28.44 ± 5.41 | 126 (38.88%) | 242 (74.69%) | 67 (20.67%) | 207 (63.88%) | NA |
| Schwartzenberg et al. | 80 ± 4 | 78 (46.4%) | 1.8 ± 0.18 | NA | NA | 147 (87.5%) | 70 (41.7%) | 134 (84.8%) | 62 (36.9%) |
| Sen et al. | 76.4 ± 11.2 | 351 (57%) | NA | NA | NA | 415 (67%) | 237 (38%) | NA | 158 (25%) |
| Vriz et al. | 75.4 ± 8.6 | 65 (48.8%) | 1.77 ± 0.18 | NA | NA | 111 (83.4%) | 27 (20.3%) | NA | 11 (8.2%) |
| Wilde et al. | 80 ± 6 | 141 (64.4%) | 1.88 ± 0.20 | 26.5 ± 5.0 | NA | NA | 70 (32%) | NA | 141 (64.4%) |
| Vamvakidou et al. | 75 ± 10 | 203 (70.7%) | 1.86 ± 0.20 | NA | NA | 202 (70.3%) | 126 (43.9%) | 112 (39.0%) | 103 (35.9%) |
| Hirsawa et al. | 72.8 ± 12.6 | 54 (54%) | 1.59 ± 0.19 | 23.3 ± 3.4 | NA | 63 (64%) | 25 (25%) | NA | NA |
| Gu et al. | 68.66 ± 13.6 | 117 (53.66%) | NA | 28 ± 4.9 | 73 (33.48%) | 172 (78.89%) | 42 (19.26%) | NA | 54 (23.86%) |
| Vamvakidou et al. | 75.0 ± 12.3 | 128 (58.7%) | 1.81 ± 0.22 | NA | NA | 116 (54.7%) | 51 (24.1%) | 89 (42%) | 54 (25%) |
| Saeed et al. | 67.4 ± 9.6 | 1622 (97.6%) | 1.90 ± 0.20 | 26.9 ± 4.4 | NA | 83 (5%) | NA | NA | NA |
| Bartko et al. | 73 ± 10 | 39 (83%) | 1.9 ± 0.2 | NA | NA | 37 (79%) | 17 (36%) | NA | NA |
| Clavel et al. | 71 ± 10 | 78 (77%) | 1.87 ± 0.23 | NA | NA | 60 (59%) | 40 (40%) | NA | 24 (24%) |
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