Can low-gradient aortic stenosis be predicted using a mathematic model? Integration of data from echocardiography, cardiac catheterization and cardiac magnetic resonance

Background Low-gradient aortic stenosis (LGAS) may account for approximately 40% severe AS defined as aortic valve area (AVA ≤1.0 cm2) and mean pressure gradient (MPG≤40 mmHg), which carries different outcome in comparison with high-gradient AS. Prior studies demonstrated that both pressure gradient and AVA are flow-dependent. There are few studies of the relationships among flow, gradient and AVA using mathematical models with multimodality imaging. Purpose To determine if LGAS would be predicated mathematically based on stroke volume (SV). Method Gorlin equation (AVA=Cardiac output/[SEP x HR x 44.3 √MPG]) can be rewritten as (AVA=SV/[SEP x 44.3 x √MPG]) when cardiac output and heart rate are replaced with SV (SV-based Gorlin equation). Systolic ejection period (SEP) was noninvasively measured from velocity profiles in 50 patients (20 female, mean ages 78 ± 9 years) with high-gradient severe AS (MPG=44 ± 8 mmHg) in sinus rhythm by echocardiography. Relationships between MPG (Y-axis) and SV (X-axis) were assessed by two mathematical models with AVA=1.0 cm2 and AVA=0.85 cm2 respectively. SV calculated with MPG =40 mmHg and AVA=1.0 cm2 was defined as the reference SV for MPG-AVA matched severe AS (dot A, Figure). SV measured by cardiac MRI in 5003 asymptomatic adult participants in MESA was obtained from our prior study to determine a normal distribution of SV with normal ejection fraction in United States population. Results Mean SEP was 0.336 sec from echocardiography, which was used in SV-based Gorlin equation. The reference SV for the MPG-AVA matched severe AS was 95 ml (dot A, Figure). With a decrease in SV (60 ml, dot B), an estimated mean PG would be 16 mmHg, although AVA was 1.0 cm2 leading to LGAS. MESA study showed that approximately 25% of asymptomatic adult had SV <95 ml. Female and seniors (≥ 75-year-old) had lower SV than male and young subjects. When AVA=0.85 cm2 was used as the criteria for severe AS, SV of 80 ml (dot C) would lead to MPG=40 mmHg (AVA matched severe AS). Both curves tended to merge together at lower SV, consistent with prior observations that Gorlin equation may not work well at low flow state. Conclusion LGAS may occur if SV does not meet the minimal requirement for generating MPG=40mmHg. Subjects with lower SV in general population are predisposed to develop LGAS if AVA ≤1.0 cm2 is used as a sole criterion for diagnosis of severe AS. High prevalence of LGAS is at least partially related to the current AS diagnostic criteria (AVA ≤1.0 cm2), which may overlook the varieties of SV in general population as well as in different ages and sex groups since the same AVA criteria is used for everyone.