Transvalvular Flow Rate Determines Prognostic Value of Aortic Valve Area in Aortic Stenosis

Abstract

Background: Aortic valve area (AVA) ≤1.0 cm² is a defining characteristic of severe aortic stenosis (AS). AVA can be underestimated at low transvalvular flow rate. Yet, the impact of flow rate on prognostic value of AVA ≤1.0 cm² is unknown and is not incorporated into AS assessment.

Objectives: This study aimed to evaluate the effect of flow rate on prognostic value of AVA in AS.

Methods: In total, 1,131 patients with moderate or severe AS and complete clinical follow-up were included as part of a longitudinal database. The effect of flow rate (ratio of stroke volume to ejection time) on prognostic value of AVA ≤1.0 cm² for time to death was evaluated, adjusting for confounders. Sensitivity analysis was performed to identify the optimal cutoff for prognostic threshold of AVA. The findings were validated in a separate external longitudinal cohort of 939 patients.

Results: Flow rate had a significant effect on prognostic value of AVA. AVA ≤1.0 cm² was not prognostic for mortality (p = 0.15) if AVA was measured at flow rates below median (≤242 ml/s). In contrast, AVA ≤1.0 cm² was highly prognostic for mortality (p = 0.003) if AVA was measured at flow rates above median (>242 ml/s). Findings were irrespective of multivariable adjustment for age, sex, and surgical/transcatheter aortic valve replacement (as time-dependent covariates); comorbidities; medications; and echocardiographic features. AVA ≤1.0 cm² was also not an independent predictor of mortality below median flow rate in the validation cohort. The optimal flow rate cutoff for prognostic threshold was 210 ml/s.

Conclusions: Transvalvular flow rate determines prognostic value of AVA in AS. AVA measured at low flow rate is not a good prognostic marker and therefore not a good diagnostic marker for truly severe AS. Flow rate assessment should be incorporated into clinical diagnosis, classification, and prognosis of AS.

Keywords: aortic stenosis; flow rate; low flow; low gradient; outcome; prognosis.

Figure 1:. Relationship between aortic stenosis subgroups and flow rate (Q). Panel A: Subgroups of AS by flow rate; Panel B: Flow rates in high gradient vs. low gradient severe AS.

101/197 (51%) of high gradient severe AS had Q ≤ median. 312/383 (82%) of low gradient AS had Q ≤ median (≤242mL/s). Abbreviations: Sev AS HG: high gradient severe AS (n=197); Mod AS LG: moderate AS with low gradient (n=536); Sev AS LG: low gradient severe AS (n=383); Mod AS HG: moderate AS with high gradient (n=15); Q: transvalvular flow rate.

Figure 2:. Flow rate by sex.

297/454 (65%) female patients had Q ≤ median (≤242mL/s). 269/677 (40%) of male patients had Q ≤ median. Abbreviation: Q: transvalvular flow rate.

Figure 3:. Survival in aortic stenosis stratified by resting transvalvular flow rate below and above the median.

Patients with flow rate below the median (≤242mL/s) had worse overall survival than patients with flow rate above the median. Abbreviation: Q: transvalvular flow rate.

Figure 4:. Stroke volume versus flow rate classification of flow state.

While 265/320 (82.8%) of patients with low stroke volume index had flow rate below median (≤212 mL/s), 205/619 (33.1%) of patients with normal stroke volume index also had flow rate below median in the validation cohort. Abbreviation: Q: transvalvular flow rate.

Figure 5:. Survival stratified by flow rate in patients with normal stroke volume index (≥35mL/m²).

In the validation cohort, even in patients with normal stroke volume index, flow rate below the median (≤212mL/s) was associated with worse overall than flow rate above the median. Abbreviation: Q: transvalvular flow rate.

Central Illustration:. Algorithm for incorporation of flow rate into assessment of Aortic Stenosis.

AVA measured at Q >210mL/s is prognostic for mortality and therefore valid as a marker of severe AS. Abbreviations: AS: aortic stenosis; AVA: aortic valve area, MG: mean gradient, Q: flow rate. *Further assessment when AVA is invalid may include augmentation of Q and/or use of alternative modalities including computed tomography calcium score.