The Effect of Volume-Flow Discordance on Survival in Severe Aortic Stenosis

Figures

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  Figure 1. Study Cohort Selection Flow Diagram 423 patients >65 years of age with severe aortic stenosis (AS) underwent transcatheter aortic valve replacement (TAVR) over a 5-year period.4 Fifty-three patients were excluded due to aortic valve area (AVA) >1 cm2, and 47 due to incomplete clinical or echocardiographic data. A further 32 patients were excluded due to missing stroke volume index (SVi) data at time of transthoracic echocardiogram (TTE), leaving 291 patients with complete data available for 3-year survival analysis.

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  Figure 2. Distribution of V-Q Discordance Groups by AS Category Distribution of V-Q discordance phenotypes (groups 1-4) across AS categories. Bars represent the percentage distribution of each V-Q discordance group within AS categories, normalized to 100%. Group 1 (low V-Q concordance; blue) and group 3 (normal V-Q concordance; light blue) represent concordant phenotypes. Group 2 (low V-Q discordance; dark grey) and group 4 (normal V-Q discordance; light grey) represent discordant phenotypes. Although visual differences are evident across AS subtypes, the chi square test did not reach statistical significance (P = 0.109). LFLG = low-flow, low-gradient; Q = flow; V = volume; other abbreviation as in Figure 1.

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  Figure 3. Kaplan-Meier Survival Curves Survival analysis of 291 study participants stratified by V-Q discordance group. Accompanying table shows the number of individuals at risk each year of follow-up stratified by group. A total of 43 deaths (15%) occurred during follow-up (median time to death: 1.0 years). Overall survival did not differ significantly across the four groups (log-rank P = 0.109). Three-year survival was comparable between the low V-Q discordance group (group 2) and the normal V-Q concordance group (group 3; log-rank P = 0.69). In contrast, 26 deaths occurred in participants with low V-Q concordance (group 1), compared with 6 in the low V-Q discordance group (group 2), corresponding to 3-year cumulative survival rates of 73.8% vs 86.0% (log-rank P = 0.030). Among participants with normal V-Q patterns, 17 deaths occurred in the concordant group (group 3) compared to 3 in the discordant group (group 4), with 3-year cumulative survival rates of 83.2% vs 92.9% (log-rank P = 0.135). Abbreviations as in Figure 2.

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  Figure 4. Adjusted HRs for All-Cause Mortality Comparing Groups 1 and 2 Forest plot showing results of a multivariable Cox proportional hazards regression model assessing the association between discordance phenotype and survival. Discordance group 2 was associated with a lower, though nonsignificant, hazard of mortality compared to group 1, with an adjusted HR of 0.50 (95% CI: 0.13-1.94). The model was adjusted for AS subtype, including AS category 2 (discordant severe AS), category 3 (LF-LG AS), and category 4 (paradoxical LF-LG AS), with category 1 (classical severe AS) as the reference. AS category 3 was significantly associated with increased mortality (HR: 3.42, 95% CI: 1.10-10.64). The vertical dashed line indicates the null effect (HR: 1.00). Error bars represent 95% CIs. Abbreviations as in Figure 2.

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  Figure 5. Number of Individuals at Risk Each Year of Follow-Up Stratified by Group Number of individuals at risk at each year of follow-up, stratified by volume–flow (V-Q) concordance and discordance groups. Group 1: Low V-Q concordance; Group 2: High V-Q discordance; Group 3: High V-Q concordance; Group 4: Low V-Q discordance. Values represent the number of participants remaining in each group at the start of each follow-up year (0-3 years).

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  Figure 6. Decision Curve Analysis Decision curve analysis showing the standardized net benefit of using low V-Q concordance (group 1), SVi <35 mL/m2, and total flow reserve (TFR) <210 mL/min for predicting 3-year mortality after TAVR. Across a range of clinically relevant threshold probabilities (5%-25%), the low V-Q model (red) showed superior net benefit compared to conventional hemodynamic thresholds. The "all" and "none" curves represent strategies of treating all or no patients, respectively. These results support the added clinical utility of V-Q discordance in risk stratification beyond established flow-based metrics. TFR = transvalvular flow reserve; other abbreviations as in Figures 1 and 2.

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  Central Illustration. The Impact of Volume-Flow Discordance on Survival in Aortic Stenosis Patients were classified into 4 hemodynamic groups based on stroke volume index (SVi) and transvalvular flow rate (TFR). Group 1 (36%), classified as low V-Q concordance, had an SVi ≤35 mL/m2 and a TFR <210 mL/s. Group 2 (15%), defined as low V-Q discordance, had an SVi ≤35 mL/m2 but paradoxically a TFR ≥210 mL/s. Group 3 (35%), categorized as normal V-Q concordance, had an SVi >35 mL/m2 and a TFR ≥210 mL/s. Group 4 (14%), defined as normal V-Q discordance, had an SVi >35 mL/m2 but a TFR <210 mL/s. Among patients with an SVi ≤35 mL/m2, those with low V-Q discordance had significantly better 3-year survival (P = 0.030, log-rank), comparable to patients with an SVi >35 mL/m2. AS = aortic stenosis; Q = flow; SVi = indexed stroke volume; TAVR = transcatheter aortic valve replacement; TFR = transaortic flow rate; V = volume.