The clinical impact of transcatheter aortic valve replacement (TAVR) in patients with moderate mixed aortic valve disease (MMAVD)—characterized by the coexistence of moderate aortic stenosis (AS) and aortic regurgitation (AR)—remains unclear, as current evidence primarily focuses on isolated severe AS. This study aimed to compare outcomes of TAVR between patients with MMAVD and those with isolated severe AS. Between January 2019 and June 2024, 848 patients who underwent TAVR at our center were identified for analysis, including 75 with MMAVD and 773 with isolated severe AS. To minimize confounding, 73 MMAVD patients were matched with 264 isolated AS patients using 1:4 propensity score matching for comparative analysis. The primary endpoint was all-cause mortality; secondary endpoints included heart failure rehospitalization, left ventricular (LV) reverse remodeling, and procedural complications. Continuous variables were compared using independent samples t-tests, categorical variables using chi-square or Fisher’s exact tests, and survival using Kaplan–Meier curves with log-rank tests. At baseline, MMAVD patients exhibited greater LV dilation (LV end-diastolic diameter [LVEDD]: 56.07±9.04 vs 50.68±7.70, p < 0.001) and hypertrophy (LV mass index [LVMI]: 163.68±50.17 vs 151.59±44.38, p = 0.026). Post-TAVR, MMAVD showed superior reverse remodeling (ΔLVEDD: −7.18±9.75 vs −2.52±7.64, p < 0.001), though LVEF recovery was comparable (ΔLVEF: 5.47±13.98 vs 6.88±15.20, p = 0.52). Survival rates were similar (log-rank p = 0.370), but MMAVD had higher 1-year heart failure rehospitalization (5.97% vs 0.96%, p = 0.032). In conclusion, TAVR with self-expandable valves yields comparable survival in MMAVD and isolated AS, with more pronounced reverse remodeling in MMAVD despite advanced baseline disease.
Transcatheter aortic valve replacement (TAVR) has transformed the treatment landscape for elderly patients with severe degenerative aortic stenosis (AS). , With the advancement of transcatheter technology and accumulating clinical evidence, its indications have expanded beyond high-risk populations to include intermediate- and low-risk patients, as well as selected individuals with other forms of aortic valve pathology, such as pure aortic regurgitation (AR) and mixed aortic valve disease (MAVD). ,,,,
Moderate MAVD (MMAVD), defined as the concurrent presence of moderate AS and moderate AR, imposes both pressure and volume overload on the left ventricle, leading to complex hemodynamic consequences and a higher risk of adverse clinical outcomes. While current guidelines recommend that treatment decisions for MAVD be based on the predominant lesion, , emerging data suggest that MMAVD may be prognostically equivalent to severe isolated lesions. , In particular, patients with MMAVD exhibit clinical outcomes comparable to those with pure severe AS, and worse than those with isolated moderate AS or AR, prompting the need for re-evaluation of current management strategies.
Despite the growing recognition of this disease phenotype, data regarding the safety and efficacy of TAVR in patients with MMAVD remain limited. Whether early intervention in this subgroup may improve clinical outcomes is yet to be determined. In this study, we aimed to characterize the clinical and anatomical features of patients with MMAVD undergoing TAVR and to compare their outcomes with those of isolated AS patients.
Materials and Methods
Study design and patient selection
This single-center retrospective observational study included patients who underwent TAVR at West China Hospital, Sichuan University, between January 2019 and June 2024. Among these, patients diagnosed with either MMAVD (defined as concurrent moderate AS and moderate AR) or isolated severe AS (severe AS with none or mild AR) were included for analysis. Patients were excluded if they underwent emergency procedure, received TAVR for degeneration aortic bioprostheses, or had a quadricuspid aortic valve. Baseline clinical data, imaging measurements (echocardiography and computed tomography), procedural details, and follow-up outcomes were prospectively collected in a dedicated TAVR database. Self-expandable valves of supra-annular design were predominantly used during the procedure, and the procedural steps were consistent with those described previously. Mortality data were obtained from hospital records and structured telephone follow-up. The study was approved by the institutional ethics committee, and all patients provided written informed consent.
Echocardiographic assessment
All patients underwent transthoracic echocardiography (TTE) before TAVR and prior to hospital discharge, with scheduled follow-up examinations at 1,3 and 6 months postprocedure, and annually thereafter. The severity of AS and AR was graded as mild, moderate, or severe according to current international guideline recommendations. , All echocardiograms were interpreted by board-certified cardiologists blinded to clinical outcomes. Key echocardiographic parameters included peak transvalvular velocity (Vmax), mean pressure gradient (PG mean), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), and left ventricular mass index (LVMI).
Clinical outcomes
The primary outcome was all-cause mortality. Secondary outcomes were defined according to the Valve Academic Research Consortium-3 (VARC-3) criteria and included stroke, rehospitalization due to heart failure, new permanent pacemaker implantation, major bleeding, and vascular complications.
Statistical analysis
Continuous variables were expressed as mean ± SD and compared using the independent samples t-test. Categorical variables were presented as counts and percentages and compared using the chi-square test or Fisher’s exact test, as appropriate. Kaplan–Meier survival curves were constructed, and between-group differences were assessed using the log-rank test. To account for baseline differences and minimize potential confounding, propensity score matching (PSM) was performed using a 1:4 nearest-neighbor method with a caliper width of 0.2. The variables included in the propensity model were age, sex, aortic valve morphology (bicuspid vs tricuspid), NYHA functional class, hypertension, diabetes mellitus, chronic obstructive pulmonary disease (COPD), coronary artery disease, prior myocardial infarction, previous percutaneous coronary intervention (PCI), cerebrovascular disease, chronic kidney disease, and atrial fibrillation. All statistical analyses were performed using IBM SPSS Statistics software version 27.0 (IBM, Armonk, NY). All p-values were 2-sided, and a p-value < 0.05 was considered statistically significant.
Results
Study population
Between January 2019 and June 2024, a total of 1,710 patients underwent TAVR at West China Hospital, Sichuan University. Of these, 75 patients with MMAVD and 773 with isolated severe AS were identified for analysis. After 1:4 propensity score matching, 73 MMAVD patients were matched with 264 AS patients ( Figure 1 ). The median follow-up duration was 24 months.
Study flowchart. Study flowchart showing the selection process of the study population. AS = aortic stenosis; AR = aortic regurgitation; MAVD = mixed aortic valve disease; TAVR = transcatheter aortic valve replacement.
Table 1 summarizes the baseline characteristics of the unmatched and matched cohorts. Prior to matching, MMAVD patients tended to be younger (71.70 ± 8.11years vs 73.10 ± 7.51years, p = 0.101), had a lower proportion of females (34.67% vs 45.92%, p = 0.061), and higher prevalence of chronic lung disease (10.67% vs 6.99%, p = 0.242) and cerebrovascular disease (16.00% vs 10.48%, p = 0.144); however, none of these differences were statistically significant. Postmatching, all baseline variables were well balanced, with absolute standardized differences (ASD) <10% for most covariates.
Table 1
Baseline characteristics
| Unadjusted cohort | Propensity score-matched cohort | |||||||
|---|---|---|---|---|---|---|---|---|
|
MMAVD
( n = 75) |
Isolated AS
( n = 773) |
p value | ASD, % |
MMAVD
( n = 73) |
Isolated AS
( n = 264) |
p value | ASD, % | |
| Age, years | 71.70 ± 8.11 | 73.10 ± 7.51 | 0.101 | 17.91 | 71.90 ± 8.11 | 72.69 ± 7.99 | 0.461 | 9.81 |
| Female | 26 (34.67) | 355 (45.92) | 0.061 | 22.62 | 26 (36.11) | 97 (36.74) | 0.921 | 1.31 |
| BMI, kg/cm² | 23.03 ± 3.31 | 23.24 ± 3.47 | 0.619 | 6.19 | 22.98 ± 3.33 | 23.44 ± 3.54 | 0.337 | 13.39 |
| STS-PROM, % | 3.76 ± 3.85 | 3.38 ± 2.50 | 0.411 | 11.71 | 3.71 ± 3.80 | 3.48 ± 2.79 | 0.571 | 6.90 |
| NYHA class III/IV | 36 (48.00) | 352 (45.54) | 0.683 | 4.94 | 36 (50.00) | 136 (51.52) | 0.820 | 3.04 |
| Hypertension | 37 (49.33) | 332 (42.95) | 0.287 | 12.87 | 37 (51.39) | 135 (51.14) | 0.970 | 0.50 |
| Diabetes | 16 (21.33) | 162 (20.96) | 0.939 | 0.91 | 16 (22.22) | 62 (23.48) | 0.822 | 2.98 |
| Chronic lung disease | 8 (10.67) | 54 (6.99) | 0.242 | 14.14 | 7 (9.72) | 23 (8.71) | 0.790 | 3.54 |
| Coronary artery disease | 15 (20.00) | 182 (23.54) | 0.488 | 8.38 | 15 (20.83) | 55 (20.83) | 1.000 | 0.00 |
| Cerebral vascular disease | 12 (16.00) | 81 (10.48) | 0.144 | 17.67 | 10 (13.89) | 40 (15.15) | 0.836 | 3.54 |
| Chronic kidney disease | 7 (9.33) | 45 (5.82) | 0.211 | 14.63 | 5 (6.94) | 25 (9.47) | 0.790 | 8.87 |
| History of PCI | 13 (17.33) | 96 (12.42) | 0.225 | 14.67 | 11 (15.28) | 43 (16.29) | 0.505 | 2.75 |
| Atrial fibrillation | 9 (12.00) | 89 (11.51) | 0.900 | 1.53 | 9 (12.50) | 30 (11.36) | 0.790 | 3.56 |
Depicted are mean ± SD, or counts with percentages.
AS = aortic stenosis; ASD = absolute standardized difference; BMI = body mass index; MMAVD = moderate mixed aortic valve disease; NYHA = New York Heart Association; PCI = percutaneous coronary intervention; STS-PROM = Society of Thoracic Surgeons Predicted Risk of Mortality.
Imaging characteristics
As shown in Table 2 , patients with MMAVD exhibited significantly lower Vmax (3.67 ± 0.39m/s vs 4.84 ± 0.75m/s, p < 0.001) and PGmean (32.09 ± 7.55mmHg vs 58.99 ± 18.67mmHg, p < 0.001) than those with isolated AS, but had larger LVEDD (56.52 ± 9.30mm vs 49.72 ± 7.29mm, p < 0.001) and LVMI (163.68 ± 50.17g/m 2 vs 151.59 ± 44.38g/m², p = 0.026), and lower LVEF (55.09 ± 15.07% vs 59.08 ± 14.01%, p = 0.020). Computed tomography (CT) evaluation revealed a higher prevalence of tricuspid aortic valve morphology (77.33% vs 40.36%, p < 0.001), lower aortic valve calcification volume (163.8 ± 209.2mm vs 496.5 ± 466.3mm , p < 0.001), and larger annular and root dimensions in the MMAVD group. These findings largely persisted following PSM, except for LVMI, LVEF, and valve morphology.
Table 2
Imaging characteristics
| Unadjusted cohort | Propensity score-matched cohort | |||||||
|---|---|---|---|---|---|---|---|---|
|
MMAVD
(n = 75) |
Isolated AS
(n = 773) |
P value | ASD, % |
MMAVD
(n = 73) |
Isolated AS
(n = 264) |
P value | ASD, % | |
| Echocardiography | ||||||||
| Vmax, m/s | 3.67 ± 0.39 | 4.84 ± 0.75 | <0.001 | 195.74 | 3.68 ± 0.39 | 4.72 ± 0.71 | <0.001 | 181.56 |
| PGmean, mmHg | 32.09 ± 7.55 | 58.99 ± 18.67 | <0.001 | 188.90 | 32.04 ± 7.49 | 56.21 ± 16.98 | <0.001 | 184.18 |
| LVEDD, mm | 56.52 ± 9.30 | 49.72 ± 7.29 | <0.001 | 81.38 | 56.07 ± 9.04 | 50.68 ± 7.70 | <0.001 | 64.19 |
| LVMI, g/m² | 163.68 ± 50.17 | 151.59 ± 44.38 | 0.026 | 25.53 | 162.26 ± 49.24 | 152.02 ± 47.21 | 0.108 | 21.23 |
| LVEF, % | 55.09 ± 15.07 | 59.08 ± 14.01 | 0.020 | 27.42 | 55.83 ± 14.86 | 57.76 ± 14.72 | 0.326 | 13.05 |
| Computed tomography | ||||||||
| TAV | 58 (77.33) | 312 (40.36) | <0.001 | 74.55 | 55 (76.39) | 191 (72.35) | 0.493 | 9.12 |
| Annulus p, mm | 81.95 ± 10.36 | 76.46 ± 8.74 | <0.001 | 57.28 | 81.36 ± 9.88 | 76.40 ± 8.60 | <0.001 | 53.55 |
| LVOT p, mm | 85.41 ± 13.18 | 80.50 ± 12.15 | 0.001 | 38.74 | 84.64 ± 12.38 | 80.56 ± 11.74 | 0.013 | 33.82 |
| SOV p, mm | 118.06 ± 13.81 | 108.41 ± 13.15 | <0.001 | 71.57 | 117.62 ± 13.64 | 108.37 ± 13.69 | <0.001 | 67.69 |
| STJ p, mm | 101.45 ± 14.83 | 94.69 ± 13.79 | <0.001 | 47.21 | 101.22 ± 14.98 | 92.49 ± 13.29 | <0.001 | 61.65 |
| AAO d, mm | 41.64 ± 5.41 | 41.95 ± 6.06 | 0.692 | 5.40 | 41.55 ± 5.52 | 40.58 ± 5.92 | 0.234 | 16.95 |
| LCA h, mm | 13.73 ± 2.89 | 13.90 ± 3.56 | 0.639 | 5.24 | 13.52 ± 2.71 | 13.50 ± 3.23 | 0.973 | 0.67 |
| RCA h, mm | 16.06 ± 4.12 | 15.24 ± 3.63 | 0.075 | 21.12 | 15.96 ± 4.02 | 15.07 ± 3.33 | 0.063 | 24.11 |
| Calcium, mm 3 | 163.8 ± 209.2 | 496.5 ± 466.3 | <0.001 | 92.05 | 146.6 ± 181.5 | 436.2 ± 456.8 | <0.001 | 83.32 |
AAO = ascending aorta; ASD = absolute standardized difference; AS = aortic stenosis; d = diameter; h = height; LCA = left coronary artery; LVEDD = left ventricular end- diastolic dimension; LVEF = left ventricular ejection fraction; LVMI = left ventricular mass index; LVOT = left ventricular outflow tract; MMAVD = moderate mixed aortic valve disease; p = perimeter; PG mean = mean transprosthetic gradient; RCA = right coronary artery; SOV = sinus of Valsalva; STJ = sinotubular junction; TAV = tricuspid aortic valve; Vmax = maximum aortic valve velocity.
Procedural characteristics and complications
In the unmatched cohort, MMAVD patients were more likely to receive self-expanding valves (98.67% vs 91.46%, p = 0.027), less likely to undergo balloon predilation (68.00% vs 93.40%, p < 0.001) and postdilation (29.33% vs 46.31%, p = 0.005). Transfemoral access was used in nearly all cases, and rates of surgical conversion, annular rupture, tamponade, coronary obstruction, and major bleeding were low and comparable between groups. Balloon predilation remained less common (68.06% vs 90.91%, p < 0.001) in the MMAVD group after matching. No significant differences were observed in self-expanding valves, postdilation and major complications. No annular rupture or surgical conversion occurred in either group ( Table 3 ).
Table 3
Procedural characteristics and complications
| Unadjusted cohort | Propensity score-matched cohort | |||||
|---|---|---|---|---|---|---|
|
MMAVD
(n = 75) |
Isolated AS
(n = 773) |
p value |
MMAVD
(n = 73) |
Isolated AS
(n = 264) |
p value | |
| Transfemoral | 75 (100.00) | 765 (98.97) | 1.000 | 72 (100.00) | 262 (99.24) | 1.000 |
| Self-expandable valve | 74 (98.67) | 707 (91.46) | 0.027 | 71 (98.61) | 244 (92.42) | 0.057 |
| Balloon predilation | 51 (68.00) | 722 (93.40) | <0.001 | 49 (68.06) | 240 (90.91) | < 0.001 |
| Balloon postdilation | 22 (29.33) | 351 (46.31) | 0.005 | 21 (29.17) | 98 (38.13) | 0.162 |
| Conversion to surgery | 0 (0.00) | 1 (0.13) | 1.000 | 0 (0.00) | 0 (0.00) | – |
| Annulus rupture | 0 (0.00) | 0 (0.00) | – | 0 (0.00) | 0 (0.00) | – |
| Cardiac tamponade | 0 (0.00) | 5 (0.66) | 1.000 | 0 (0.00) | 3 (1.17) | 1.000 |
| Coronary obstruction | 3 (4.00) | 16 (2.12) | 0.242 | 3 (4.17) | 7 (2.73) | 0.462 |
| Bleeding | 0 (0.00) | 15 (1.98) | 0.385 | 0 (0.00) | 2 (0.78) | 1.000 |
| Vascular complication | 2 (2.67) | 47 (6.24) | 0.304 | 2 (2.78) | 17 (6.69) | 0.266 |
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