Highlights
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TAVR with BEV vs SEV in patients with excessive cusp calcification.
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There was no significant differences in the rate of technical and device success.
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TAVR with BEV had a higher risk of annular rupture as compared to SEV.
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Patients with SEV required permanent pacemaker implantation more frequently.
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There were no significant differences in mortality throughout 5 years of follow-up.
ABSTRACT
Background
Excessive aortic cusp calcification increases the risk of periprocedural complications after transcatheter aortic valve replacement (TAVR). Differences in device performance in patients with excessive calcification may affect long-term clinical outcomes.
Objectives
To compare periprocedural and long-term outcomes between self-expanding (SEV) and balloon-expandable (BEV) prostheses in patients with excess cusp calcification undergoing TAVR.
Methods
Consecutive patients with severe aortic stenosis and aortic valve complex calcium volume ≥235 mm³ (on contrast images with Hounsfield unit threshold of 850) who underwent TAVR with either CoreValve/Evolut SEV or SAPIEN BEV from August 2007 to June 2023 were included from a prospective-single center registry. A 1:1 propensity-matched analysis was performed to account for baseline differences between groups.
Results
Among 1,345 patients with excessive cusp calcification undergoing TAVR, 271 matched pairs were identified. Procedural success was achieved in >85% of patients with no difference between groups. Annular rupture occurred more frequently with BEV compared to SEV (2.2% vs 0%, P =.030). SEV had a lower transprosthetic gradient (8.0 mmHg vs 11.2 mmHg, P <.001) but higher rates of mild or greater paravalvular regurgitation (69.7% vs 58.1%, P =.008) and new permanent pacemaker implantation (22.6% vs 15.5%, P =.001). At 5 years, there was no statistically significant difference in mortality between groups (45.1% vs 50.2%, P =.173).
Conclusions
In patients with excessive leaflet calcification undergoing TAVR, BEV had a higher risk of annular rupture, but a lower risk of paravalvular regurgitation, and a lower risk of permanent pacemaker implantation compared to SEV. Mortality was comparable between SEV and BEV throughout 5 years of follow-up.
Clinical Trial Registration
https://www.clinicaltrials.gov . NCT01368250.
Transcatheter aortic valve replacement (TAVR) has consistently proven noninferior or superior to surgical aortic valve replacement in a series of randomized trials. , The landmark trials established two transcatheter heart valve (THV) devices, the balloon-expandable SAPIEN (Edwards Lifesciences) and the self-expanding CoreValve/Evolut (Medtronic) family of devices, as the most commonly used valve types for TAVR across a broad spectrum of patients with aortic stenosis (AS). As TAVR is expanding to younger and lower-risk patients with longer life expectancy, optimal device selection based on clinical and anatomical features is getting more important to achieve optimal procedural results, device performance, and lifetime management.
Excessive aortic valve cusp calcification increases the risk of adverse procedural events, including THV underexpansion, malpositioning or migration, stroke, conduction disturbances, paravalvular regurgitation (PVR), coronary obstruction, and annular rupture. Additionally, excessive leaflet calcification may be associated with unfavorable bioprosthetic hemodynamics and an increased risk of late adverse events. ,, However, there is a paucity of data comparing BEV and SEV in patients with excessive calcification of the aorto-valvular apparatus. The aim of the present study was to compare procedural and 5-year clinical outcomes of BEV and SEV in patients with excessive cusp calcification undergoing TAVR.
Methods
Study design and population
The Bern TAVI registry, a prospective registry of consecutive patients undergoing TAVR for symptomatic severe AS, is part of the nationwide SwissTAVI Registry (ClinicalTrials.gov: NCT01368250). The present study focused on a subgroup of patients with severe AS and excessive calcification of the aortic cusps, who underwent TAVR with balloon-expandable (SAPIEN THV, SAPIEN XT, SAPIEN 3, SAPIEN 3 Ultra [Edwards Lifesciences]) or self‐expanding devices (CoreValve, Evolut R/PRO/PRO Plus [Medtronic]) between August 2007 and June 2023. The study was approved by the Bern ethics committee, and all individuals provided written informed consent for participation.
Aortic root assessment
Aortic root dimensions were evaluated by experienced imaging specialists in a dedicated Corelab. All preprocedural multi-detector computed tomography (MDCT) examinations were performed as previously described, and acquired images were transferred to a dedicated workstation (3mensio Structural Heart, 3mensio Medical Imaging BVNetherlands). ,,, The systolic phase of the MDCT image with the least motion artifact was selected for the analysis, and the images were reconstructed to obtain a double-oblique transverse reconstruction at the level of the basal aortic annulus ring using the built-in module. Aortic valve leaflet and left ventricular outflow tract (LVOT) calcium volume was quantified in the contrast images by using a Hounsfield unit threshold of 850. Excessive cusp calcification was defined as total aortic valve leaflet calcium volume ≥235 mm 3, which has been suggested to better discriminate the risk of significant PVR after TAVR ( Figure 1 ). LVOT calcification was assessed within the region of interest extending from the basal annular plane to a perpendicular plane 5 mm below it, and was classified semiquantitatively as none, mild, moderate, or severe, as described previously. Transcatheter heart valve sizing was retrospectively assessed using preprocedural CT as previously described. Sizing was considered suboptimal if the implanted valve size was outside the manufacturer-recommended annular range.
Self-expanding versus balloon-expandable TAVR prosthesis in patients with excessive aortic valve cusp calcification. BEV, balloon-expandable valve; LCC, left coronary cusp; NCC, non-coronary cusp; RCC, right coronary cusp; SEV, self-expanding valve; TAVR, transcatheter aortic valve replacement; THV, transcatheter heart valve; VARC, Valve Academic Research Consortium.
Data collection and clinical endpoints
Baseline clinical, procedural, and follow-up data were collected using standardized case report forms and were prospectively logged in a web-based database. Baseline echocardiographic data was independently re-evaluated by dedicated imaging specialists and integrated into the database. Clinical and echocardiographic follow-up was performed at 30 days and at 1-, 5-, and 10 years post TAVR. All adverse events were systematically collected and adjudicated by a dedicated clinical event committee on the basis of the VARC criteria applicable at the time of the procedure. ,, Technical and device success or failure were retrospectively adjudicated according to the VARC-3 criteria based on detailed documentation of adjudicated endpoints that form the individual components of the composite endpoints. ,, Structural valve deterioration was defined according to the VARC criteria between 2007 and 2013 and has since been defined according to the VARC-2 criteria. , Unplanned repeat aortic valve intervention was defined as a composite of valve-in-valve procedure, balloon valvuloplasty, surgical revision, or paravalvular leak closure. To avoid under- or over-reporting of THV deterioration, we retrospectively evaluated VARC-3 hemodynamic valve deterioration in patients who underwent TAVR between August 2007 and June 2022 based on the prospectively collected echocardiographic data. , An independent Clinical Trials Unit is responsible for central data monitoring to verify the completeness and accuracy of data and independent statistical analysis. Outcomes of interest in the present study included VARC-3 technical and device success and clinical outcomes throughout 5 years of follow-up after TAVR.
Statistical analysis
Categorical variables are reported as frequencies and percentages and compared using the Chi-square test or two-tailed Fisher’s exact test. Continuous variables are presented as mean values ± standard deviation (SD), or median (interquartile range [IQR]) depending on the normality of the distribution and compared accordingly using two-sample t test or Mann Whitney U test, as applicable. Adjudicated events are expressed as counts and incidence rates and are computed using the Kaplan–Meier method (censored at death or last valid contact—in case of awaiting next follow-up, or consent withdrawal). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confident intervals (CIs). To adjust confounding due to valve selection bias we conducted one-to-one propensity score matching of patients who received SEV vs BEV modelled with a multivariate logistic regression based on baseline clinical and imaging characteristics (Supplemental Appendix). A 1:1 greedy nearest neighbor matching protocol with a caliper of 0.2 was used for matching. Absolute standardized differences (ASDs) were estimated for all the baseline variables in the unmatched and matched cohorts to assess the balance in baseline demographics. An ASD < 0.10 was considered as an indicator of good balance. Given the potential difference in outcome based on device generation, patients treated with earlier generation THVs (Edwards SAPIEN THV/XT and Medtronic CoreValve) were matched independently. In addition, landmark analyses were performed with the landmark set at 1 year after TAVR. All statistical tests were 2-sided, and a P -value < 0.05 was considered significant. Statistical analyses were performed using Stata 15.1 (StataCorp, College Station, TX, USA).
Results
Study population and baseline characteristics
Among 3,973 patients who underwent TAVR at Bern University Hospital between August 2007 and June 2023, 1,345 patients with mean aortic valve complex calcium volume of 540.6 ± 311.5 mm 3 met the inclusion criteria and were included in the study ( Figure 2 and Supplementary Figure 1). Of these, 448 patients were treated with SEV and 897 with BEV. Baseline clinical, echocardiographic, and MDCT characteristics of the unmatched and matched cohorts are shown in Table I . Before propensity score matching, SEV recipients were older (83.5 ± 5.8 vs 81.6 ± 6.4 years, P <.001), less likely to be male (40.6% vs 71%, P <.001), more symptomatic (New York Heart Association functional class III/IV: 64.5% vs 53.8%, P <.001), had a higher Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score (5.3 ± 3.4 vs 4.2 ± 3.2, P <.001) and a higher prevalence of comorbidities (renal failure [estimated glomerular filtration rate <60 mL/min/1.73 m 2]: 72.5% vs 58.6%, P <.001; peripheral vascular disease: 16.1% vs 11.5%, = 0.020) compared with those with BEV. Coronary artery disease (48% vs 59.6%, P <.001) and previous myocardial infarction (10.9% vs 14.8%, P =.052) were less frequently observed in patients who received SEV as compared to BEV. On echocardiographic assessment, SEV recipients had a smaller aortic valve area (AVA) (0.64 ± 0.23 cm 2 vs 0.74 ± 0.23 cm 2, P <.001), a higher mean aortic valve pressure gradient (51.3 ± 18.1 mmHg vs 45.4 ± 15.2 mmHg, P <.001), and a higher prevalence of moderate or severe mitral regurgitation (22.4% vs 15.3%, P =.003). Aortic root dimensions as assessed by MDCT were smaller in patients with SEV as compared to BEV (aortic annulus area: 434.6 ± 95.3 mm 2 vs 494.4 ± 91.4 mm 2, P <.001; sinus of Valsalva: 32.0 ± 4.1 mm vs 33.9 ± 3.5 mm, P <.001; left and right coronary ostium height 14.4 ± 3.3 mm vs 15.8 ± 3.6 mm, P <.001, and 17.4 ± 3.4 mm vs 19.1 ± 3.4 mm, P <.001, respectively). Patients with SEV had a greater LVOT calcium volume (29.3 ± 63.3 mm 3 vs 17.4 ± 42.2 mm 3, P <.001), a higher prevalence of semiquantitative moderate or severe LVOT calcification (39.1% vs 29.1%, P <.001), a lower degree of aortic angulation (47.2 ± 8.8 degrees vs 50.8 ± 9.8 degrees, P <.001), and less annular eccentricity as determined by the ratio of minimum to maximum annular diameter (0.76 ± 0.07 vs 0.77 ± 0.06, P =.003). Propensity score-matching resulted in 271 pairs. After matching, both groups were well balanced with ASD 0.10 for all baseline clinical, echocardiographic, and MDCT variables ( Table I ).
Study flow chart. BEV, balloon-expandable valve; CT, computed tomography; SEV, self-expanding valve; TAVR, transcatheter aortic valve replacement; THV, transcatheter heart valve.
Table I
Baseline characteristics in the prematching and matched cohorts
| Pre-matching cohort | Matched cohort | |||||||
|---|---|---|---|---|---|---|---|---|
|
All patients
N = 1,345 |
SEV
N = 448 |
BEV
N = 897 |
P value |
SEV
N = 271 |
BEV
N = 271 |
P value | ASD | |
| Age, y | 82.2 ± 6.3 | 83.5 ± 5.8 | 81.6 ± 6.4 | <.001 | 83.2 ± 5.8 | 83.3 ± 5.8 | .736 | 0.029 |
| Male, n (%) | 819 (60.9%) | 182 (40.6%) | 637 (71.0%) | <.001 | 117 (43.2%) | 123 (45.4%) | .666 | 0.045 |
| Body mass index, kg/cm² | 25.8 ± 5.0 | 25.1 ± 5.3 | 26.2 ± 4.8 | <.001 | 25.2 ± 5.0 | 25.2 ± 4.9 | .964 | −0.004 |
| STS-PROM, % | 4.5 ± 3.3 | 5.3 ± 3.6 | 4.2 ± 3.2 | <0.001 | 5.1 ± 3.2 | 5.1 ± 3.0 | .976 | 0.003 |
| NYHA functional class III or IV, (%) | 771 (57.4%) | 289 (64.5%) | 482 (53.8%) | <.001 | 165 (60.9%) | 171 (63.1%) | .658 | 0.046 |
| Urgent TAVR, n (%) | 28 (2.1%) | 13 (2.9%) | 15 (1.7%) | .157 | 4 (1.5%) | 4 (1.5%) | 1.00 | <0.001 |
| Concomitant disease | ||||||||
| Hypertension, n (%) | 1,130 (84.0%) | 368 (82.1%) | 762 (84.9%) | .206 | 226 (83.4%) | 223 (82.3%) | .82 | −0.029 |
| Diabetes mellitus, n (%) | 323 (24.0%) | 94 (21.0%) | 229 (25.5%) | .068 | 56 (20.7%) | 56 (20.7%) | 1.00 | <0.001 |
| Dyslipidemia, n (%) | 874 (65.0%) | 282 (62.9%) | 592 (66.0%) | .275 | 163 (60.1%) | 161 (59.4%) | .930 | −0.015 |
| CKD (eGFR <60 mL/min/1.73 m 2), n (%) | 850 (63.2%) | 325 (72.5%) | 525 (58.6%) | <.001 | 191 (70.5%) | 189 (70.0%) | .925 | −0.010 |
| COPD, n (%) | 150 (11.2%) | 59 (13.2%) | 91 (10.1%) | .099 | 30 (11.1%) | 36 (13.3%) | .512 | 0.068 |
| Atrial fibrillation, n (%) | 392 (29.1%) | 123 (27.5%) | 269 (30.0%) | .341 | 80 (29.5%) | 87 (32.1%) | .577 | 0.056 |
| Previous history | ||||||||
| Previous CVE, n (%) | 152 (11.3%) | 52 (11.6%) | 100 (11.1%) | .855 | 26 (9.6%) | 30 (11.1%) | .672 | 0.048 |
| Coronary artery disease, n (%) | 750 (55.8%) | 215 (48.0%) | 535 (59.6%) | <.001 | 139 (51.3%) | 135 (49.8%) | .797 | −0.029 |
| Previous PCI, n (%) | 331 (24.6%) | 100 (22.3%) | 231 (25.8%) | .179 | 60 (22.1%) | 57 (21.0%) | .835 | −0.027 |
| Previous MI, n (%) | 182 (13.5%) | 49 (10.9%) | 133 (14.8%) | .052 | 36 (13.3%) | 40 (14.8%) | .711 | 0.042 |
| Previous CABG, n (%) | 107 (8.0%) | 30 (6.7%) | 77 (8.6%) | .241 | 18 (6.6%) | 18 (6.6%) | 1.00 | 0.000 |
| Peripheral artery disease, n (%) | 175 (13.0%) | 72 (16.1%) | 103 (11.5%) | .020 | 36 (13.3%) | 35 (12.9%) | 1.00 | −0.011 |
| Previous pacemaker, n (%) | 86 (6.4%) | 28 (6.2%) | 58 (6.5%) | 1.000 | 17 (6.3%) | 14 (5.2%) | .712 | −0.048 |
| Echocardiographic characteristics | ||||||||
| LVEF, % | 55.6 ± 13.0 | 55.8 ± 12.8 | 55.5 ± 13.1 | .722 | 57.2 ± 11.9 | 56.8 ± 12.2 | .738 | −0.029 |
| LVEF ≤40% | 206 (16.2%) | 67 (15.7%) | 139 (16.5%) | .748 | 33 (12.2%) | 37 (13.7%) | .701 | 0.044 |
| Aortic valve area, cm² | 0.70 ± 0.23 | 0.64 ± 0.23 | 0.74 ± 0.23 | <.001 | 0.66 ± 0.22 | 0.66 ± 0.21 | .952 | 0.005 |
| Mean aortic valve pressure gradient, mmHg, n(%) | 47.4 ± 16.4 | 51.3 ± 18.1 | 45.4 ± 15.2 | <.001 | 49.1 ± 17.4 | 49.0 ± 16.8 | .958 | −0.005 |
| Moderate or severe aortic regurgitation, n (%) | 128 (9.5%) | 49 (11.0%) | 79 (8.8%) | .236 | 26 (9.6%) | 23 (8.5%) | .765 | −0.039 |
| Moderate or severe mitral regurgitation, n (%) | 202(17.7%) | 87 (22.4%) | 115 (15.3%) | .003 | 48 (19.9%) | 47 (19.9%) | 1.00 | <0.001 |
| Moderate or severe tricuspid regurgitation, n (%) | 104 (10.5%) | 39 (13.0%) | 65(9.4%) | .092 | 28 (13.0%) | 25 (11.7%) | .769 | −0.041 |
| CT imaging data | ||||||||
| Bicuspid aortic valve, n (%) | 100 (7.4%) | 28 (6.2%) | 72 (8.0%) | .271 | 14 (5.2%) | 16 (5.9%) | .851 | 0.032 |
| Annulus area, mm² | 474.47 ± 96.88 | 434.6 ± 95.3 | 494.4 ± 91.4 | <.001 | 438.2 ± 85.8 | 445.4 ± 77.6 | .305 | 0.088 |
| Sinus of Valsalva, mm | 33.3 ± 3.8 | 32.0 ± 4.1 | 33.9 ± 3.5 | <.001 | 31.8 ± 3.2 | 31.9 ± 3.3 | .645 | 0.040 |
| Left coronary height, mm | 15.3 ± 3.6 | 14.4 ± 3.3 | 15.8 ± 3.6 | <.001 | 14.7 ± 3.3 | 14.8 ± 3.4 | .701 | 0.033 |
| Right coronary height, mm | 18.5 ± 3.5 | 17.4 ± 3.4 | 19.1 ± 3.4 | <.001 | 17.5 ± 3.2 | 17.7 ± 3.1 | .471 | 0.062 |
| AVC calcium, mm³ | 540.6 ± 311.5 | 542.6 ± 313.6 | 539.6 ± 310.5 | .868 | 530.8 ± 276.2 | 531.0 ± 301.2 | .996 | <0.001 |
| LVOT calcium, mm³ | 21.4 ± 50.5 | 29.3 ± 63.3 | 17.4 ± 42.2 | <.001 | 25.0 ± 59.3 | 26.7 ± 61.0 | .752 | 0.027 |
| Moderate or severe LVOT calcification, n (%) | 436 (32.4%) | 175 (39.1%) | 261 (29.1%) | <.001 | 101 (37.4%) | 96 (35.4%) | .656 | −0.041 |
| Aortic angulation, | 49.6 ± 9.6 | 47.2 ± 8.8 | 50.8 ± 9.8 | <.001 | 48.0 ± 8.6 | 47.8 ± 10.1 | .762 | −0.026 |
| Eccentricity of annulus | 0.77 ± 0.07 | 0.76 ± 0.07 | 0.77 ± 0.06 | .003 | 0.76 ± 0.08 | 0.76 ± 0.06 | .777 | −0.024 |
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