https://orcid.org/0000-0002-8373-8486
Abstract
We sought to assess whether post-implant transcatheter aortic valve prosthesis multidetector computed characteristics differ between patients with native tricuspid and bicuspid aortic valve stenosis, as well as the effect on valve performance and clinical implications.
We analysed 100 consecutive post-implant multidetector computed tomography scans to assess self-expandable prosthesis non-uniform expansion at 6 pre-specified valvular levels, and other specific parameters, including valvular and perivalvular thrombosis at 6 months follow-up. Echocardiographic prosthesis performance and clinical outcome were also evaluated.
Mean eccentricity was significantly higher in the bicuspid group (0.43 (0.09) vs 0.37 (0.08), P = 0.005, bicuspid vs tricuspid); valvular and perivalvular thrombosis were also significantly more frequent in the bicuspid than in the tricuspid group (81% vs 36.9%, P = 0.031); there was no significant difference in terms of mean prosthetic gradient at follow-up between (7.31 (5.53 mmHg) vs 7.09 (3.05 mmHg), P = 0.825); EOAi (indexed effective orifice area) was also similar between bicuspid and tricuspid (1.08 (0.12 cm2) vs 1.03 (0.13 cm2), P = 0.101), with no significant changes compared to discharge. However, the bicuspid valve was associated with a significantly higher risk of adverse events (HR: 3.72, 95% CI: 1.07–13.4, P = 0.027).
Higher level of eccentricity, which indicates prosthesis deformation, is often detected in bicuspid valves. Although echocardiographic performance was not affected, this might have led to an increased incidence of thrombosis at valvular and perivalvular levels and worse outcomes.
INTRODUCTION
Prosthesis durability and identification of early signs and predictors of dysfunction are pivotal because transcatheter aortic valve implantation (TAVI) is now a therapeutic option for younger patients at low risk for surgery and with prolonged life expectancy [1].
Indications for TAVI are also expanding in stenotic bicuspid valves; however, there are conflicting results regarding prosthesis performance in this setting. As an example, a recent trial has reported a worrisome incidence of adverse events at 1-year follow-up in patients with bicuspid aortic stenosis treated with TAVI [2], while a previous multicentre study has shown favourable results in a similar population [3].
Stenotic bicuspid valves are challenging because of the ellipticity of the native annulus, which may result in non-uniform prosthesis expansion, also known as prosthesis deformation [4].
Few studies have investigated post-implant prosthesis deformation in tricuspid and bicuspid aortic stenosis and its consequences in the context of self-expandable valves [5, 6]. Hence, whether derangement from the normal post-implant anatomy leads to prosthetic valve dysfunction remains unknown. Notably, valvular and perivalvular thromboses are common phenomena following TAVI and may be regarded as early subclinical signs of structural valve deterioration [7–9], yet whether the prevalence of post-implant thrombosis differs between tricuspid and bicuspid requires further investigation [10].
Thus, the aims of this study were as follows:
To analyse with multidetector computed tomography (MDCT) post-implant Evolut R (Medtronic Inc., Minneapolis, USA) morphology and prosthesis-host factors, which include: (i) eccentricity index calculated at 6 prespecified prosthesis levels (Fig. 1), (ii) commissural alignment, (iii) leaflet expansion, (iv) implantation depth and (v) valve-to-coronary sinus distance.
To describe the incidence and different localizations of valvular and perivalvular thrombosis, in patients with tricuspid and bicuspid aortic valve stenosis [9, 11].
MDCT measurements of major and minor diameters were performed at 6 levels of the prosthetic valve (Medtronic Inc., Minneapolis, USA): (i) frame inflow (nadir of the prosthesis), (ii) native annulus, (iii) leaflet inflow (nadir of the prosthetic leaflets), (iv) prosthesis waist (the waist between the leaflet outflow and the leaflet inflow levels), (v) leaflet outflow (the 3 commissural tabs of the prosthetic leaflets), (vi) frame outflow (tip of the prosthesis). MDCT: multi detector computed tomography.
Additionally, prosthesis haemodynamic performance and clinical outcomes were also evaluated [12].
PATIENTS AND METHODS
Study type, patient population and ethics
The present study was the MDCT substudy of the ‘EndoTAVI Project’, a European grant funded study (P.O.C. FESR SICILIA 2014/2020, Azione 1.1.1/https://www.euroinfosicilia.it/poc-20142020-azione, other details at www.endotavi.it) to evaluate predictors of early dysfunction after surgical and TAVI (www.endotavi.it), conducted at Maria Eleonora Hospital GVM Care&Research, a tertiary university centre in Palermo, Italy.
This prospective study included one-hundred consecutive patients with severe tricuspid and bicuspid aortic valve stenosis who underwent transfemoral TAVI with Evolut R between January 2019 and September 2023 and 2D transthoracic echocardiography and MDCT evaluation at 6-month follow-up (Supplementary Material, Fig. S1: Study Flow). Patients were enrolled before the procedure. The full inclusion and exclusion criteria have been reported elsewhere [9] and are provided in the Supplementary Material.
In brief, the key exclusion criteria were moderate–severe renal insufficiency prohibiting MDCT imaging (estimated glomerular filtration rate <40 ml/min/1.73 m2 of body surface area) or atrial fibrillation that could not be controlled to a ventricular response rate <60 beats/min. New/direct oral anticoagulants, vitamin K antagonist or dual antiplatelet therapy did not represent an exclusion criterion ‘per se’. Patients were discharged on lifelong aspirin unless oral anticoagulants or dual antiplatelet therapy were otherwise indicated (i.e. atrial fibrillation/recent coronary stent).
The study was performed in accordance with the Second Declaration of Helsinki, followed by the Strengthening the Reporting of Observational Studies in Epidemiology recommendations [13] and was approved by the Scientific Ethics Committee of the University of Palermo (Comitato Etico (CE) University of Palermo, latest protocol approval 1/2020)). All patients provided written informed consent before enrolment in the study.
Outcomes of interest
The primary outcomes were as follows:
MDCT evaluation of post-implant non-uniform expansion—prosthesis deformation in patients with tricuspid and bicuspid valve stenosis.
Assessment of any hypoattenuated lesions that indicate subclinical thrombosis at leaflet level (subclinical leaflet thrombosis (SLT)/hypoattenuated leaflet thickening (HALT)) or perivalvular level (i.e. anatomic sinus or subvalvular thrombosis) [9, 11].
The secondary outcomes were as follows:
Evaluation of bioprosthetic valve dysfunction according to the Valve Academic Research Consortium-3 criteria (VARC-3) haemodynamic structural valve definition that included increase in mean transvalvular gradient ≥10 mmHg resulting in mean gradient ≥20 mmHg with concomitant decrease in effective orifice area ≥0.3 cm2 compared with echocardiographic assessment performed at hospital discharge [12]. Non-structural valve dysfunction, defined as moderate total aortic regurgitation or moderate/severe prosthesis–patient mismatch, was also assessed [12].
Evaluation of early clinical outcomes such as transient ischaemic attack, stroke and cardiovascular rehospitalization for procedural—valvular and non-valvular-related causes [12].
Echocardiographic data were obtained at baseline, hospital discharge and 6-month follow-up.
Multi detector computed tomography analysis
Pre- and post-procedural contrast—enhanced MDCT scans were performed using Siemens Healthcare GmbH SOMATOM Drive (VB 20, 2019). The analysis was performed using dedicated post-processing software (Syngo.via™ Siemens Healthcare GmbH, Forchheim, Germany).
Definition of non-uniform expansion—prosthesis deformation
Given the Evolut R hourglass shape with varying cross-sectional areas throughout the frame, the minimum (Dmin) and maximum (Dmax) prosthesis diameters were measured at 6 pre-specified levels, as shown in Fig. 1, which included: (i) frame inflow (nadir of the prosthesis), (ii) native annulus, (iii) leaflet inflow (nadir of the prosthetic leaflets), (iv) prosthesis waist between the leaflet outflow and the leaflet inflow levels, (v) leaflet outflow (3 commissural tabs of prosthetic leaflets) and (vi) frame outflow (tips of prosthesis), as previously described.
The eccentricity index ranges from 0 to 1. A larger eccentricity index (close to 1) represents a configuration similar to that of an oval shape, whereas a smaller index (close to 0) represents a circular orientation [9, 14].
Other MDCT parameters included: commissural alignment, leaflet expansion, implantation depth, and valve-to-coronary distance and the calculation method is described in Supplementary Material.
Morphology and classification of bicuspid valve
We used the Sievers and Schmidtke bicuspid morphological classification based on the number of raphes (types 0, I and II) since it has been the most widely adopted [15].
Hypoattenuated leaflet lesions
It was defined as HALT/SLT (<200 Hounsfield units (HU)) of meniscal shape (> 2 mm) on the prosthetic leaflet surface (1 or more leaflets) visualized during the diastolic phase of leaflet coaptation on at least 2 planes [7] (Fig. 2A). The extent of HALT was graded on the long axis regarding involvement along the curvilinear leaflet beginning at the base using a five-tier grading scale: no HALT, HALT25%, HALT >25–50%, HALT >50–75% and HALT > 75% [16]. Per-patient severity was defined as the leaflet with the highest grade of HALT [16]. Restricted leaflet movement (RELM) was defined as a hypoattenuated lesion visualized during systolic phase-maximal leaflet opening, which determines restricted mobility in 1 or more leaflets. RELM was further categorized as no RELM, RELM 25%, RELM >25–50%, RELM > 50–75% and RELM > 75% [16]. HALT with RELM >50% signified an empirically set threshold for significantly reduced leaflet motion [7].
Schematic and MDCT representation of different locations of hypoattenuated lesions that suggest the presence of thrombus at (A) valvular level; (B) subvalvular level (prosthesis inner skirt); (C) anatomic sinus level. MDCT: multidetector computed tomography.
Hypoattenuated anatomic sinus lesion
It was defined as hypoattenuated thickening (<200 HU), at least > 2 mm in diameter, within the anatomic sinus (Fig. 2B), without enhancement of the contrast media between the sinus of Valsalva and implanted prosthesis [16].
Hypoattenuated subvalvular lesion
It was defined as circumferential hypoattenuating low-density thickening (<200 HU) of the prosthetic pericardial inner skirt ≥2 mm in diameter, visualized on at least 2 planes, extending from the nadir of the prosthetic leaflets towards the prosthesis inflow (Fig. 2C) [9, 17].
Lesion adjudication and grading
MDCT hypoattenuated lesion adjudication and grading were performed by 1 experienced radiologist (S.M.) and 1 biomedical engineer (A.Z.-H.). The device-host characteristics (i.e. prosthesis eccentricity, implantation depth, etc.) were analysed by M.M. and G.Z. Any disagreements were resolved by the last author.
The first, second and last authors and F.T. (study coordinator) had full access to the data. The authors vouch for the accuracy and completeness of the data and fidelity of the protocol.
Statistical analysis
Data were prospectively collected in an ad hoc digital case report form. Data were checked for normality using the Shapiro–Wilks test. Continuous, normally distributed variables are presented as the mean and standard deviation (SD), or as the median and interquartile range (IQR). Categorical variables are presented as number and percentages. Intergroup comparisons were performed with the two-tailed Student’s t-test (continuous variables) or the χ2 test (categorical variables) for unpaired data. The non-parametric Mann–Whitney U-test was used for continuous variables with a nonnormal distribution and Fisher’s exact test was used for categorical variables in the case of small expected cell sizes. Mixed model was also used to compare repeated measures (EOAi (indexed effective orifice area)). A time-to-event analysis using Kaplan–Meier estimates was used for analyses of neurological events or re-hospitalization (valvular and non-valvular related); the log-rank test and hazard ratio (HR) were used for outcome comparisons between exposure (bicuspid vs tricuspid).
Analyses and data modelling were performed using R-project (version 2023.12. R project for Statistical Computing) and R-studio (www.rstudio.com).
RESULTS
Patient population, baseline and procedural characteristics
The study flow/consort diagram is shown in Supplementary Material, Fig. S1. Among the 339 patients screened for study inclusion, a total of 100 had available MDCT scans at 6-month follow-up (mean 182, standard deviation: (SD) 12 days) with sufficient image quality to allow the assessment of eccentricity and valvular and perivalvular thrombosis and leaflet excursion (i.e. evaluation of RELM).
The overall patient population and baseline characteristics stratified by tricuspid vs bicuspid native valve are shown in Table 1. Native bicuspid aortic valve stenosis was detected in 16 patients; as shown in Fig. 3, 2 patients had no rafes, 13 had 1 rafe and 1 had 2 rafes. There was no significant difference between the tricuspid and bicuspid groups in terms of baseline characteristics, except that body mass index was significantly higher in the tricuspid group. More post-implant TAVI valvuloplasty procedures were performed in the bicuspid group.
Native bicuspid valve breakdown according to Sievers classification. AP: antero-posterior. NC: non coronary. L: left. R: right.
Characteristics of the patients at baseline and procedural details: tricuspid versus bicuspid group
| Overall cohort (N = 100) | Native valve type | |||
|---|---|---|---|---|
| Tricuspid (N = 84) | Bicuspid (N = 16) | P-value | ||
| Age (year) | 78.2 (5.8) | 77.9 (5.9) | 79.6 (5.3) | 0.311 |
| BSAa (m2) | 1.7 (0.2) | 1.7 (0.2) | 1.6 (0.1) | 0.001 |
| BMIb | 27.8 (5.0) | 28.5 (5.0) | 24.6 (3.4) | 0.004 |
| Male sex, n (%) | 53 (53.0) | 45 (53.6) | 8.0 (50.0) | 0.992 |
| Euroscore II, % | 1.79 (1.5, 2.3) | 1.7 (1.5, 2.2) | 1.85 (1.4, 2.3) | 0.102 |
| Low flow—low gradient, n (%) | 11(11.0) | 10 (11.9) | 1 (6.2) | 0.825 |
| NYHA functional classes III–IV, n (%) | 13 (13.0) | 9.0 (10.7) | 4.0 (25.0) | 0.245 |
| NIDDM/IDDM, n (%) | 30 (30.0) | 27 (32.1) | 3 (18.8) | 0.439 |
| Hypertension, n (%) | 98 (98.0) | 82 (97.6) | 16 (100.0) | 0.991 |
| COPD, n (%) | 18 (18.0) | 14 (16.7) | 4 (25.0) | 0.660 |
| Previous stroke/TIA, n (%) | 4 (4.0) | 2 (2.4) | 2 (12.5) | 0.234 |
| Previous PCI, n (%) | 22 (22.0) | 19 (22.6) | 3 (18.8) | 0.983 |
| Previous cardiac surgery, n (%) | 9 (9.0) | 9 (10.7) | 0 (0) | 0.372 |
| Previous MI, n (%) | 17 (17.0) | 15 (17.9) | 2 (12.5) | 0.872 |
| Coronary artery disease, n (%) | 28 (28.0) | 25 (29.8) | 3 (18.8) | 0.551 |
| Serum creatinine (mg/dl), n (%) | 0.8 (0.2) | 0.8 (0.2) | 0.8 (0.2) | 0.777 |
| Creatinine clearance by Cockcroft–Gault formula (ml/min) | 67 (52.7, 83.2) | 70 (56, 89.2) | 53.5 (48.2, 64) | 0.09 |
| Pre-existing pacemaker or defibrillator, n (%) | 11 (11.0) | 10 (11.9) | 1 (6.2) | 0.823 |
| History of right bundle-branch block, n (%) | 3 (3.0) | 2 (2.4) | 1 (6.2) | 0.972 |
| Treatment with vitamin K antagonist, n (%)c | 2 (2.0) | 2 (2.4) | 0 (0) | 0.996 |
| Treatment with direct oral anticoagulant, n (%)c | 5 (5.0) | 5 (6) | 0 (0) | 0.701 |
| Dual antiplatelets therapy, n (%)c | 23 (23.0) | 15 (26.8) | 8 (18.2) | 0.437 |
| Native bicuspid valve | 16 (16) | 0 | 16 (100) | |
| Type 0 Sievers | 2 (2) | 0 | 2 (12.5) | |
| Type I Sievers | 12 (12) | 0 | 12 (75) | |
| L-R rafe | 10 (83.3) | |||
| R-NC rafe | 1 (8.3) | |||
| L-NC rafe | 2 (16.6) | |||
| Symmetrical (160–180°) | 2 (16.6) | |||
| Asymmetrical (140–159°) | 3 (25) | |||
| Very asymmetrical (120–139°) | 5 (41.6) | |||
| Type II Sievers | 2 (2) | 0 | 2 (12.5) | |
| Aortic calcium score (AU) | 2878.4 (1650.4) | 2769.1 (1525.6) | 3031.5 (1879.7) | 0.08 |
| Evolut R 23 mm | 8 (8.0) | 8 (9.5) | 0 (0) | |
| Evolut R 26 mm | 44 (44.0) | 34 (40.5) | 10 (62.5) | |
| Evolut R 29 mm | 33 (33.0) | 29 (34.5) | 4 (25) | |
| Evolut R 34 mm | 15 (15.0) | 13 (15.5) | 2 (12.5) | |
| Pre-TAVI balloon valvuloplasty | 33 (33.0) | 24 (28.6) | 9 (56.2) | 0.065 |
| Post-TAVI balloon valvuloplasty | 49 (49.0) | 37 (44.0) | 12 (75.0) | 0.043 |
| Overall cohort (N = 100) | Native valve type | |||
|---|---|---|---|---|
| Tricuspid (N = 84) | Bicuspid (N = 16) | P-value | ||
| Age (year) | 78.2 (5.8) | 77.9 (5.9) | 79.6 (5.3) | 0.311 |
| BSAa (m2) | 1.7 (0.2) | 1.7 (0.2) | 1.6 (0.1) | 0.001 |
| BMIb | 27.8 (5.0) | 28.5 (5.0) | 24.6 (3.4) | 0.004 |
| Male sex, n (%) | 53 (53.0) | 45 (53.6) | 8.0 (50.0) | 0.992 |
| Euroscore II, % | 1.79 (1.5, 2.3) | 1.7 (1.5, 2.2) | 1.85 (1.4, 2.3) | 0.102 |
| Low flow—low gradient, n (%) | 11(11.0) | 10 (11.9) | 1 (6.2) | 0.825 |
| NYHA functional classes III–IV, n (%) | 13 (13.0) | 9.0 (10.7) | 4.0 (25.0) | 0.245 |
| NIDDM/IDDM, n (%) | 30 (30.0) | 27 (32.1) | 3 (18.8) | 0.439 |
| Hypertension, n (%) | 98 (98.0) | 82 (97.6) | 16 (100.0) | 0.991 |
| COPD, n (%) | 18 (18.0) | 14 (16.7) | 4 (25.0) | 0.660 |
| Previous stroke/TIA, n (%) | 4 (4.0) | 2 (2.4) | 2 (12.5) | 0.234 |
| Previous PCI, n (%) | 22 (22.0) | 19 (22.6) | 3 (18.8) | 0.983 |
| Previous cardiac surgery, n (%) | 9 (9.0) | 9 (10.7) | 0 (0) | 0.372 |
| Previous MI, n (%) | 17 (17.0) | 15 (17.9) | 2 (12.5) | 0.872 |
| Coronary artery disease, n (%) | 28 (28.0) | 25 (29.8) | 3 (18.8) | 0.551 |
| Serum creatinine (mg/dl), n (%) | 0.8 (0.2) | 0.8 (0.2) | 0.8 (0.2) | 0.777 |
| Creatinine clearance by Cockcroft–Gault formula (ml/min) | 67 (52.7, 83.2) | 70 (56, 89.2) | 53.5 (48.2, 64) | 0.09 |
| Pre-existing pacemaker or defibrillator, n (%) | 11 (11.0) | 10 (11.9) | 1 (6.2) | 0.823 |
| History of right bundle-branch block, n (%) | 3 (3.0) | 2 (2.4) | 1 (6.2) | 0.972 |
| Treatment with vitamin K antagonist, n (%)c | 2 (2.0) | 2 (2.4) | 0 (0) | 0.996 |
| Treatment with direct oral anticoagulant, n (%)c | 5 (5.0) | 5 (6) | 0 (0) | 0.701 |
| Dual antiplatelets therapy, n (%)c | 23 (23.0) | 15 (26.8) | 8 (18.2) | 0.437 |
| Native bicuspid valve | 16 (16) | 0 | 16 (100) | |
| Type 0 Sievers | 2 (2) | 0 | 2 (12.5) | |
| Type I Sievers | 12 (12) | 0 | 12 (75) | |
| L-R rafe | 10 (83.3) | |||
| R-NC rafe | 1 (8.3) | |||
| L-NC rafe | 2 (16.6) | |||
| Symmetrical (160–180°) | 2 (16.6) | |||
| Asymmetrical (140–159°) | 3 (25) | |||
| Very asymmetrical (120–139°) | 5 (41.6) | |||
| Type II Sievers | 2 (2) | 0 | 2 (12.5) | |
| Aortic calcium score (AU) | 2878.4 (1650.4) | 2769.1 (1525.6) | 3031.5 (1879.7) | 0.08 |
| Evolut R 23 mm | 8 (8.0) | 8 (9.5) | 0 (0) | |
| Evolut R 26 mm | 44 (44.0) | 34 (40.5) | 10 (62.5) | |
| Evolut R 29 mm | 33 (33.0) | 29 (34.5) | 4 (25) | |
| Evolut R 34 mm | 15 (15.0) | 13 (15.5) | 2 (12.5) | |
| Pre-TAVI balloon valvuloplasty | 33 (33.0) | 24 (28.6) | 9 (56.2) | 0.065 |
| Post-TAVI balloon valvuloplasty | 49 (49.0) | 37 (44.0) | 12 (75.0) | 0.043 |
Data were available for the entire cohort. Values are reported as the mean and standard deviation (SD), median interquartile range (IQR) or number and percentage (%).
AU: Agatston Units; BMI: body mass index; BSA: body surface area; COPD: chronic obstructive pulmonary disease; IDDM: insulin-dependent diabetes mellitus; L: left; MI: myocardial infarction; NC: non coronary; NIDDM: non-insulin dependent diabetes mellitus; NYHA: New York Heart Association; PCI: percutaneous coronary intervention; R: right; TIA: transient ischaemic attack; TAVI: transcatheter aortic valve implantation.
Body surface area was calculated with the Du Bois formula: 0.007 × weight0.425 × height0.725.
The body mass index was calculated as the weight in kilograms divided by the square of the height in meters.
At hospital discharge.
Characteristics of the patients at baseline and procedural details: tricuspid versus bicuspid group
| Overall cohort (N = 100) | Native valve type | |||
|---|---|---|---|---|
| Tricuspid (N = 84) | Bicuspid (N = 16) | P-value | ||
| Age (year) | 78.2 (5.8) | 77.9 (5.9) | 79.6 (5.3) | 0.311 |
| BSAa (m2) | 1.7 (0.2) | 1.7 (0.2) | 1.6 (0.1) | 0.001 |
| BMIb | 27.8 (5.0) | 28.5 (5.0) | 24.6 (3.4) | 0.004 |
| Male sex, n (%) | 53 (53.0) | 45 (53.6) | 8.0 (50.0) | 0.992 |
| Euroscore II, % | 1.79 (1.5, 2.3) | 1.7 (1.5, 2.2) | 1.85 (1.4, 2.3) | 0.102 |
| Low flow—low gradient, n (%) | 11(11.0) | 10 (11.9) | 1 (6.2) | 0.825 |
| NYHA functional classes III–IV, n (%) | 13 (13.0) | 9.0 (10.7) | 4.0 (25.0) | 0.245 |
| NIDDM/IDDM, n (%) | 30 (30.0) | 27 (32.1) | 3 (18.8) | 0.439 |
| Hypertension, n (%) | 98 (98.0) | 82 (97.6) | 16 (100.0) | 0.991 |
| COPD, n (%) | 18 (18.0) | 14 (16.7) | 4 (25.0) | 0.660 |
| Previous stroke/TIA, n (%) | 4 (4.0) | 2 (2.4) | 2 (12.5) | 0.234 |
| Previous PCI, n (%) | 22 (22.0) | 19 (22.6) | 3 (18.8) | 0.983 |
| Previous cardiac surgery, n (%) | 9 (9.0) | 9 (10.7) | 0 (0) | 0.372 |
| Previous MI, n (%) | 17 (17.0) | 15 (17.9) | 2 (12.5) | 0.872 |
| Coronary artery disease, n (%) | 28 (28.0) | 25 (29.8) | 3 (18.8) | 0.551 |
| Serum creatinine (mg/dl), n (%) | 0.8 (0.2) | 0.8 (0.2) | 0.8 (0.2) | 0.777 |
| Creatinine clearance by Cockcroft–Gault formula (ml/min) | 67 (52.7, 83.2) | 70 (56, 89.2) | 53.5 (48.2, 64) | 0.09 |
| Pre-existing pacemaker or defibrillator, n (%) | 11 (11.0) | 10 (11.9) | 1 (6.2) | 0.823 |
| History of right bundle-branch block, n (%) | 3 (3.0) | 2 (2.4) | 1 (6.2) | 0.972 |
| Treatment with vitamin K antagonist, n (%)c | 2 (2.0) | 2 (2.4) | 0 (0) | 0.996 |
| Treatment with direct oral anticoagulant, n (%)c | 5 (5.0) | 5 (6) | 0 (0) | 0.701 |
| Dual antiplatelets therapy, n (%)c | 23 (23.0) | 15 (26.8) | 8 (18.2) | 0.437 |
| Native bicuspid valve | 16 (16) | 0 | 16 (100) | |
| Type 0 Sievers | 2 (2) | 0 | 2 (12.5) | |
| Type I Sievers | 12 (12) | 0 | 12 (75) | |
| L-R rafe | 10 (83.3) | |||
| R-NC rafe | 1 (8.3) | |||
| L-NC rafe | 2 (16.6) | |||
| Symmetrical (160–180°) | 2 (16.6) | |||
| Asymmetrical (140–159°) | 3 (25) | |||
| Very asymmetrical (120–139°) | 5 (41.6) | |||
| Type II Sievers | 2 (2) | 0 | 2 (12.5) | |
| Aortic calcium score (AU) | 2878.4 (1650.4) | 2769.1 (1525.6) | 3031.5 (1879.7) | 0.08 |
| Evolut R 23 mm | 8 (8.0) | 8 (9.5) | 0 (0) | |
| Evolut R 26 mm | 44 (44.0) | 34 (40.5) | 10 (62.5) | |
| Evolut R 29 mm | 33 (33.0) | 29 (34.5) | 4 (25) | |
| Evolut R 34 mm | 15 (15.0) | 13 (15.5) | 2 (12.5) | |
| Pre-TAVI balloon valvuloplasty | 33 (33.0) | 24 (28.6) | 9 (56.2) | 0.065 |
| Post-TAVI balloon valvuloplasty | 49 (49.0) | 37 (44.0) | 12 (75.0) | 0.043 |
| Overall cohort (N = 100) | Native valve type | |||
|---|---|---|---|---|
| Tricuspid (N = 84) | Bicuspid (N = 16) | P-value | ||
| Age (year) | 78.2 (5.8) | 77.9 (5.9) | 79.6 (5.3) | 0.311 |
| BSAa (m2) | 1.7 (0.2) | 1.7 (0.2) | 1.6 (0.1) | 0.001 |
| BMIb | 27.8 (5.0) | 28.5 (5.0) | 24.6 (3.4) | 0.004 |
| Male sex, n (%) | 53 (53.0) | 45 (53.6) | 8.0 (50.0) | 0.992 |
| Euroscore II, % | 1.79 (1.5, 2.3) | 1.7 (1.5, 2.2) | 1.85 (1.4, 2.3) | 0.102 |
| Low flow—low gradient, n (%) | 11(11.0) | 10 (11.9) | 1 (6.2) | 0.825 |
| NYHA functional classes III–IV, n (%) | 13 (13.0) | 9.0 (10.7) | 4.0 (25.0) | 0.245 |
| NIDDM/IDDM, n (%) | 30 (30.0) | 27 (32.1) | 3 (18.8) | 0.439 |
| Hypertension, n (%) | 98 (98.0) | 82 (97.6) | 16 (100.0) | 0.991 |
| COPD, n (%) | 18 (18.0) | 14 (16.7) | 4 (25.0) | 0.660 |
| Previous stroke/TIA, n (%) | 4 (4.0) | 2 (2.4) | 2 (12.5) | 0.234 |
| Previous PCI, n (%) | 22 (22.0) | 19 (22.6) | 3 (18.8) | 0.983 |
| Previous cardiac surgery, n (%) | 9 (9.0) | 9 (10.7) | 0 (0) | 0.372 |
| Previous MI, n (%) | 17 (17.0) | 15 (17.9) | 2 (12.5) | 0.872 |
| Coronary artery disease, n (%) | 28 (28.0) | 25 (29.8) | 3 (18.8) | 0.551 |
| Serum creatinine (mg/dl), n (%) | 0.8 (0.2) | 0.8 (0.2) | 0.8 (0.2) | 0.777 |
| Creatinine clearance by Cockcroft–Gault formula (ml/min) | 67 (52.7, 83.2) | 70 (56, 89.2) | 53.5 (48.2, 64) | 0.09 |
| Pre-existing pacemaker or defibrillator, n (%) | 11 (11.0) | 10 (11.9) | 1 (6.2) | 0.823 |
| History of right bundle-branch block, n (%) | 3 (3.0) | 2 (2.4) | 1 (6.2) | 0.972 |
| Treatment with vitamin K antagonist, n (%)c | 2 (2.0) | 2 (2.4) | 0 (0) | 0.996 |
| Treatment with direct oral anticoagulant, n (%)c | 5 (5.0) | 5 (6) | 0 (0) | 0.701 |
| Dual antiplatelets therapy, n (%)c | 23 (23.0) | 15 (26.8) | 8 (18.2) | 0.437 |
| Native bicuspid valve | 16 (16) | 0 | 16 (100) | |
| Type 0 Sievers | 2 (2) | 0 | 2 (12.5) | |
| Type I Sievers | 12 (12) | 0 | 12 (75) | |
| L-R rafe | 10 (83.3) | |||
| R-NC rafe | 1 (8.3) | |||
| L-NC rafe | 2 (16.6) | |||
| Symmetrical (160–180°) | 2 (16.6) | |||
| Asymmetrical (140–159°) | 3 (25) | |||
| Very asymmetrical (120–139°) | 5 (41.6) | |||
| Type II Sievers | 2 (2) | 0 | 2 (12.5) | |
| Aortic calcium score (AU) | 2878.4 (1650.4) | 2769.1 (1525.6) | 3031.5 (1879.7) | 0.08 |
| Evolut R 23 mm | 8 (8.0) | 8 (9.5) | 0 (0) | |
| Evolut R 26 mm | 44 (44.0) | 34 (40.5) | 10 (62.5) | |
| Evolut R 29 mm | 33 (33.0) | 29 (34.5) | 4 (25) | |
| Evolut R 34 mm | 15 (15.0) | 13 (15.5) | 2 (12.5) | |
| Pre-TAVI balloon valvuloplasty | 33 (33.0) | 24 (28.6) | 9 (56.2) | 0.065 |
| Post-TAVI balloon valvuloplasty | 49 (49.0) | 37 (44.0) | 12 (75.0) | 0.043 |
Data were available for the entire cohort. Values are reported as the mean and standard deviation (SD), median interquartile range (IQR) or number and percentage (%).
AU: Agatston Units; BMI: body mass index; BSA: body surface area; COPD: chronic obstructive pulmonary disease; IDDM: insulin-dependent diabetes mellitus; L: left; MI: myocardial infarction; NC: non coronary; NIDDM: non-insulin dependent diabetes mellitus; NYHA: New York Heart Association; PCI: percutaneous coronary intervention; R: right; TIA: transient ischaemic attack; TAVI: transcatheter aortic valve implantation.
Body surface area was calculated with the Du Bois formula: 0.007 × weight0.425 × height0.725.
The body mass index was calculated as the weight in kilograms divided by the square of the height in meters.
At hospital discharge.
Post-implant prosthesis deformation
With regard to the entire cohort, the highest eccentricity was observed at the annulus level (index: 0.51 (SD: 0.11), while the lowest was observed at the outflow level (index: 0.22, SD: 0.14). The eccentricity index constantly decreased from the native annulus to the frame outflow (Fig. 4).
Post-implant prosthesis eccentricity; whole group, n = 100, mean eccentricity index: 0.38, SD: 0.08; tricuspid group, n = 84, mean eccentricity index: 0.37, SD: 0.08; bicuspid group, n = 16; mean eccentricity index: 0.43, SD: 0.09.
Mean eccentricity index was significantly higher in the bicuspid group (0.43, SD: 0.09, P = 0.005 vs 0.37, SD: 0.08 bicuspid vs tricuspid) and specifically there was higher prosthesis ellipticity in the bicuspid group at stent inflow, native annulus, leaflet inflow and waist level, compared to the tricuspid group (Table 2) (Supplementary Material, Fig. 4—Forest plot). There were no differences in commissural alignment, leaflet expansion, implantation depth and valve-to-coronary sinus distances between the 2 groups (Table 2) (Supplementary Material, Figs S2 and S3A–C).
Post-implant eccentricity and other prespecified MDCT measurements: Tricuspid vs Bicuspid groups
| Overall cohort (N = 100) | Native valve type | ||||
|---|---|---|---|---|---|
| Tricuspid (N = 84) | Bicuspid (N = 16) | P-value | MD (95% CI) | ||
| Eccentricity, mean SD | 0.38 (0.08) | 0.37 (0.08) | 0.43 (0.09) | 0.005 | |
| Frame inflow | 0.50 (0.14) | 0.49 (0.15) | 0.57 (0.13) | 0.023 | −0.08 (−015; −001) |
| Native annulus | 0.51 (0.11) | 0.51 (0.11) | 0.57 (0.13) | 0.034 | −0.06 (−013; 0.01) |
| Leaflet inflow | 0.47 (0.13) | 0.46 (0.13) | 0.53 (0.12) | 0.048 | −0.07 (−0.14; −0.00) |
| Prosthesis constrained—waist | 0.32 (0.15) | 0.31 (0.15) | 0.40 (0.14) | 0.025 | −0.09 (−0.17; −0.01) |
| Leaflet outflow | 0.22 (0.12) | 0.22 (0.12) | 0.26 (0.12) | 0.199 | −0.04 (−0.10; 0.02) |
| Frame outflow | 0.22 (0.14) | 0.22 (0.13) | 0.24 (0.17) | 0.612 | −0.02 (−0.11; 0.07) |
| Asymmetric leaflet expansion, degree, mean SD | 11.28 (6.18) | 11.35 (6.25) | 10.94 (5.94) | 0.810 | 0.41 (−2.79; 3.61) |
| Implantation depth, mm, mean SD | 5.92 (3.13) | 6.04 (3.21) | 5.28 (2.66) | 0.372 | 0.76 (−0.71; 2.23) |
| Commissural misalignment, n (%)a | 22 (22) | 20 (23.8) | 2 (12.5) | 0.683 | |
| Valve to coronary length, mm, mean SD | |||||
| Left coronary | 5.94 (1.91) | 5.85 (1.90) | 6.37 (1.98) | 0.327 | −0.52 (−1.57; 0.53) |
| Right coronary | 5.47 (2.10) | 5.61 (2.11) | 4.74 (1.92) | 0.134 | 0.87 (−0.17; 1.91) |
| Overall cohort (N = 100) | Native valve type | ||||
|---|---|---|---|---|---|
| Tricuspid (N = 84) | Bicuspid (N = 16) | P-value | MD (95% CI) | ||
| Eccentricity, mean SD | 0.38 (0.08) | 0.37 (0.08) | 0.43 (0.09) | 0.005 | |
| Frame inflow | 0.50 (0.14) | 0.49 (0.15) | 0.57 (0.13) | 0.023 | −0.08 (−015; −001) |
| Native annulus | 0.51 (0.11) | 0.51 (0.11) | 0.57 (0.13) | 0.034 | −0.06 (−013; 0.01) |
| Leaflet inflow | 0.47 (0.13) | 0.46 (0.13) | 0.53 (0.12) | 0.048 | −0.07 (−0.14; −0.00) |
| Prosthesis constrained—waist | 0.32 (0.15) | 0.31 (0.15) | 0.40 (0.14) | 0.025 | −0.09 (−0.17; −0.01) |
| Leaflet outflow | 0.22 (0.12) | 0.22 (0.12) | 0.26 (0.12) | 0.199 | −0.04 (−0.10; 0.02) |
| Frame outflow | 0.22 (0.14) | 0.22 (0.13) | 0.24 (0.17) | 0.612 | −0.02 (−0.11; 0.07) |
| Asymmetric leaflet expansion, degree, mean SD | 11.28 (6.18) | 11.35 (6.25) | 10.94 (5.94) | 0.810 | 0.41 (−2.79; 3.61) |
| Implantation depth, mm, mean SD | 5.92 (3.13) | 6.04 (3.21) | 5.28 (2.66) | 0.372 | 0.76 (−0.71; 2.23) |
| Commissural misalignment, n (%)a | 22 (22) | 20 (23.8) | 2 (12.5) | 0.683 | |
| Valve to coronary length, mm, mean SD | |||||
| Left coronary | 5.94 (1.91) | 5.85 (1.90) | 6.37 (1.98) | 0.327 | −0.52 (−1.57; 0.53) |
| Right coronary | 5.47 (2.10) | 5.61 (2.11) | 4.74 (1.92) | 0.134 | 0.87 (−0.17; 1.91) |
Values are reported as mean and standard deviation (SD), or number and percentage (%).
CI: confidence interval; MD: mean difference; MDCT: multi detector computed tomography.
Defined as at least moderate and an angle 30° signified an empirically set threshold for significant commissural misalignment.
Post-implant eccentricity and other prespecified MDCT measurements: Tricuspid vs Bicuspid groups
| Overall cohort (N = 100) | Native valve type | ||||
|---|---|---|---|---|---|
| Tricuspid (N = 84) | Bicuspid (N = 16) | P-value | MD (95% CI) | ||
| Eccentricity, mean SD | 0.38 (0.08) | 0.37 (0.08) | 0.43 (0.09) | 0.005 | |
| Frame inflow | 0.50 (0.14) | 0.49 (0.15) | 0.57 (0.13) | 0.023 | −0.08 (−015; −001) |
| Native annulus | 0.51 (0.11) | 0.51 (0.11) | 0.57 (0.13) | 0.034 | −0.06 (−013; 0.01) |
| Leaflet inflow | 0.47 (0.13) | 0.46 (0.13) | 0.53 (0.12) | 0.048 | −0.07 (−0.14; −0.00) |
| Prosthesis constrained—waist | 0.32 (0.15) | 0.31 (0.15) | 0.40 (0.14) | 0.025 | −0.09 (−0.17; −0.01) |
| Leaflet outflow | 0.22 (0.12) | 0.22 (0.12) | 0.26 (0.12) | 0.199 | −0.04 (−0.10; 0.02) |
| Frame outflow | 0.22 (0.14) | 0.22 (0.13) | 0.24 (0.17) | 0.612 | −0.02 (−0.11; 0.07) |
| Asymmetric leaflet expansion, degree, mean SD | 11.28 (6.18) | 11.35 (6.25) | 10.94 (5.94) | 0.810 | 0.41 (−2.79; 3.61) |
| Implantation depth, mm, mean SD | 5.92 (3.13) | 6.04 (3.21) | 5.28 (2.66) | 0.372 | 0.76 (−0.71; 2.23) |
| Commissural misalignment, n (%)a | 22 (22) | 20 (23.8) | 2 (12.5) | 0.683 | |
| Valve to coronary length, mm, mean SD | |||||
| Left coronary | 5.94 (1.91) | 5.85 (1.90) | 6.37 (1.98) | 0.327 | −0.52 (−1.57; 0.53) |
| Right coronary | 5.47 (2.10) | 5.61 (2.11) | 4.74 (1.92) | 0.134 | 0.87 (−0.17; 1.91) |
| Overall cohort (N = 100) | Native valve type | ||||
|---|---|---|---|---|---|
| Tricuspid (N = 84) | Bicuspid (N = 16) | P-value | MD (95% CI) | ||
| Eccentricity, mean SD | 0.38 (0.08) | 0.37 (0.08) | 0.43 (0.09) | 0.005 | |
| Frame inflow | 0.50 (0.14) | 0.49 (0.15) | 0.57 (0.13) | 0.023 | −0.08 (−015; −001) |
| Native annulus | 0.51 (0.11) | 0.51 (0.11) | 0.57 (0.13) | 0.034 | −0.06 (−013; 0.01) |
| Leaflet inflow | 0.47 (0.13) | 0.46 (0.13) | 0.53 (0.12) | 0.048 | −0.07 (−0.14; −0.00) |
| Prosthesis constrained—waist | 0.32 (0.15) | 0.31 (0.15) | 0.40 (0.14) | 0.025 | −0.09 (−0.17; −0.01) |
| Leaflet outflow | 0.22 (0.12) | 0.22 (0.12) | 0.26 (0.12) | 0.199 | −0.04 (−0.10; 0.02) |
| Frame outflow | 0.22 (0.14) | 0.22 (0.13) | 0.24 (0.17) | 0.612 | −0.02 (−0.11; 0.07) |
| Asymmetric leaflet expansion, degree, mean SD | 11.28 (6.18) | 11.35 (6.25) | 10.94 (5.94) | 0.810 | 0.41 (−2.79; 3.61) |
| Implantation depth, mm, mean SD | 5.92 (3.13) | 6.04 (3.21) | 5.28 (2.66) | 0.372 | 0.76 (−0.71; 2.23) |
| Commissural misalignment, n (%)a | 22 (22) | 20 (23.8) | 2 (12.5) | 0.683 | |
| Valve to coronary length, mm, mean SD | |||||
| Left coronary | 5.94 (1.91) | 5.85 (1.90) | 6.37 (1.98) | 0.327 | −0.52 (−1.57; 0.53) |
| Right coronary | 5.47 (2.10) | 5.61 (2.11) | 4.74 (1.92) | 0.134 | 0.87 (−0.17; 1.91) |
Values are reported as mean and standard deviation (SD), or number and percentage (%).
CI: confidence interval; MD: mean difference; MDCT: multi detector computed tomography.
Defined as at least moderate and an angle 30° signified an empirically set threshold for significant commissural misalignment.
Valvular and perivalvular thrombosis
Among the 100 patients with evaluable MDCT scans at 6 months, 44 (44%) had thrombus at any aortic valve complex (Fig. 5A–C). Leaflet thrombosis was detected in 18 (18%) patients; 6 (6%) had at least 1 leaflet with severe thrombosis (Supplementary Material, Fig. 4). Breakdown of the extent of HALT and RELM is presented in Supplementary Material, Table S1). Subvalvular thrombosis with partial or complete circumferential involvement of the prosthesis inner skirt was diagnosed in 23 patients (23%) (Supplementary Material, Fig. 5A–C). Thrombosis of the anatomic sinus was detected in 24 patients (24%) and was more prevalent in the non-coronary sinus (Supplementary Material, Fig. 6A–C). Valvular and perivalvular thrombosis were significantly more frequent in the bicuspid group than in the tricuspid group (81% vs 36.9%, P = 0.031); specifically, 10 out of 16 patients had HALT/SLT in the bicuspid group (62.5%) than in 8 out of 84 patients in the tricuspid group (9.5%), P < 0.001; sinus thrombosis was also more frequent in the bicuspid group than in the tricuspid group (P = 0.019), while there was no difference with regard to subvalvular thrombosis (Supplementary Material, Table S1).
(A) Leaflet thrombosis; (B) subvalvular thrombosis; (C) anatomic sinus thrombosis. Left panel, yellow asterisk indicates bicuspid valve; middle panel, blue arrow indicates thrombosis, right panel red lines indicate long and short prosthesis axis and serve as indicator of prosthesis deformation.
Prosthesis function analysis
Echocardiographic characteristics at baseline, discharge and 6 months follow-up are shown in Supplementary Material, Table S2. There was a significantly higher mean gradient at baseline in the bicuspid group compared to tricuspid (46.18, SD: 10.86 mmHg vs 57.53, SD: 19.52 mmHg, P = 0.034, tricuspid vs bicuspid group, respectively). At follow-up the mean aortic valve gradient after TAVI remained low, with no significant difference between the tricuspid and bicuspid groups (7.09, SD: 3.05 mmHg vs 7.31, SD: 5.53 mmHg, P = 0.825).
In the 2 patients with severe RELM (>50%, 1 leaflet), the mean gradients were 14 and 20 mmHg, respectively, and the latter (with native bicuspid valve) was the only patient in whom an haemodynamic structural valve definition diagnosis was made because of a concomitant decrease in effective orifice area ≥0.3 cm2 (Supplementary Material, Tables S1 and S2). At 6-month follow-up, EOAi was similar between the tricuspid and bicuspid groups (1.03, SD: 0.13 cm2 vs 1.08, SD: 0.12 cm2, P = 0.101) (mixed model, P = 0.763), with no significant changes compared to discharge (Supplementary Material, Fig. S7A–F). Bioprosthetic valve dysfunction diagnosis (haemodynamic and non-structural definition) was reached in 13 (15.5%) and 4 (25%) patients in the tricuspid and bicuspid groups, respectively (P = 0.576).
Clinical outcome
Clinical outcomes are shown in Supplementary Material, Table S3. Seven patients were discharged on oral anticoagulants; during follow-up, 2 more patients were started on anticoagulants for episodes of atrial fibrillation. At the time of MDCT scan 18 patients were receiving dual antiplatelet therapy. In the tricuspid group, 1 episode of acute coronary syndrome caused by a fresh thrombus at the level of the right coronary artery treated with coronary angioplasty occurred 2 days after the index procedure. Later, MDCT revealed the presence of a thrombus at the level of the right and non-coronary sinus. Overall, 5 episodes of transient ischaemic attack occurred during follow-up (2 in the group with native bicuspid valve), with no sequelae. Notably, there was a significantly higher risk of adverse events (neurological events and procedure-related or valve-related hospitalization) in the bicuspid compared to the tricuspid group (HR : 3.72, 95% CI: 1.07–13.4, log-rank test P = 0.027) (Supplementary Material, Table 3 and Fig. S8).
DISCUSSION
With this study based on the analysis of 100 post-implant MDCT scans and 2D transthoracic echocardiography at the 6-month follow-up, we were able to demonstrate that prosthesis deformation was more often observed in the group with native bicuspid valve stenosis, along with a higher incidence of valvular and perivalvular thrombosis.
While echocardiographic performance was not compromised, bicuspid native valve stenosis was associated with a significantly higher risk of adverse events (neurological events and procedure-related or valve-related hospitalization) at early follow-up.
There is little evidence of post-implant MDCT analysis in the context of self-expandable prostheses, such as Evolut R [4, 14]; furthermore, there are limited data on prosthesis expansion and deformation in the context of native bicuspid valve stenosis [14]. TAVI for bicuspid aortic stenosis remains challenging and may be associated with suboptimal results at follow-up [2].
Theoretically, anatomical derangement from normal post-implant prosthesis geometry may affect valve performance, disrupt laminar blood flow patterns, alter force distribution across the leaflets and their attachments and predispose to thrombus formation [14, 18, 19].
‘Stent-frame decoupling’ refers to a condition in which the lowest segments of the valve conform and adapt to the left ventricle outflow tract and native annular level (where more eccentricity is expected), whereas the highest segments maintain a more circular and symmetric shape [4]. This phenomenon is possible because of the supravalvular conformation of self-expandable valves and should result in the preservation of prosthesis leaflets symmetry while maximizing performance [4]. While our study was limited by the relatively low number of patients with bicuspid valves, it allowed us to demonstrate that, conversely to the tricuspid group, a high level of eccentricity remained in most prosthetic segments analysed.
Early MDCT assessment of post-implant geometry, although not recommended if not clinically indicated, can be informative because it can identify early signs of prosthesis degeneration (i.e. HALT/SLT and perivalvular thrombosis) that are generally not visible with 2D transthoracic echocardiography [8]; importantly, leaflet thrombosis is a dynamic process that can be reversed at early stage by oral anticoagulation therapy [8, 20].
In our series, we were able to confirm that thrombus stratification could be identified not only at the valvular level (i.e. leaflets) but also at the perivalvular (i.e. inner skirt and anatomic sinus) levels, and these findings were more frequent in the bicuspid group. None of the bicuspid patients were on oral anticoagulants and only 2 were taking dual antiplatelet therapy at the time of the MDCT scan. Hence, the role of anticoagulants requires further assessment, particularly in young patients with a low risk of bleeding [8].
The risk of adverse events at follow-up was significantly higher in the bicuspid group than that in the tricuspid group. In the bicuspid group, 4 events (2 transient ischaemic attacks, 1 re-hospitalization for heart failure, and 1 late pacemaker insertion) were recorded. The association between HALT/SLT and an increased risk of neurological events has been previously described [20].
TAVI is nowadays considered a solid alternative to conventional surgery for the treatment of aortic valve stenosis and a therapeutic option for younger patients at low risk for surgery with bicuspid valve [1, 21]; prosthesis durability and performance must be carefully evaluated since these patients have longer life expectancy.
This study has limitations; perhaps the chief limitation lies in the limited sample, and only 2 patients had a type 0 bicuspid valve according to the Sievers classification. Notably, a sample size estimation was not calculated in advanced. Also, follow-up was limited to 6-month time that represents a limited window to assess for SVD; however, very few studies have investigated self-expandable valves with MDCT beyond the 30-days follow-up [8]. It is worth to notice that this study with regard to the time-to-event analysis included highly selected cohort of patients, hence final conclusion cannot be drawn. In deep regression analysis to investigate predictors of thrombosis was not carried out, nor tricuspid and bicuspid group were adjusted for confounders. While the calcium score did not differ between tricuspid and bicuspid valves, other key elements such as calcium distribution or calcium volume and morphology were not evaluated; further analysis should consider these factors in relation to eccentricity, prosthesis deformation and HALT/SLT.
Many patients with atrial fibrillation with indications for oral anticoagulants were excluded because of poorly controlled heart rhythm. Echocardiograms were obtained by different operators; hence, a certain degree of inter-operator variability cannot be ruled out.
CONCLUSION
In conclusion, prosthesis deformation often occurs in bicuspid aortic valve stenosis, which may lead to a higher incidence of valvular and perivalvular thrombosis and suboptimal outcome even at early follow-up.
SUPPLEMENTARY MATERIAL
Supplementary material is available at EJCTS online.
FUNDING
This research was funded by a European grant (PO-FESR 2014–2020).
Conflict of interest: Lakshmi Dasi: Stakeholder in Dasi Simulations. All the other authors and study collaborators have no conflict of interest to declare.
DATA AVAILABILITY
The data underlying this article will be shared on reasonable request to the corresponding author.
Author contributions
Marco Moscarelli: Conceptualization; Data curation; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Supervision; Visualization; Writing—original draft; Writing—review & editing. Aniket Venkatesh: Data curation; Formal analysis; Investigation; Project administration; Resources; Software; Visualization; Writing—original draft. Katelynne Berland: Formal analysis; Investigation; Methodology; Software; Validation. Breandan Yeats: Data curation; Formal analysis; Investigation; Software; Visualization; Writing—original draft. Taylor Becker: Data curation; Resources; Software; Visualization; Writing—review & editing. Gregorio Zaccone: Conceptualization; Data curation; Investigation; Methodology; Resources; Visualization. Vincenzo Pernice: Conceptualization; Data curation; Investigation; Methodology; Project administration; Resources. Sabrina Milo: Methodology; Project administration; Software; Validation; Visualization. Adriana Zlahoda-Huzior: Software; Visualization; Writing—original draft; Writing—review & editing. Dariusz Dudek: Conceptualization; Funding acquisition; Investigation; Methodology; Project administration. Francesca Trizzino: Project administration; Resources; Software. Giuseppe Speziale: Funding acquisition; Methodology; Project administration. Lakshmi Prasad Dasi: Conceptualization; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Resources; Software; Supervision; Validation; Visualization. Khalil Fattouch: Conceptualization; Data curation; Funding acquisition; Investigation; Methodology; Project administration; Supervision; Visualization; Writing—review & editing.
Reviewer information
European Journal of Cardio-Thoracic Surgery thanks Amedeo Anselmi, Omar A. Jarral, Daniel-Sebastian Dohle, Chris M. Feindel and the other, anonymous reviewers for their contribution to the peer review process of this article.
REFERENCES
ABBREVIATIONS
- MDCT
Multi detector computed tomography
- RELM
Restricted leaflet motion
- SLT
Subclinical leaflet thrombosis
- TAVI
Transcatheter aortic valve implantation
