Balloon-expandable transapical transcatheter aortic valve implantation with or without predilation of the aortic valve: results of a multicentre registry

Balloon-expandable transapical transcatheter aortic valve implantation with or without... Abstract OBJECTIVES To assess safety and efficacy of transapical transcatheter aortic valve implantation (TA-TAVI) in the absence of predilation using balloon aortic valvuloplasty (BAV). Predilation of the stenosed valve using BAV is a routine step in TA-TAVI; however, evidence supporting its clinical value is lacking, and several studies have linked it with higher complication rates. METHODS A prospective, two-armed, multicentre registry (EASE-IT TA) to gather data on patients undergoing TA-TAVI with or without BAV, using the Edwards SAPIEN 3 valve was designed. The primary evaluation criterion was a composite of all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, acute kidney injury and pacemaker implantation [per Valve Academic Research Consortium-2 (VARC-2)] within 30 days after TAVI. RESULTS A total of 198 subjects underwent TA-TAVI, 61 with and 137 without BAV. Patient characteristics were comparable at baseline (mean ± SD: age 80.3 ± 5.7 years; logistic EuroSCORE 20.2 ± 12.6). Similar reductions in peak and mean transvalvular gradients were observed post-procedurally. There was a significant reduction of fluoroscopy time without BAV (4.7 vs 7.9 min; P = 0.039) and significantly decreased odds of catecholamine administration (17.5% vs 32.8%; P = 0.017). A decreased odds of the primary evaluation criterion in patients without BAV after 30 days (adjusted odds ratio 0.71; 95% confidence interval 0.34–1.82) and the same composite end-point after 6 months (adjusted odds ratio 0.74; 95% confidence interval 0.37–1.47) were not significant even after multivariable adjustment. CONCLUSIONS TA-TAVI without BAV appears to be at least equal to its conventional counterpart in terms of efficacy and may offer advantages in terms of safety. Thus, there appears to be little justification for maintaining the BAV step in TA-TAVI for many patients. EASE-IT, Transapical, Transcatheter aortic valve implantation, Balloon aortic valvuloplasty INTRODUCTION Dilation of the aortic valve using an expandable balloon [balloon aortic valvuloplasty (BAV)] has previously been considered an obligatory step for preparing the landing zone prior to deployment of the transcatheter heart valve (THV) in transcatheter aortic valve implantation (TAVI). This step provides an opportunity to assess the dimensions of the native valve, evaluate the risk for coronary occlusion and examine the potential for ‘balloon jump’ [1]. However, BAV is also associated with several serious complications, including haemodynamic failure, arrhythmia, atrioventricular block, systemic embolism, myocardial infarction (MI) and bleeding following cardiac perforation or trauma-mediated aortic root rupture [2]. Considering that these complications are potentially life-threatening, omission of BAV from the TAVI procedure has become increasingly popular among physicians [3–5]. The clinical value of TAVI without BAV has principally been investigated in the context of transfemoral (TF)-TAVI. Results from these studies have been encouraging, with reported technical success rates ranging from 85% to 96.7% [3, 4, 6–8] and procedural-related mortality rates between 2.5% and 7.7% [3, 4, 7–9]. Indeed, recent publications have reported the superiority of TF-TAVI without BAV over with BAV in terms of incidence of paravalvular leakage (PVL) [6, 8], procedural times [8, 9], fluoroscopy times [8], contrast agent volumes [6, 8, 10], rates of permanent pacemaker implantation (PPI) and 30-day mortality [9]. However, to our knowledge, only 1 article has been published regarding transapical (TA)-TAVI with an Edwards SAPIEN valve without BAV and was a pilot study involving just 6 patients [5]. The authors reported successful deployment in 100% of patients, accompanied by shorter procedural durations, decreased radiation exposure and reduced contrast agent volumes. They also proposed that TA-TAVI without BAV may reduce the probability of haemodynamic instability in patients with a diminished left ventricular ejection fraction. Clearly, larger comparative studies are required to further clarify the potential risks and benefits associated with eliminating the BAV step from the TA-TAVI procedure. Consequently, we designed a prospective, two-armed, multicentre registry (EASE-IT TA) to gather real-world data on patients undergoing TA-TAVI using the Edwards SAPIEN 3 THV, either with or without BAV. The data gathered on procedural aspects, efficacy and safety outcomes for each group of patients were compared, with the aim of clarifying the clinical value of the BAV step and the safety advantages, if any, of omitting it. MATERIALS AND METHODS The EASE-IT TA is a multicentre, prospective, two-armed, observational registry, established between April 2014 and February 2016. Prior ethical approval was obtained from the relevant ethics committees at each site. Only patients providing written informed consent were included. Design and study participants The design and rationale for the EASE-IT TA has previously been described [11]. Briefly, subjects were recruited from 10 German sites with appropriate training in the use of the Edwards SAPIEN 3 and the Ascendra Balloon Catheter (Edwards Lifesciences, Irvine, CA, USA) and prior experience of at least 20 TA-TAVI implantations. Patients aged 18 years or older with an indication for TAVI according to the Edwards SAPIEN 3 instructions (both with and without BAV) were eligible for study inclusion. Patients with a logistic EuroSCORE >50%, mitral or tricuspid valvular insufficiency >Grade II, previous aortic valve replacement, uncontrolled atrial fibrillation, left ventricular or atrial thrombus, recent cerebrovascular event, a high probability of non-adherence to follow-up or for whom the use of the Edwards SAPIEN 3 or the Ascendra Balloon Catheter was contraindicated based on instructions for use were excluded. At each site, the decision for a patient to receive TA-TAVI with or without BAV was made by their treating physician prior to enrolment in the study and was independent from the registry. TA access was selected according to patient characteristics, as well as physician preference, and the standard practice at each site. BAV was performed at the discretion of the treating physician. TA-TAVI with BAV was performed as described by Walther et al. [1], while that without BAV was carried out in a similar manner to that suggested by Wendler et al. [5]. Following study completion, 20% of participating sites underwent source data verification to ensure data validity. Study objectives The primary objective was to determine clinical safety as a composite evaluation of events (all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and PPI), which occurred up to 30 days after TA-TAVI. These events were defined per the Valve Academic Research Consortium-2 (VARC-2) consensus document [12]. Secondary objectives were to determine the rates of each of these events considered individually, periprocedural data (procedural duration, duration of radiation exposure, volume of contrast agent used and aortic root rupture), PVL, change in peak and mean transvalvular gradients post-TAVI and change in New York Heart Association (NYHA) class at 30-day follow-up relative to baseline. Statistical analysis The sample size for EASE-IT was established based on the previously reported event rates and the feasibility to detect an absolute risk reduction for the primary evaluation criterion of 13% at 30 days while taking into consideration a 10% dropout rate [11]. Under these assumptions, the power of the registry was 80%. However, based on the real-world nature of such registries, there was an unequal recruitment into the patient groups, resulting in 61 patients with and 137 patients without BAV. Data for the groups that underwent TA-TAVI with BAV were compared to those without BAV on an intention-to-treat basis using descriptive data analysis. Categorical variables were presented as frequency distributions, while continuous variables were reported as median (range) or mean ± standard deviation, as appropriate. Groups were tested for equal distribution in baseline variables by χ2 test for dichotomuous variables and by the t-test for continuous variables. The odds ratio (OR) for events occurring by 30-day follow-up in the 2 groups was calculated using a logistic model, which included age, gender, left ventricular ejection fraction, previous MI, stroke/transient ischaemic attack, prior PPI, creatinine ≥2.0 mg/dl, and NYHA Class III/IV as covariables using the Firth penalized maximum likelihood estimation to reduce bias in the parameter estimates because of the low number of events in some end-points. Unadjusted ORs were calculated from frequency tables. Data were analysed using Statistical Analysis System (SAS) version 9.3 (SAS Institute Inc., Cary, NC, USA). RESULTS Of the 200 patients originally enrolled in the registry, 2 were excluded due to duplication (Fig. 1). Of the remaining 198 patients, 61 underwent TA-TAVI with BAV, while 137 underwent TA-TAVI without BAV. Figure 1: View largeDownload slide Patient flow. BAV: balloon aortic valvuloplasty; 30d: thirty days; FU: follow-up; 6 mo: 6 months. Figure 1: View largeDownload slide Patient flow. BAV: balloon aortic valvuloplasty; 30d: thirty days; FU: follow-up; 6 mo: 6 months. Patient characteristics When comparing the baseline characteristics of the with BAV group to the without BAV group, no significant differences were observed for any of the documented factors, which included age, female gender, body mass index, prevalence of comorbidities, history of cardiac events and aortic stenosis-related parameters (Table 1). Although not statistically different, a lower mean logistic EuroSCORE was seen for patients in the with BAV group compared to the without BAV group (17.6% vs 21.6%; P = 0.081). Table 1: Patient baseline characteristics and aortic stenosis-related parameters at baseline   Total (N = 198)  TAVI with BAV (N = 61)  TAVI without BAV (N = 137)  P-value  Age (years), mean ± SD  80.3 ± 5.7  80.5 ± 5.4  80.2 ± 5.9  0.762a  Female gender, n/N (%)  81/198 (40.9)  25/61 (41.0)  56/137 (40.9)  0.989  Body mass index (kg/m2), mean ± SD  27.0 ± 4.4  27.4 ± 5.0  26.9 ± 4.1  0.448a  Comorbidity, n/N (%)           Hypertension  186/198 (93.9)  59/61 (96.7)  127/137 (92.7)  0.274   Diabetes  75/198 (37.9)  27/61 (44.3)  48/137 (35.0)  0.217   Stroke/TIA  30/198 (15.2)  10/61 (16.4)  20/137 (14.6)  0.745   PAD  77/198 (38.9)  28/61 (45.9)  49/137 (35.8)  0.177   Pulmonary hypertension  23/197 (11.7)  7/61 (11.5)  16/136 (11.8)  0.953   Creatinine ≥2.0 mg/dl  10/198 (5.1)  3/61 (4.9)  7/137 (5.1)  1.000   Dialysis  3/198 (1.5)  2/61 (3.3)  1/137 (0.7)  0.175  Cardiac history, n/N (%)           CAD  128/198 (64.7)  36/61 (59.0)  92/137 (67.2)  0.269   Prior MI  21/198 (10.6)  6/61 (9.8)  15/137 (10.9)  0.814   Prior CV intervention  97/198 (49.0)  26/61 (42.6)  71/137 (51.8)  0.232   Prior pacemaker/ICD  28/198 (14.1)  8/61 (13.1)  20/137 (14.6)  0.782  Logistic EuroSCORE I (%), mean ± SD  20.2 ± 12.6  17.6 ± 10.2  21.6 ± 13.6  0.081a  Echocardiography of the aortic valve, mean ± SD           Peak gradient (mmHg)  67.9 ± 22.2  70.0 ± 21.4  66.8 ± 22.6  0.386a   Mean gradient (mmHg)  41.6 ± 13.6  43.1 ± 14.9  40.9 ± 12.9  0.317a   Vmax (m/s)  4.0 ± 1.2  4.0 ± 1.2  4.0 ± 1.2  0.958a  LVEF (%), mean ± SD  52.2 ± 12.8  54.1 ± 11.3  51.3 ± 13.4  0.159a  NYHA Class III/IV, n/N (%)  169/198 (85.4)  52/61 (85.2)  117/137 (85.4)  0.977  CCS Class III/IV, n/N (%)  42/197 (21.3)  14/61 (23.0)  28/136 (20.6)  0.708  Syncope, n/N (%)  20/198 (10.1)  4/61 (6.6)  16/137 (11.7)  0.270  Dizziness with exertion, n/N (%)  25/198 (12.6)  8/61 (13.1)  17/137 (12.4)  0.890    Total (N = 198)  TAVI with BAV (N = 61)  TAVI without BAV (N = 137)  P-value  Age (years), mean ± SD  80.3 ± 5.7  80.5 ± 5.4  80.2 ± 5.9  0.762a  Female gender, n/N (%)  81/198 (40.9)  25/61 (41.0)  56/137 (40.9)  0.989  Body mass index (kg/m2), mean ± SD  27.0 ± 4.4  27.4 ± 5.0  26.9 ± 4.1  0.448a  Comorbidity, n/N (%)           Hypertension  186/198 (93.9)  59/61 (96.7)  127/137 (92.7)  0.274   Diabetes  75/198 (37.9)  27/61 (44.3)  48/137 (35.0)  0.217   Stroke/TIA  30/198 (15.2)  10/61 (16.4)  20/137 (14.6)  0.745   PAD  77/198 (38.9)  28/61 (45.9)  49/137 (35.8)  0.177   Pulmonary hypertension  23/197 (11.7)  7/61 (11.5)  16/136 (11.8)  0.953   Creatinine ≥2.0 mg/dl  10/198 (5.1)  3/61 (4.9)  7/137 (5.1)  1.000   Dialysis  3/198 (1.5)  2/61 (3.3)  1/137 (0.7)  0.175  Cardiac history, n/N (%)           CAD  128/198 (64.7)  36/61 (59.0)  92/137 (67.2)  0.269   Prior MI  21/198 (10.6)  6/61 (9.8)  15/137 (10.9)  0.814   Prior CV intervention  97/198 (49.0)  26/61 (42.6)  71/137 (51.8)  0.232   Prior pacemaker/ICD  28/198 (14.1)  8/61 (13.1)  20/137 (14.6)  0.782  Logistic EuroSCORE I (%), mean ± SD  20.2 ± 12.6  17.6 ± 10.2  21.6 ± 13.6  0.081a  Echocardiography of the aortic valve, mean ± SD           Peak gradient (mmHg)  67.9 ± 22.2  70.0 ± 21.4  66.8 ± 22.6  0.386a   Mean gradient (mmHg)  41.6 ± 13.6  43.1 ± 14.9  40.9 ± 12.9  0.317a   Vmax (m/s)  4.0 ± 1.2  4.0 ± 1.2  4.0 ± 1.2  0.958a  LVEF (%), mean ± SD  52.2 ± 12.8  54.1 ± 11.3  51.3 ± 13.4  0.159a  NYHA Class III/IV, n/N (%)  169/198 (85.4)  52/61 (85.2)  117/137 (85.4)  0.977  CCS Class III/IV, n/N (%)  42/197 (21.3)  14/61 (23.0)  28/136 (20.6)  0.708  Syncope, n/N (%)  20/198 (10.1)  4/61 (6.6)  16/137 (11.7)  0.270  Dizziness with exertion, n/N (%)  25/198 (12.6)  8/61 (13.1)  17/137 (12.4)  0.890  a t-test was used to calculate P-values; categorical variables were analysed using the χ2 test. BAV: balloon aortic valvuloplasty; CAD: coronary artery disease; CCS: Canadian Cardiovascular Society; CV: cardiovascular; ICD: implantable cardioverter defibrillator; LVEF: left ventricular ejection fraction; MI: myocardial infraction; NYHA: New York Heart Association; PAD: peripheral artery disease; SD: standard deviation; TAVI: transcatheter aortic valve implantation; TIA: transient ischaemic attack; Vmax: maximum velocity. Procedural details Of the patients who underwent TA-TAVI with BAV, the majority underwent the predilation using a 20-mm balloon (80.7%) (Table 2). The most common valve implanted was the 26 mm (49.2% and 40.9% of the with BAV and without BAV patients, respectively). The proportion of patients requiring balloon post-dilation was slightly higher in the group with BAV (14.8%) compared to without (9.5%) TA-TAVI groups, though no statistically significant difference was detected. Table 2: Procedural details and outcomes of TA-TAVI   Total (N = 198)  TAVI with BAV (N = 61)  TAVI without BAV (N = 137)  P-value  Size of balloon used for predilation, n/N (%)  61/198 (30.8)  61/61 (100.0)  n.a.  n.a.   20 mm  46/194 (23.7)  46/57 (80.7)  n.a.  n.a.   22/23 mm  5/194 (2.6)  5/57 (8.8)  n.a.  n.a.   25/26 mm  6/194 (3.1)  6/57 (10.5)  n.a.  n.a.  Size of implanted THV, n/N (%)        0.470   23 mm  60/198 (30.3)  18/61 (29.5)  42/137 (30.7)     26 mm  86/198 (43.4)  30/61 (49.2)  56/137 (40.9)     29 mm  52/198 (26.3)  13/61 (21.3)  39/137 (28.5)    Requirement for balloon post-dilation, n/N (%)  22/198 (11.1)  9/61 (14.8)  13/137 (9.5)  0.276  Procedural characteristics, median (1st–3rd quartile)           Procedural duration (min)  76 (58–98)  85 (63–104)  74.5 (58.0–96.5)  0.295   Fluoroscopy time (min)  4 (3–6)  5 (4–6)  4 (3–5)  0.039   Contrast agent volume (ml)  80 (60–100)  85 (60–108)  80 (60–100)  0.965  Procedural complications, n/N (%)           Access complicationsa  1/198 (0.5)  0/61 (0)  1/137 (0.7)  0.504   Hemodynamic instability  10/198 (5.1)  4/61 (6.6)  6/137 (4.4)  0.518   Catecholamine use  44/198 (22.2)  20/61 (32.8)  24/137 (17.5)  0.017  Procedural result, n/N (%)           Device successb  198/198 (100)  61/61 (100)  137/137 (100)  n.a.   Device failurec            Mortality  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Second valve used  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Conversion to surgery  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Device malfunction  1/198 (0.5)  0/61 (0)  1/137 (0.7)  0.504   Other events, n/N (%)            Complete AV block with PPI  3/198 (1.5)  1/61 (1.6)  2/137 (1.5)  1.000    Aortic root rupture  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Total (N = 198)  TAVI with BAV (N = 61)  TAVI without BAV (N = 137)  P-value  Size of balloon used for predilation, n/N (%)  61/198 (30.8)  61/61 (100.0)  n.a.  n.a.   20 mm  46/194 (23.7)  46/57 (80.7)  n.a.  n.a.   22/23 mm  5/194 (2.6)  5/57 (8.8)  n.a.  n.a.   25/26 mm  6/194 (3.1)  6/57 (10.5)  n.a.  n.a.  Size of implanted THV, n/N (%)        0.470   23 mm  60/198 (30.3)  18/61 (29.5)  42/137 (30.7)     26 mm  86/198 (43.4)  30/61 (49.2)  56/137 (40.9)     29 mm  52/198 (26.3)  13/61 (21.3)  39/137 (28.5)    Requirement for balloon post-dilation, n/N (%)  22/198 (11.1)  9/61 (14.8)  13/137 (9.5)  0.276  Procedural characteristics, median (1st–3rd quartile)           Procedural duration (min)  76 (58–98)  85 (63–104)  74.5 (58.0–96.5)  0.295   Fluoroscopy time (min)  4 (3–6)  5 (4–6)  4 (3–5)  0.039   Contrast agent volume (ml)  80 (60–100)  85 (60–108)  80 (60–100)  0.965  Procedural complications, n/N (%)           Access complicationsa  1/198 (0.5)  0/61 (0)  1/137 (0.7)  0.504   Hemodynamic instability  10/198 (5.1)  4/61 (6.6)  6/137 (4.4)  0.518   Catecholamine use  44/198 (22.2)  20/61 (32.8)  24/137 (17.5)  0.017  Procedural result, n/N (%)           Device successb  198/198 (100)  61/61 (100)  137/137 (100)  n.a.   Device failurec            Mortality  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Second valve used  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Conversion to surgery  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Device malfunction  1/198 (0.5)  0/61 (0)  1/137 (0.7)  0.504   Other events, n/N (%)            Complete AV block with PPI  3/198 (1.5)  1/61 (1.6)  2/137 (1.5)  1.000    Aortic root rupture  0/198 (0)  0/61 (0)  0/137 (0)  n.a.  a Defined as dissection, aortic root rupture or uncontrolled bleeding. b Defined according to VARC-2 as the absence of death, correct positioning of a single prosthetic heart valve and its intended performance. c Defined as the presence of any of the criteria outlined in VARC-2. AV: atrioventricular; BAV: balloon aortic valvuloplasty; n.a.: not applicable; PPI: permanent pacemaker implantation; TA: transapical; TAVI: transcatheter aortic valve implantation; THV: transcatheter heart valve; VARC-2: Valve Academic Research Consortium-2. Procedural outcomes Device success (defined as the absence of death, correct positioning of a single prosthetic heart valve and achievement of intended performance, as defined by VARC-2 [12]) was achieved in 100% of patients. Only one incidence of valve malfunction was documented (intraprocedural balloon rupture), which occurred in the group without BAV and was corrected without further complications. The median duration of the TAVI procedure and the amount of contrast agent used were statistically comparable between the with BAV and without BAV groups (85 vs 74.5 min; P = 0.295 and 85 vs 80 ml; t-test: P = 0.965, respectively), with a significant shorter median fluoroscopy time in the without group (4 vs 5 min; t-test: P = 0.039). In terms of procedural complications, only the proportion of patients requiring catecholamine treatment differed significantly, affecting 32.8% of patients in the group with BAV compared with only 17.5% of the group without BAV (χ2 test: P = 0.017). Access complications were documented for 1 patient undergoing TA-TAVI without BAV (0.7%), while 10 cases of haemodynamic instability were reported [4 in the with group (6.6%) and 6 in the without group (4.4%; χ2 test: P = 0.518)]. Post-procedural outcomes For both groups of patients, transvalvular pressure gradients were significantly lower post-TAVI compared with the respective prior values (Fig. 2). Peak gradients fell from a mean of 70.0 to 8.9 mmHg (−61.1 mmHg; t-test: P < 0.001) for the group with BAV and from a mean of 66.8 to 9.4 mmHg (−57.4 mmHg; t-test: P < 0.001) for the group without BAV. Mean gradients fell from 43.1 to 4.8 mmHg (−38.3 mmHg; t-test: P < 0.001) and 40.9 to 5.7 mmHg (−35.2 mmHg; t-test: P < 0.001), respectively. These represent changes of similar magnitudes in each case. No significant differences were found between the groups regarding the decrease in peak and mean pressure gradients (t-test: P = 0.585 and P = 0.285, respectively). Figure 2: View largeDownload slide AV mean and peak gradients prior to and directly after transapical transcatheter aortic valve implantation. (A) Peak pressure gradients across the AV (mmHg). (B) Mean pressure gradients across the AV (mmHg). AV: aortic valve; BAV: balloon aortic valvuloplasty. Figure 2: View largeDownload slide AV mean and peak gradients prior to and directly after transapical transcatheter aortic valve implantation. (A) Peak pressure gradients across the AV (mmHg). (B) Mean pressure gradients across the AV (mmHg). AV: aortic valve; BAV: balloon aortic valvuloplasty. Compared with the patients who underwent TA-TAVI with BAV, a higher proportion of those without BAV had no/trace PVL (84.7% vs 78.7%) and a lower proportion had mild PVL (14.6% vs 21.3%), though this was not statistically significant (χ2 test: P = 0.413; Fig. 3). Only 1 patient experienced moderate PVL (without BAV group) and no patients were reported to have severe PVL. Figure 3: View largeDownload slide Paravalvular leakage after transapical transcatheter aortic valve implantation with or without BAV. BAV: balloon aortic valvuloplasty. Figure 3: View largeDownload slide Paravalvular leakage after transapical transcatheter aortic valve implantation with or without BAV. BAV: balloon aortic valvuloplasty. Outcomes at 30 days and 6 months Compared to the values at baseline, the proportion of patients in NYHA Class III/IV at 30 days post-TAVI had fallen from 85.2% to just 1.7% in the group that underwent TA-TAVI with BAV and from 85.4% to just 2.3% in the group that underwent TA-TAVI without BAV, with no significant differences between groups. The composite primary evaluation criterion at 30 days (all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and PPI) occurred in 16 of 61 (26.2%) patients in the group with BAV and 26 of 137 (19.0%) patients in the group without BAV, but the difference was not found to be significant [adjusted OR 0.71, 95% confidence interval (CI) 0.34–1.47; Table 3]. Furthermore, the presence of BAV predilation did not affect the odds of reaching any of the individual components of the primary end-point. The odds of PPI were slightly increased in the BAV group (14.8% vs 10.2% for no BAV); however, this was not statistically significant. There was also no effect on the odds of life-threatening bleeding (3.3 with BAV vs 4.4% without BAV) or major vascular complications (3.3% with BAV vs 5.8% without BAV). Table 3: Outcomes at 30 days post-TA-TAVI   TAVI with BAV, n/N (%)  TAVI without BAV, n/N (%)  Unadjusted OR (95% CI)  Adjusteda OR (95% CI)  Primary evaluation criterionb  16/61 (26.2)  26/137 (19.0)  0.66 (0.32–1.34)  0.71 (0.34–1.47)   All-cause mortality  3/61 (4.9)  6/137 (4.4)  0.89 (0.21–3.66)  0.88 (0.25–3.15)   Non-fatal stroke  1/61 (1.6)  0/137 (0)  n.a.  0.76 (0.020–2.85)   Non-fatal MI  1/61 (1.6)  1/137 (0.7)  0.44 (0.03–7.17)  0.85 (0.23–3.11)   Renal failurec  6/61 (9.8)  11/137 (8.0)  0.80 (0.28–2.27)  0.85 (0.31–2.31)   Dialysis dependentc  3/61 (4.9)  7/137 (5.1)  1.04 (0.26–4.17)  0.97 (0.28–3.41)   Increased serum creatinined  3/61 (4.9)  4/137 (2.9)  0.58 (0.13–2.68)  0.87 (0.29–2.59)   PPI  9/61 (14.8)  14/137 (10.2)  0.66 (0.27–1.61)  0.68 (0.28–1.61)  Life-threatening bleeding  2/61 (3.3)  6/137 (4.4)  1.35 (0.27–6.89)  1.47 (0.35–6.23)  Major vascular complications  2/61 (3.3)  8/137 (5.8)  1.83 (0.38–8.88)  2.01 (0.52–8.42)  Valve- or HF-related hospitalization  1/61 (1.6)  0/137 (0)  n.a.  n.a.  Valve-related dysfunction  0/61 (0)  0/137 (0)  n.a.  n.a.  Angina CCS Class III or IV  0/58 (0)  0/124 (0)  n.a.  n.a.    TAVI with BAV, n/N (%)  TAVI without BAV, n/N (%)  Unadjusted OR (95% CI)  Adjusteda OR (95% CI)  Primary evaluation criterionb  16/61 (26.2)  26/137 (19.0)  0.66 (0.32–1.34)  0.71 (0.34–1.47)   All-cause mortality  3/61 (4.9)  6/137 (4.4)  0.89 (0.21–3.66)  0.88 (0.25–3.15)   Non-fatal stroke  1/61 (1.6)  0/137 (0)  n.a.  0.76 (0.020–2.85)   Non-fatal MI  1/61 (1.6)  1/137 (0.7)  0.44 (0.03–7.17)  0.85 (0.23–3.11)   Renal failurec  6/61 (9.8)  11/137 (8.0)  0.80 (0.28–2.27)  0.85 (0.31–2.31)   Dialysis dependentc  3/61 (4.9)  7/137 (5.1)  1.04 (0.26–4.17)  0.97 (0.28–3.41)   Increased serum creatinined  3/61 (4.9)  4/137 (2.9)  0.58 (0.13–2.68)  0.87 (0.29–2.59)   PPI  9/61 (14.8)  14/137 (10.2)  0.66 (0.27–1.61)  0.68 (0.28–1.61)  Life-threatening bleeding  2/61 (3.3)  6/137 (4.4)  1.35 (0.27–6.89)  1.47 (0.35–6.23)  Major vascular complications  2/61 (3.3)  8/137 (5.8)  1.83 (0.38–8.88)  2.01 (0.52–8.42)  Valve- or HF-related hospitalization  1/61 (1.6)  0/137 (0)  n.a.  n.a.  Valve-related dysfunction  0/61 (0)  0/137 (0)  n.a.  n.a.  Angina CCS Class III or IV  0/58 (0)  0/124 (0)  n.a.  n.a.  a Adjusted for baseline characteristics (Tables 1 and 2) such as age, gender, previous MI, stroke/TIA, prior pacemaker, creatinine ≥2.0 mg/dl, LVEF, NYHA Class III/IV. b Defined as a composite of all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and pacemaker implantation (as defined by VARC-2) within 30 days after TAVI [12]. c Excluding patients with dialysis prior to TAVI. d Acute kidney injury according to AKIN criteria Stage 2 or 3. BAV: balloon aortic valvuloplasty; CCS: Canadian Cardiovascular Society; CI: confidence interval; HF: heart failure; LVEF: left ventricular ejection fraction; MI: myocardial infarction; n.a.: not applicable; NYHA: New York Heart Association; OR: odds ratio; PPI: permanent pacemaker implantation; TA: transapical; TAVI: transcatheter aortic valve implantation; TIA: transient ischaemic attack; VARC-2: Valve Academic Research Consortium-2. The same composite evaluation criterion (as the primary) judged at 6 months occurred in 19 of 61 (31.1%) patients in the group with BAV and 34 of 137 (24.8%) patients in the group without BAV, with no differences between groups (OR 0.74, 95% CI 0.37–1.47; Table 4). Furthermore, there were no statistically significant differences in other outcomes, although the ORs indicated a reduction in cardiovascular death and non-fatal stroke but with a wide CI. Table 4: Outcomes at 6-month post-TA-TAVI   TAVI with BAV, n/N (%)  TAVI without BAV, n/N (%)  Unadjusted OR (95% CI)  Adjusteda OR (95% CI)  Combined end-pointb  19/61 (31.1)  34/137 (24.8)  0.73 (0.38–1.42)  0.74 (0.37–1.47)  All-cause mortality  6/61 (9.8)  13/137 (9.5)  0.96 (0.35–2.66)  0.85 (0.32–2.27)  Cardiovascular death  2/61 (3.3)  2/137 (1.5)  0.44 (0.06–3.18)  0.50 (0.12–2.18)  Non-fatal stroke  2/61 (3.3)  2/137 (1.5)  0.44 (0.06–3.18)  0.45 (0.10–2.08)  Non-fatal MI  1/61 (1.6)  1/137 (0.7)  0.44 (0.03–7.17)  0.85 (0.23–3.11)  New permanent pacemaker  9/61 (14.8)  16/137 (11.7)  0.76 (0.32–1.84)  0.77 (0.33–1.80)  Valve thrombosis  0/61 (0)  0/137 (0)  n.a.  n.a.  Endocarditis  0/61 (0)  0/137 (0)  n.a.  n.a.  Valve- or HF-related hospitalization  1/61 (1.6)  4/137 (2.9)  1.81 (0.20–16.49)  1.34 (0.27–6.67)    TAVI with BAV, n/N (%)  TAVI without BAV, n/N (%)  Unadjusted OR (95% CI)  Adjusteda OR (95% CI)  Combined end-pointb  19/61 (31.1)  34/137 (24.8)  0.73 (0.38–1.42)  0.74 (0.37–1.47)  All-cause mortality  6/61 (9.8)  13/137 (9.5)  0.96 (0.35–2.66)  0.85 (0.32–2.27)  Cardiovascular death  2/61 (3.3)  2/137 (1.5)  0.44 (0.06–3.18)  0.50 (0.12–2.18)  Non-fatal stroke  2/61 (3.3)  2/137 (1.5)  0.44 (0.06–3.18)  0.45 (0.10–2.08)  Non-fatal MI  1/61 (1.6)  1/137 (0.7)  0.44 (0.03–7.17)  0.85 (0.23–3.11)  New permanent pacemaker  9/61 (14.8)  16/137 (11.7)  0.76 (0.32–1.84)  0.77 (0.33–1.80)  Valve thrombosis  0/61 (0)  0/137 (0)  n.a.  n.a.  Endocarditis  0/61 (0)  0/137 (0)  n.a.  n.a.  Valve- or HF-related hospitalization  1/61 (1.6)  4/137 (2.9)  1.81 (0.20–16.49)  1.34 (0.27–6.67)  a Adjusted for baseline characteristics (Tables 1 and 2) age, gender, previous MI, stroke/TIA, prior pacemaker, creatinine ≥2.0 mg/dl, LVEF, NYHA Class III/IV. b Defined as a composite of all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and pacemaker implantation. BAV: balloon aortic valvuloplasty; CI: confidence interval; HF: heart failure; LVEF: left ventricular ejection fraction; MI: myocardial infarction; n.a.: not applicable; NYHA: New York Heart Association; OR: odds ratio; TA: transapical; TAVI: transcatheter aortic valve implantation; TIA: transient ischaemic attack. DISCUSSION The EASE-IT TA registry has demonstrated high success rates, clinical efficacy and safety of performing TA-TAVI without BAV in a real-world setting. Compared to conventional TA-TAVI with BAV, our findings suggest that the approach without BAV is at least comparable, with several potential safety advantages, including considerable reductions in the need for procedural catecholamine use. Procedural data It is logical to assume that omitting a step in a surgical procedure would result in time-saving, and this has been shown by several TF-TAVI studies that report significantly shorter procedural times in the absence of BAV [4, 8, 9]. In addition, a pilot study in 20 TA-TAVI patients by Wendler et al. [5] also reported significantly reduced procedural times when the BAV step was omitted (mean time of 75 ± 5 min compared with 122 ± 21 min with BAV; P < 0.001). As such, similar time-saving was expected in this study. However, average procedural times in the absence of BAV were found to be only 4.9 min shorter, whereas a significant reduction in fluoroscopy was found (difference 3.2 min; P = 0.039). In comparison with TF-TAVI, where the valvuloplasty balloon has to travel between the groin and the aortic valve, the BAV step prior to TA-TAVI should be much shorter. It is therefore possible that this study was underpowered to detect such a small difference in procedure duration. Device success was found for all TA-TAVI patients in this study, with no mortality, aortic root rupture, requirement for a second valve or conversion to surgery. This is a further demonstration of the feasibility and safety of performing TA-TAVI without BAV. Periprocedural complications A decreased (if non-significant) odds of balloon post-dilation was required in patients undergoing TA-TAVI without BAV compared to those undergoing the procedure with BAV. Several TF-TAVI studies have published similar findings, with Conradi et al. [8] reporting 11.5% of patients who underwent TF-TAVI with BAV required post-dilation compared to 0% of those without BAV and Kim et al. [4] reporting respective values of 11.1% and 7.1%. This suggests that apposition of the THV to the native aortic annulus may be more efficient, where prior BAV has not been performed. However, in this study, although all patients were deemed to be suitable for BAV omission, the procedure was performed at the discretion of the treating physician. It is, therefore, possible that certain patients had native valve characteristics, such as a high degree of calcification, which influenced their decision. The lack of difference in need for post-dilation between the 2 groups may indicate that this treatment decision was appropriate. It is possible that for some of the patients who underwent BAV, post-dilation may have been necessary if the predilation had been omitted. Similarly, although some studies have previously demonstrated decreased odds of PVL in the absence of BAV [6, 8], the difference in favour of the group that underwent TAVI without BAV in this study was not significant. In combination, these studies suggest that there may be a potential safety advantage of omitting the BAV step in TA-TAVI; however, larger cohorts would need to be analysed to clarify this. The proportion of patients requiring catecholamine treatment for low cardiac output was significantly lower in the absence of BAV, at almost half that of the group with BAV. Commonly known reasons for intraprocedural circulatory depression requiring catecholamine administration are severe bradycardia, third-degree atrioventricular block, coronary ostia obstruction and severe aortic regurgitation [13]. These are all known to occur following BAV and/or THV deployment. Rapid pacing, which is required during the BAV step in TA-TAVI, is also associated with reduced cardiac output. It is therefore logical that omission of BAV would result in a reduction in the number of patients requiring the use of catecholamine. Considering that the use of agents such as dopamine in cardiac surgery has been associated with complications such as tachycardia, arrhythmias and myocardial, intestinal and renal ischaemia [14], this finding is clinically relevant. Removing the BAV step may, therefore, offer indirect safety advantages. Post-procedural efficacy Peak and mean pressure gradients were reduced to a similar extent in the 2 groups, demonstrating equivalent procedural success. Because of the non-randomized design of the study, we cannot say how many of the patients who had BAV would have displayed poorer gradient reductions if this step had been omitted from the TAVI procedure. However, as other studies have reported similar findings, it seems that BAV is often not necessary for ensuring the correct function of the implanted valve [8–10]. Safety at 30 days and 6 months At 30 days and 6 months, there was no significant difference in the occurrence of the primary end-point (all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and PPI). Furthermore, when considering the components individually, the 2 groups displayed similar odds of each type of event. After multivariate adjustment, the use of BAV predilation did not affect the likelihood of any of the end-points. This demonstrated that the short-term safety of the 2 approaches was at least comparable for most patients. Again, it is likely that a proportion of the patients who received BAV may have had a poorer outcome in the absence of this step of the TAVI procedure. There was a numerically, but not statistically, higher incidence of a requirement for PPI in the group of patients who underwent BAV compared to those who did not. This follows the trend observed in the studies by Grube et al. [7] (27.8% vs 11.7%), Fiorina et al. [6] (15.5% vs 5.5%) and Islas et al. [9] (14.1 vs 6.3%) in patients undergoing TF-TAVI; the majority of the studies found the difference to be statistically significant. Furthermore, Gensas et al. [15] previously identified BAV as an independent predictor of PPI requirement in TAVI patients (OR 1.75, 95% CI 1.02–3.02; P = 0.04). Thus, evidence points towards an imbalance of patient numbers within the study groups, resulting in suboptimal statistical power being responsible for a lack of significance detection. Limitations One factor that was unfortunately not recorded was the degree of native valve calcification. As this would likely contribute to the decision of whether to perform BAV, this was a significant limitation. However, patients were only included in the registry if they were deemed to be suitable for TA-TAVI both with and without BAV; therefore, the level of calcification should not have varied significantly between the groups. Observational data typically contained gaps and errors. However, the prospective design and inclusion of site monitoring allowed us to substantially minimize this limitation. CONCLUSIONS This study that there is little justification for maintaining the BAV step in many TA-TAVI procedures. Identification of patient characteristics that indicate a necessity for BAV predilation should allow this step to be safely omitted in the majority of TA-TAVI cases. ACKNOWLEDGEMENTS Data were captured using the s4trials software provided by Software for Trials Europe GmbH, Berlin, Germany. Helen Sims (Institute for Pharmacology and Preventive Medicine) provided editorial support during the preparation of this article. Funding This work was supported by the Edwards Lifesciences, Nyon, Switzerland. Conflict of interest: Justus Strauch, Daniel Wendt, Anno Diegeler, Martin Heimeshoff, Steffen Hofmann, David Holzhey, Frank Oertel, Thorsten Wahlers and Holger Schröfel report to have received research funding and/or speaker honoraria and/or to have proctored for Edwards Lifesciences. Peter Bramlage and Cornelia Deutsch are representatives of the sponsor IPPMed, Cloppenburg, Germany, which received a research grant from Edwards. Martin Thoenes and Jana Kurucova report to be employed by Edwards. REFERENCES 1 Walther T, Dewey T, Borger MA, Kempfert J, Linke A, Becht R et al.   Transapical aortic valve implantation: step by step. Ann Thorac Surg  2009; 87: 276– 83. Google Scholar CrossRef Search ADS PubMed  2 Ben-Dor I, Pichard AD, Satler LF, Goldstein SA, Syed AI, Gaglia MA et al.   Complications and outcome of balloon aortic valvuloplasty in high-risk or inoperable patients. JACC Cardiovasc Interv  2010; 3: 1150– 6. Google Scholar CrossRef Search ADS PubMed  3 Mendiz OA, Fraguas H, Lev GA, Valdivieso LR, Favaloro RR. Transcatheter aortic valve implantation without balloon predilation: a single-center pilot experience. Catheter Cardiovasc Intervent  2013; 82: 292– 7. Google Scholar CrossRef Search ADS   4 Kim WK, Praz F, Blumenstein J, Liebetrau C, Gaede L, Van Linden A et al.   Transfemoral aortic valve implantation of Edwards SAPIEN 3 without predilatation. Catheter Cardiovasc Interv  2017; 89: E38– 43. Google Scholar CrossRef Search ADS PubMed  5 Wendler O, Dworakowski R, Monaghan M, MacCarthy PA. Direct transapical aortic valve implantation: a modified transcatheter approach avoiding balloon predilatation. Eur J Cardiothorac Surg  2012; 42: 734– 6. Google Scholar CrossRef Search ADS PubMed  6 Fiorina C, Maffeo D, Curello S, Lipartiti F, Chizzola G, D’Aloia A et al.   Direct transcatheter aortic valve implantation with self-expandable bioprosthesis: feasibility and safety. Cardiovasc Revasc Med  2014; 15: 200– 3. Google Scholar CrossRef Search ADS PubMed  7 Grube E, Naber C, Abizaid A, Sousa E, Mendiz O, Lemos P et al.   Feasibility of transcatheter aortic valve implantation without balloon pre-dilation: a pilot study. JACC Cardiovasc Interv  2011; 4: 751– 7. Google Scholar CrossRef Search ADS PubMed  8 Conradi L, Schaefer A, Seiffert M, Schirmer J, Schaefer U, Schön G et al.   Transfemoral TAVI without pre-dilatation using balloon-expandable devices: a case-matched analysis. Clin Res Cardiol  2015; 104: 735– 42. Google Scholar CrossRef Search ADS PubMed  9 Islas F, Almería C, García-Fernández E, Jiménez P, Nombela-Franco L, Olmos C et al.   Usefulness of echocardiographic criteria for transcatheter aortic valve implantation without balloon predilation: a single-center experience. J Am Soc Echocardiogr  2015; 28: 423– 9. Google Scholar CrossRef Search ADS PubMed  10 Möllmann H, Kim W-K, Kempfert J, Blumenstein J, Liebetrau C, Nef H et al.   Transfemoral aortic valve implantation of Edwards SAPIEN XT without predilatation is feasible. Clin Cardiol  2014; 37: 667– 71. Google Scholar CrossRef Search ADS PubMed  11 Bramlage P, Strauch J, Schrofel H. Balloon expandable transcatheter aortic valve implantation with or without pre-dilation of the aortic valve: rationale and design of a multicenter registry (EASE-IT). BMC Cardiovasc Disord  2014; 14: 160. Google Scholar CrossRef Search ADS PubMed  12 Kappetein AP, Head SJ, Genereux P, Piazza N, van Mieghem NM, Blackstone EH et al.   Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2). Eur J Cardiothorac Surg  2012; 42: S45– 60. Google Scholar CrossRef Search ADS PubMed  13 Laborde J-C, Brecker SJD, Roy D, Jahangiri M. Complications at the time of transcatheter aortic valve implantation. Methodist DeBakey Cardiovasc J  2012; 8: 38– 41. Google Scholar CrossRef Search ADS PubMed  14 Alsabbagh MM, Asmar A, Ejaz NI, Aiyer RK, Kambhampati G, Ejaz AA. Update on clinical trials for the prevention of acute kidney injury in patients undergoing cardiac surgery. Am J Surg  2013; 206: 86– 95. Google Scholar CrossRef Search ADS PubMed  15 Gensas CS, Caixeta A, Siqueira D, Carvalho LA, Sarmento-Leite R, Mangione JA et al.   Predictors of permanent pacemaker requirement after transcatheter aortic valve implantation: insights from a Brazilian registry. Int J Cardiol  2014; 175: 248– 52. Google Scholar CrossRef Search ADS PubMed  © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

Balloon-expandable transapical transcatheter aortic valve implantation with or without predilation of the aortic valve: results of a multicentre registry

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Oxford University Press
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1010-7940
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1873-734X
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10.1093/ejcts/ezx397
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Abstract

Abstract OBJECTIVES To assess safety and efficacy of transapical transcatheter aortic valve implantation (TA-TAVI) in the absence of predilation using balloon aortic valvuloplasty (BAV). Predilation of the stenosed valve using BAV is a routine step in TA-TAVI; however, evidence supporting its clinical value is lacking, and several studies have linked it with higher complication rates. METHODS A prospective, two-armed, multicentre registry (EASE-IT TA) to gather data on patients undergoing TA-TAVI with or without BAV, using the Edwards SAPIEN 3 valve was designed. The primary evaluation criterion was a composite of all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, acute kidney injury and pacemaker implantation [per Valve Academic Research Consortium-2 (VARC-2)] within 30 days after TAVI. RESULTS A total of 198 subjects underwent TA-TAVI, 61 with and 137 without BAV. Patient characteristics were comparable at baseline (mean ± SD: age 80.3 ± 5.7 years; logistic EuroSCORE 20.2 ± 12.6). Similar reductions in peak and mean transvalvular gradients were observed post-procedurally. There was a significant reduction of fluoroscopy time without BAV (4.7 vs 7.9 min; P = 0.039) and significantly decreased odds of catecholamine administration (17.5% vs 32.8%; P = 0.017). A decreased odds of the primary evaluation criterion in patients without BAV after 30 days (adjusted odds ratio 0.71; 95% confidence interval 0.34–1.82) and the same composite end-point after 6 months (adjusted odds ratio 0.74; 95% confidence interval 0.37–1.47) were not significant even after multivariable adjustment. CONCLUSIONS TA-TAVI without BAV appears to be at least equal to its conventional counterpart in terms of efficacy and may offer advantages in terms of safety. Thus, there appears to be little justification for maintaining the BAV step in TA-TAVI for many patients. EASE-IT, Transapical, Transcatheter aortic valve implantation, Balloon aortic valvuloplasty INTRODUCTION Dilation of the aortic valve using an expandable balloon [balloon aortic valvuloplasty (BAV)] has previously been considered an obligatory step for preparing the landing zone prior to deployment of the transcatheter heart valve (THV) in transcatheter aortic valve implantation (TAVI). This step provides an opportunity to assess the dimensions of the native valve, evaluate the risk for coronary occlusion and examine the potential for ‘balloon jump’ [1]. However, BAV is also associated with several serious complications, including haemodynamic failure, arrhythmia, atrioventricular block, systemic embolism, myocardial infarction (MI) and bleeding following cardiac perforation or trauma-mediated aortic root rupture [2]. Considering that these complications are potentially life-threatening, omission of BAV from the TAVI procedure has become increasingly popular among physicians [3–5]. The clinical value of TAVI without BAV has principally been investigated in the context of transfemoral (TF)-TAVI. Results from these studies have been encouraging, with reported technical success rates ranging from 85% to 96.7% [3, 4, 6–8] and procedural-related mortality rates between 2.5% and 7.7% [3, 4, 7–9]. Indeed, recent publications have reported the superiority of TF-TAVI without BAV over with BAV in terms of incidence of paravalvular leakage (PVL) [6, 8], procedural times [8, 9], fluoroscopy times [8], contrast agent volumes [6, 8, 10], rates of permanent pacemaker implantation (PPI) and 30-day mortality [9]. However, to our knowledge, only 1 article has been published regarding transapical (TA)-TAVI with an Edwards SAPIEN valve without BAV and was a pilot study involving just 6 patients [5]. The authors reported successful deployment in 100% of patients, accompanied by shorter procedural durations, decreased radiation exposure and reduced contrast agent volumes. They also proposed that TA-TAVI without BAV may reduce the probability of haemodynamic instability in patients with a diminished left ventricular ejection fraction. Clearly, larger comparative studies are required to further clarify the potential risks and benefits associated with eliminating the BAV step from the TA-TAVI procedure. Consequently, we designed a prospective, two-armed, multicentre registry (EASE-IT TA) to gather real-world data on patients undergoing TA-TAVI using the Edwards SAPIEN 3 THV, either with or without BAV. The data gathered on procedural aspects, efficacy and safety outcomes for each group of patients were compared, with the aim of clarifying the clinical value of the BAV step and the safety advantages, if any, of omitting it. MATERIALS AND METHODS The EASE-IT TA is a multicentre, prospective, two-armed, observational registry, established between April 2014 and February 2016. Prior ethical approval was obtained from the relevant ethics committees at each site. Only patients providing written informed consent were included. Design and study participants The design and rationale for the EASE-IT TA has previously been described [11]. Briefly, subjects were recruited from 10 German sites with appropriate training in the use of the Edwards SAPIEN 3 and the Ascendra Balloon Catheter (Edwards Lifesciences, Irvine, CA, USA) and prior experience of at least 20 TA-TAVI implantations. Patients aged 18 years or older with an indication for TAVI according to the Edwards SAPIEN 3 instructions (both with and without BAV) were eligible for study inclusion. Patients with a logistic EuroSCORE >50%, mitral or tricuspid valvular insufficiency >Grade II, previous aortic valve replacement, uncontrolled atrial fibrillation, left ventricular or atrial thrombus, recent cerebrovascular event, a high probability of non-adherence to follow-up or for whom the use of the Edwards SAPIEN 3 or the Ascendra Balloon Catheter was contraindicated based on instructions for use were excluded. At each site, the decision for a patient to receive TA-TAVI with or without BAV was made by their treating physician prior to enrolment in the study and was independent from the registry. TA access was selected according to patient characteristics, as well as physician preference, and the standard practice at each site. BAV was performed at the discretion of the treating physician. TA-TAVI with BAV was performed as described by Walther et al. [1], while that without BAV was carried out in a similar manner to that suggested by Wendler et al. [5]. Following study completion, 20% of participating sites underwent source data verification to ensure data validity. Study objectives The primary objective was to determine clinical safety as a composite evaluation of events (all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and PPI), which occurred up to 30 days after TA-TAVI. These events were defined per the Valve Academic Research Consortium-2 (VARC-2) consensus document [12]. Secondary objectives were to determine the rates of each of these events considered individually, periprocedural data (procedural duration, duration of radiation exposure, volume of contrast agent used and aortic root rupture), PVL, change in peak and mean transvalvular gradients post-TAVI and change in New York Heart Association (NYHA) class at 30-day follow-up relative to baseline. Statistical analysis The sample size for EASE-IT was established based on the previously reported event rates and the feasibility to detect an absolute risk reduction for the primary evaluation criterion of 13% at 30 days while taking into consideration a 10% dropout rate [11]. Under these assumptions, the power of the registry was 80%. However, based on the real-world nature of such registries, there was an unequal recruitment into the patient groups, resulting in 61 patients with and 137 patients without BAV. Data for the groups that underwent TA-TAVI with BAV were compared to those without BAV on an intention-to-treat basis using descriptive data analysis. Categorical variables were presented as frequency distributions, while continuous variables were reported as median (range) or mean ± standard deviation, as appropriate. Groups were tested for equal distribution in baseline variables by χ2 test for dichotomuous variables and by the t-test for continuous variables. The odds ratio (OR) for events occurring by 30-day follow-up in the 2 groups was calculated using a logistic model, which included age, gender, left ventricular ejection fraction, previous MI, stroke/transient ischaemic attack, prior PPI, creatinine ≥2.0 mg/dl, and NYHA Class III/IV as covariables using the Firth penalized maximum likelihood estimation to reduce bias in the parameter estimates because of the low number of events in some end-points. Unadjusted ORs were calculated from frequency tables. Data were analysed using Statistical Analysis System (SAS) version 9.3 (SAS Institute Inc., Cary, NC, USA). RESULTS Of the 200 patients originally enrolled in the registry, 2 were excluded due to duplication (Fig. 1). Of the remaining 198 patients, 61 underwent TA-TAVI with BAV, while 137 underwent TA-TAVI without BAV. Figure 1: View largeDownload slide Patient flow. BAV: balloon aortic valvuloplasty; 30d: thirty days; FU: follow-up; 6 mo: 6 months. Figure 1: View largeDownload slide Patient flow. BAV: balloon aortic valvuloplasty; 30d: thirty days; FU: follow-up; 6 mo: 6 months. Patient characteristics When comparing the baseline characteristics of the with BAV group to the without BAV group, no significant differences were observed for any of the documented factors, which included age, female gender, body mass index, prevalence of comorbidities, history of cardiac events and aortic stenosis-related parameters (Table 1). Although not statistically different, a lower mean logistic EuroSCORE was seen for patients in the with BAV group compared to the without BAV group (17.6% vs 21.6%; P = 0.081). Table 1: Patient baseline characteristics and aortic stenosis-related parameters at baseline   Total (N = 198)  TAVI with BAV (N = 61)  TAVI without BAV (N = 137)  P-value  Age (years), mean ± SD  80.3 ± 5.7  80.5 ± 5.4  80.2 ± 5.9  0.762a  Female gender, n/N (%)  81/198 (40.9)  25/61 (41.0)  56/137 (40.9)  0.989  Body mass index (kg/m2), mean ± SD  27.0 ± 4.4  27.4 ± 5.0  26.9 ± 4.1  0.448a  Comorbidity, n/N (%)           Hypertension  186/198 (93.9)  59/61 (96.7)  127/137 (92.7)  0.274   Diabetes  75/198 (37.9)  27/61 (44.3)  48/137 (35.0)  0.217   Stroke/TIA  30/198 (15.2)  10/61 (16.4)  20/137 (14.6)  0.745   PAD  77/198 (38.9)  28/61 (45.9)  49/137 (35.8)  0.177   Pulmonary hypertension  23/197 (11.7)  7/61 (11.5)  16/136 (11.8)  0.953   Creatinine ≥2.0 mg/dl  10/198 (5.1)  3/61 (4.9)  7/137 (5.1)  1.000   Dialysis  3/198 (1.5)  2/61 (3.3)  1/137 (0.7)  0.175  Cardiac history, n/N (%)           CAD  128/198 (64.7)  36/61 (59.0)  92/137 (67.2)  0.269   Prior MI  21/198 (10.6)  6/61 (9.8)  15/137 (10.9)  0.814   Prior CV intervention  97/198 (49.0)  26/61 (42.6)  71/137 (51.8)  0.232   Prior pacemaker/ICD  28/198 (14.1)  8/61 (13.1)  20/137 (14.6)  0.782  Logistic EuroSCORE I (%), mean ± SD  20.2 ± 12.6  17.6 ± 10.2  21.6 ± 13.6  0.081a  Echocardiography of the aortic valve, mean ± SD           Peak gradient (mmHg)  67.9 ± 22.2  70.0 ± 21.4  66.8 ± 22.6  0.386a   Mean gradient (mmHg)  41.6 ± 13.6  43.1 ± 14.9  40.9 ± 12.9  0.317a   Vmax (m/s)  4.0 ± 1.2  4.0 ± 1.2  4.0 ± 1.2  0.958a  LVEF (%), mean ± SD  52.2 ± 12.8  54.1 ± 11.3  51.3 ± 13.4  0.159a  NYHA Class III/IV, n/N (%)  169/198 (85.4)  52/61 (85.2)  117/137 (85.4)  0.977  CCS Class III/IV, n/N (%)  42/197 (21.3)  14/61 (23.0)  28/136 (20.6)  0.708  Syncope, n/N (%)  20/198 (10.1)  4/61 (6.6)  16/137 (11.7)  0.270  Dizziness with exertion, n/N (%)  25/198 (12.6)  8/61 (13.1)  17/137 (12.4)  0.890    Total (N = 198)  TAVI with BAV (N = 61)  TAVI without BAV (N = 137)  P-value  Age (years), mean ± SD  80.3 ± 5.7  80.5 ± 5.4  80.2 ± 5.9  0.762a  Female gender, n/N (%)  81/198 (40.9)  25/61 (41.0)  56/137 (40.9)  0.989  Body mass index (kg/m2), mean ± SD  27.0 ± 4.4  27.4 ± 5.0  26.9 ± 4.1  0.448a  Comorbidity, n/N (%)           Hypertension  186/198 (93.9)  59/61 (96.7)  127/137 (92.7)  0.274   Diabetes  75/198 (37.9)  27/61 (44.3)  48/137 (35.0)  0.217   Stroke/TIA  30/198 (15.2)  10/61 (16.4)  20/137 (14.6)  0.745   PAD  77/198 (38.9)  28/61 (45.9)  49/137 (35.8)  0.177   Pulmonary hypertension  23/197 (11.7)  7/61 (11.5)  16/136 (11.8)  0.953   Creatinine ≥2.0 mg/dl  10/198 (5.1)  3/61 (4.9)  7/137 (5.1)  1.000   Dialysis  3/198 (1.5)  2/61 (3.3)  1/137 (0.7)  0.175  Cardiac history, n/N (%)           CAD  128/198 (64.7)  36/61 (59.0)  92/137 (67.2)  0.269   Prior MI  21/198 (10.6)  6/61 (9.8)  15/137 (10.9)  0.814   Prior CV intervention  97/198 (49.0)  26/61 (42.6)  71/137 (51.8)  0.232   Prior pacemaker/ICD  28/198 (14.1)  8/61 (13.1)  20/137 (14.6)  0.782  Logistic EuroSCORE I (%), mean ± SD  20.2 ± 12.6  17.6 ± 10.2  21.6 ± 13.6  0.081a  Echocardiography of the aortic valve, mean ± SD           Peak gradient (mmHg)  67.9 ± 22.2  70.0 ± 21.4  66.8 ± 22.6  0.386a   Mean gradient (mmHg)  41.6 ± 13.6  43.1 ± 14.9  40.9 ± 12.9  0.317a   Vmax (m/s)  4.0 ± 1.2  4.0 ± 1.2  4.0 ± 1.2  0.958a  LVEF (%), mean ± SD  52.2 ± 12.8  54.1 ± 11.3  51.3 ± 13.4  0.159a  NYHA Class III/IV, n/N (%)  169/198 (85.4)  52/61 (85.2)  117/137 (85.4)  0.977  CCS Class III/IV, n/N (%)  42/197 (21.3)  14/61 (23.0)  28/136 (20.6)  0.708  Syncope, n/N (%)  20/198 (10.1)  4/61 (6.6)  16/137 (11.7)  0.270  Dizziness with exertion, n/N (%)  25/198 (12.6)  8/61 (13.1)  17/137 (12.4)  0.890  a t-test was used to calculate P-values; categorical variables were analysed using the χ2 test. BAV: balloon aortic valvuloplasty; CAD: coronary artery disease; CCS: Canadian Cardiovascular Society; CV: cardiovascular; ICD: implantable cardioverter defibrillator; LVEF: left ventricular ejection fraction; MI: myocardial infraction; NYHA: New York Heart Association; PAD: peripheral artery disease; SD: standard deviation; TAVI: transcatheter aortic valve implantation; TIA: transient ischaemic attack; Vmax: maximum velocity. Procedural details Of the patients who underwent TA-TAVI with BAV, the majority underwent the predilation using a 20-mm balloon (80.7%) (Table 2). The most common valve implanted was the 26 mm (49.2% and 40.9% of the with BAV and without BAV patients, respectively). The proportion of patients requiring balloon post-dilation was slightly higher in the group with BAV (14.8%) compared to without (9.5%) TA-TAVI groups, though no statistically significant difference was detected. Table 2: Procedural details and outcomes of TA-TAVI   Total (N = 198)  TAVI with BAV (N = 61)  TAVI without BAV (N = 137)  P-value  Size of balloon used for predilation, n/N (%)  61/198 (30.8)  61/61 (100.0)  n.a.  n.a.   20 mm  46/194 (23.7)  46/57 (80.7)  n.a.  n.a.   22/23 mm  5/194 (2.6)  5/57 (8.8)  n.a.  n.a.   25/26 mm  6/194 (3.1)  6/57 (10.5)  n.a.  n.a.  Size of implanted THV, n/N (%)        0.470   23 mm  60/198 (30.3)  18/61 (29.5)  42/137 (30.7)     26 mm  86/198 (43.4)  30/61 (49.2)  56/137 (40.9)     29 mm  52/198 (26.3)  13/61 (21.3)  39/137 (28.5)    Requirement for balloon post-dilation, n/N (%)  22/198 (11.1)  9/61 (14.8)  13/137 (9.5)  0.276  Procedural characteristics, median (1st–3rd quartile)           Procedural duration (min)  76 (58–98)  85 (63–104)  74.5 (58.0–96.5)  0.295   Fluoroscopy time (min)  4 (3–6)  5 (4–6)  4 (3–5)  0.039   Contrast agent volume (ml)  80 (60–100)  85 (60–108)  80 (60–100)  0.965  Procedural complications, n/N (%)           Access complicationsa  1/198 (0.5)  0/61 (0)  1/137 (0.7)  0.504   Hemodynamic instability  10/198 (5.1)  4/61 (6.6)  6/137 (4.4)  0.518   Catecholamine use  44/198 (22.2)  20/61 (32.8)  24/137 (17.5)  0.017  Procedural result, n/N (%)           Device successb  198/198 (100)  61/61 (100)  137/137 (100)  n.a.   Device failurec            Mortality  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Second valve used  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Conversion to surgery  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Device malfunction  1/198 (0.5)  0/61 (0)  1/137 (0.7)  0.504   Other events, n/N (%)            Complete AV block with PPI  3/198 (1.5)  1/61 (1.6)  2/137 (1.5)  1.000    Aortic root rupture  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Total (N = 198)  TAVI with BAV (N = 61)  TAVI without BAV (N = 137)  P-value  Size of balloon used for predilation, n/N (%)  61/198 (30.8)  61/61 (100.0)  n.a.  n.a.   20 mm  46/194 (23.7)  46/57 (80.7)  n.a.  n.a.   22/23 mm  5/194 (2.6)  5/57 (8.8)  n.a.  n.a.   25/26 mm  6/194 (3.1)  6/57 (10.5)  n.a.  n.a.  Size of implanted THV, n/N (%)        0.470   23 mm  60/198 (30.3)  18/61 (29.5)  42/137 (30.7)     26 mm  86/198 (43.4)  30/61 (49.2)  56/137 (40.9)     29 mm  52/198 (26.3)  13/61 (21.3)  39/137 (28.5)    Requirement for balloon post-dilation, n/N (%)  22/198 (11.1)  9/61 (14.8)  13/137 (9.5)  0.276  Procedural characteristics, median (1st–3rd quartile)           Procedural duration (min)  76 (58–98)  85 (63–104)  74.5 (58.0–96.5)  0.295   Fluoroscopy time (min)  4 (3–6)  5 (4–6)  4 (3–5)  0.039   Contrast agent volume (ml)  80 (60–100)  85 (60–108)  80 (60–100)  0.965  Procedural complications, n/N (%)           Access complicationsa  1/198 (0.5)  0/61 (0)  1/137 (0.7)  0.504   Hemodynamic instability  10/198 (5.1)  4/61 (6.6)  6/137 (4.4)  0.518   Catecholamine use  44/198 (22.2)  20/61 (32.8)  24/137 (17.5)  0.017  Procedural result, n/N (%)           Device successb  198/198 (100)  61/61 (100)  137/137 (100)  n.a.   Device failurec            Mortality  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Second valve used  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Conversion to surgery  0/198 (0)  0/61 (0)  0/137 (0)  n.a.    Device malfunction  1/198 (0.5)  0/61 (0)  1/137 (0.7)  0.504   Other events, n/N (%)            Complete AV block with PPI  3/198 (1.5)  1/61 (1.6)  2/137 (1.5)  1.000    Aortic root rupture  0/198 (0)  0/61 (0)  0/137 (0)  n.a.  a Defined as dissection, aortic root rupture or uncontrolled bleeding. b Defined according to VARC-2 as the absence of death, correct positioning of a single prosthetic heart valve and its intended performance. c Defined as the presence of any of the criteria outlined in VARC-2. AV: atrioventricular; BAV: balloon aortic valvuloplasty; n.a.: not applicable; PPI: permanent pacemaker implantation; TA: transapical; TAVI: transcatheter aortic valve implantation; THV: transcatheter heart valve; VARC-2: Valve Academic Research Consortium-2. Procedural outcomes Device success (defined as the absence of death, correct positioning of a single prosthetic heart valve and achievement of intended performance, as defined by VARC-2 [12]) was achieved in 100% of patients. Only one incidence of valve malfunction was documented (intraprocedural balloon rupture), which occurred in the group without BAV and was corrected without further complications. The median duration of the TAVI procedure and the amount of contrast agent used were statistically comparable between the with BAV and without BAV groups (85 vs 74.5 min; P = 0.295 and 85 vs 80 ml; t-test: P = 0.965, respectively), with a significant shorter median fluoroscopy time in the without group (4 vs 5 min; t-test: P = 0.039). In terms of procedural complications, only the proportion of patients requiring catecholamine treatment differed significantly, affecting 32.8% of patients in the group with BAV compared with only 17.5% of the group without BAV (χ2 test: P = 0.017). Access complications were documented for 1 patient undergoing TA-TAVI without BAV (0.7%), while 10 cases of haemodynamic instability were reported [4 in the with group (6.6%) and 6 in the without group (4.4%; χ2 test: P = 0.518)]. Post-procedural outcomes For both groups of patients, transvalvular pressure gradients were significantly lower post-TAVI compared with the respective prior values (Fig. 2). Peak gradients fell from a mean of 70.0 to 8.9 mmHg (−61.1 mmHg; t-test: P < 0.001) for the group with BAV and from a mean of 66.8 to 9.4 mmHg (−57.4 mmHg; t-test: P < 0.001) for the group without BAV. Mean gradients fell from 43.1 to 4.8 mmHg (−38.3 mmHg; t-test: P < 0.001) and 40.9 to 5.7 mmHg (−35.2 mmHg; t-test: P < 0.001), respectively. These represent changes of similar magnitudes in each case. No significant differences were found between the groups regarding the decrease in peak and mean pressure gradients (t-test: P = 0.585 and P = 0.285, respectively). Figure 2: View largeDownload slide AV mean and peak gradients prior to and directly after transapical transcatheter aortic valve implantation. (A) Peak pressure gradients across the AV (mmHg). (B) Mean pressure gradients across the AV (mmHg). AV: aortic valve; BAV: balloon aortic valvuloplasty. Figure 2: View largeDownload slide AV mean and peak gradients prior to and directly after transapical transcatheter aortic valve implantation. (A) Peak pressure gradients across the AV (mmHg). (B) Mean pressure gradients across the AV (mmHg). AV: aortic valve; BAV: balloon aortic valvuloplasty. Compared with the patients who underwent TA-TAVI with BAV, a higher proportion of those without BAV had no/trace PVL (84.7% vs 78.7%) and a lower proportion had mild PVL (14.6% vs 21.3%), though this was not statistically significant (χ2 test: P = 0.413; Fig. 3). Only 1 patient experienced moderate PVL (without BAV group) and no patients were reported to have severe PVL. Figure 3: View largeDownload slide Paravalvular leakage after transapical transcatheter aortic valve implantation with or without BAV. BAV: balloon aortic valvuloplasty. Figure 3: View largeDownload slide Paravalvular leakage after transapical transcatheter aortic valve implantation with or without BAV. BAV: balloon aortic valvuloplasty. Outcomes at 30 days and 6 months Compared to the values at baseline, the proportion of patients in NYHA Class III/IV at 30 days post-TAVI had fallen from 85.2% to just 1.7% in the group that underwent TA-TAVI with BAV and from 85.4% to just 2.3% in the group that underwent TA-TAVI without BAV, with no significant differences between groups. The composite primary evaluation criterion at 30 days (all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and PPI) occurred in 16 of 61 (26.2%) patients in the group with BAV and 26 of 137 (19.0%) patients in the group without BAV, but the difference was not found to be significant [adjusted OR 0.71, 95% confidence interval (CI) 0.34–1.47; Table 3]. Furthermore, the presence of BAV predilation did not affect the odds of reaching any of the individual components of the primary end-point. The odds of PPI were slightly increased in the BAV group (14.8% vs 10.2% for no BAV); however, this was not statistically significant. There was also no effect on the odds of life-threatening bleeding (3.3 with BAV vs 4.4% without BAV) or major vascular complications (3.3% with BAV vs 5.8% without BAV). Table 3: Outcomes at 30 days post-TA-TAVI   TAVI with BAV, n/N (%)  TAVI without BAV, n/N (%)  Unadjusted OR (95% CI)  Adjusteda OR (95% CI)  Primary evaluation criterionb  16/61 (26.2)  26/137 (19.0)  0.66 (0.32–1.34)  0.71 (0.34–1.47)   All-cause mortality  3/61 (4.9)  6/137 (4.4)  0.89 (0.21–3.66)  0.88 (0.25–3.15)   Non-fatal stroke  1/61 (1.6)  0/137 (0)  n.a.  0.76 (0.020–2.85)   Non-fatal MI  1/61 (1.6)  1/137 (0.7)  0.44 (0.03–7.17)  0.85 (0.23–3.11)   Renal failurec  6/61 (9.8)  11/137 (8.0)  0.80 (0.28–2.27)  0.85 (0.31–2.31)   Dialysis dependentc  3/61 (4.9)  7/137 (5.1)  1.04 (0.26–4.17)  0.97 (0.28–3.41)   Increased serum creatinined  3/61 (4.9)  4/137 (2.9)  0.58 (0.13–2.68)  0.87 (0.29–2.59)   PPI  9/61 (14.8)  14/137 (10.2)  0.66 (0.27–1.61)  0.68 (0.28–1.61)  Life-threatening bleeding  2/61 (3.3)  6/137 (4.4)  1.35 (0.27–6.89)  1.47 (0.35–6.23)  Major vascular complications  2/61 (3.3)  8/137 (5.8)  1.83 (0.38–8.88)  2.01 (0.52–8.42)  Valve- or HF-related hospitalization  1/61 (1.6)  0/137 (0)  n.a.  n.a.  Valve-related dysfunction  0/61 (0)  0/137 (0)  n.a.  n.a.  Angina CCS Class III or IV  0/58 (0)  0/124 (0)  n.a.  n.a.    TAVI with BAV, n/N (%)  TAVI without BAV, n/N (%)  Unadjusted OR (95% CI)  Adjusteda OR (95% CI)  Primary evaluation criterionb  16/61 (26.2)  26/137 (19.0)  0.66 (0.32–1.34)  0.71 (0.34–1.47)   All-cause mortality  3/61 (4.9)  6/137 (4.4)  0.89 (0.21–3.66)  0.88 (0.25–3.15)   Non-fatal stroke  1/61 (1.6)  0/137 (0)  n.a.  0.76 (0.020–2.85)   Non-fatal MI  1/61 (1.6)  1/137 (0.7)  0.44 (0.03–7.17)  0.85 (0.23–3.11)   Renal failurec  6/61 (9.8)  11/137 (8.0)  0.80 (0.28–2.27)  0.85 (0.31–2.31)   Dialysis dependentc  3/61 (4.9)  7/137 (5.1)  1.04 (0.26–4.17)  0.97 (0.28–3.41)   Increased serum creatinined  3/61 (4.9)  4/137 (2.9)  0.58 (0.13–2.68)  0.87 (0.29–2.59)   PPI  9/61 (14.8)  14/137 (10.2)  0.66 (0.27–1.61)  0.68 (0.28–1.61)  Life-threatening bleeding  2/61 (3.3)  6/137 (4.4)  1.35 (0.27–6.89)  1.47 (0.35–6.23)  Major vascular complications  2/61 (3.3)  8/137 (5.8)  1.83 (0.38–8.88)  2.01 (0.52–8.42)  Valve- or HF-related hospitalization  1/61 (1.6)  0/137 (0)  n.a.  n.a.  Valve-related dysfunction  0/61 (0)  0/137 (0)  n.a.  n.a.  Angina CCS Class III or IV  0/58 (0)  0/124 (0)  n.a.  n.a.  a Adjusted for baseline characteristics (Tables 1 and 2) such as age, gender, previous MI, stroke/TIA, prior pacemaker, creatinine ≥2.0 mg/dl, LVEF, NYHA Class III/IV. b Defined as a composite of all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and pacemaker implantation (as defined by VARC-2) within 30 days after TAVI [12]. c Excluding patients with dialysis prior to TAVI. d Acute kidney injury according to AKIN criteria Stage 2 or 3. BAV: balloon aortic valvuloplasty; CCS: Canadian Cardiovascular Society; CI: confidence interval; HF: heart failure; LVEF: left ventricular ejection fraction; MI: myocardial infarction; n.a.: not applicable; NYHA: New York Heart Association; OR: odds ratio; PPI: permanent pacemaker implantation; TA: transapical; TAVI: transcatheter aortic valve implantation; TIA: transient ischaemic attack; VARC-2: Valve Academic Research Consortium-2. The same composite evaluation criterion (as the primary) judged at 6 months occurred in 19 of 61 (31.1%) patients in the group with BAV and 34 of 137 (24.8%) patients in the group without BAV, with no differences between groups (OR 0.74, 95% CI 0.37–1.47; Table 4). Furthermore, there were no statistically significant differences in other outcomes, although the ORs indicated a reduction in cardiovascular death and non-fatal stroke but with a wide CI. Table 4: Outcomes at 6-month post-TA-TAVI   TAVI with BAV, n/N (%)  TAVI without BAV, n/N (%)  Unadjusted OR (95% CI)  Adjusteda OR (95% CI)  Combined end-pointb  19/61 (31.1)  34/137 (24.8)  0.73 (0.38–1.42)  0.74 (0.37–1.47)  All-cause mortality  6/61 (9.8)  13/137 (9.5)  0.96 (0.35–2.66)  0.85 (0.32–2.27)  Cardiovascular death  2/61 (3.3)  2/137 (1.5)  0.44 (0.06–3.18)  0.50 (0.12–2.18)  Non-fatal stroke  2/61 (3.3)  2/137 (1.5)  0.44 (0.06–3.18)  0.45 (0.10–2.08)  Non-fatal MI  1/61 (1.6)  1/137 (0.7)  0.44 (0.03–7.17)  0.85 (0.23–3.11)  New permanent pacemaker  9/61 (14.8)  16/137 (11.7)  0.76 (0.32–1.84)  0.77 (0.33–1.80)  Valve thrombosis  0/61 (0)  0/137 (0)  n.a.  n.a.  Endocarditis  0/61 (0)  0/137 (0)  n.a.  n.a.  Valve- or HF-related hospitalization  1/61 (1.6)  4/137 (2.9)  1.81 (0.20–16.49)  1.34 (0.27–6.67)    TAVI with BAV, n/N (%)  TAVI without BAV, n/N (%)  Unadjusted OR (95% CI)  Adjusteda OR (95% CI)  Combined end-pointb  19/61 (31.1)  34/137 (24.8)  0.73 (0.38–1.42)  0.74 (0.37–1.47)  All-cause mortality  6/61 (9.8)  13/137 (9.5)  0.96 (0.35–2.66)  0.85 (0.32–2.27)  Cardiovascular death  2/61 (3.3)  2/137 (1.5)  0.44 (0.06–3.18)  0.50 (0.12–2.18)  Non-fatal stroke  2/61 (3.3)  2/137 (1.5)  0.44 (0.06–3.18)  0.45 (0.10–2.08)  Non-fatal MI  1/61 (1.6)  1/137 (0.7)  0.44 (0.03–7.17)  0.85 (0.23–3.11)  New permanent pacemaker  9/61 (14.8)  16/137 (11.7)  0.76 (0.32–1.84)  0.77 (0.33–1.80)  Valve thrombosis  0/61 (0)  0/137 (0)  n.a.  n.a.  Endocarditis  0/61 (0)  0/137 (0)  n.a.  n.a.  Valve- or HF-related hospitalization  1/61 (1.6)  4/137 (2.9)  1.81 (0.20–16.49)  1.34 (0.27–6.67)  a Adjusted for baseline characteristics (Tables 1 and 2) age, gender, previous MI, stroke/TIA, prior pacemaker, creatinine ≥2.0 mg/dl, LVEF, NYHA Class III/IV. b Defined as a composite of all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and pacemaker implantation. BAV: balloon aortic valvuloplasty; CI: confidence interval; HF: heart failure; LVEF: left ventricular ejection fraction; MI: myocardial infarction; n.a.: not applicable; NYHA: New York Heart Association; OR: odds ratio; TA: transapical; TAVI: transcatheter aortic valve implantation; TIA: transient ischaemic attack. DISCUSSION The EASE-IT TA registry has demonstrated high success rates, clinical efficacy and safety of performing TA-TAVI without BAV in a real-world setting. Compared to conventional TA-TAVI with BAV, our findings suggest that the approach without BAV is at least comparable, with several potential safety advantages, including considerable reductions in the need for procedural catecholamine use. Procedural data It is logical to assume that omitting a step in a surgical procedure would result in time-saving, and this has been shown by several TF-TAVI studies that report significantly shorter procedural times in the absence of BAV [4, 8, 9]. In addition, a pilot study in 20 TA-TAVI patients by Wendler et al. [5] also reported significantly reduced procedural times when the BAV step was omitted (mean time of 75 ± 5 min compared with 122 ± 21 min with BAV; P < 0.001). As such, similar time-saving was expected in this study. However, average procedural times in the absence of BAV were found to be only 4.9 min shorter, whereas a significant reduction in fluoroscopy was found (difference 3.2 min; P = 0.039). In comparison with TF-TAVI, where the valvuloplasty balloon has to travel between the groin and the aortic valve, the BAV step prior to TA-TAVI should be much shorter. It is therefore possible that this study was underpowered to detect such a small difference in procedure duration. Device success was found for all TA-TAVI patients in this study, with no mortality, aortic root rupture, requirement for a second valve or conversion to surgery. This is a further demonstration of the feasibility and safety of performing TA-TAVI without BAV. Periprocedural complications A decreased (if non-significant) odds of balloon post-dilation was required in patients undergoing TA-TAVI without BAV compared to those undergoing the procedure with BAV. Several TF-TAVI studies have published similar findings, with Conradi et al. [8] reporting 11.5% of patients who underwent TF-TAVI with BAV required post-dilation compared to 0% of those without BAV and Kim et al. [4] reporting respective values of 11.1% and 7.1%. This suggests that apposition of the THV to the native aortic annulus may be more efficient, where prior BAV has not been performed. However, in this study, although all patients were deemed to be suitable for BAV omission, the procedure was performed at the discretion of the treating physician. It is, therefore, possible that certain patients had native valve characteristics, such as a high degree of calcification, which influenced their decision. The lack of difference in need for post-dilation between the 2 groups may indicate that this treatment decision was appropriate. It is possible that for some of the patients who underwent BAV, post-dilation may have been necessary if the predilation had been omitted. Similarly, although some studies have previously demonstrated decreased odds of PVL in the absence of BAV [6, 8], the difference in favour of the group that underwent TAVI without BAV in this study was not significant. In combination, these studies suggest that there may be a potential safety advantage of omitting the BAV step in TA-TAVI; however, larger cohorts would need to be analysed to clarify this. The proportion of patients requiring catecholamine treatment for low cardiac output was significantly lower in the absence of BAV, at almost half that of the group with BAV. Commonly known reasons for intraprocedural circulatory depression requiring catecholamine administration are severe bradycardia, third-degree atrioventricular block, coronary ostia obstruction and severe aortic regurgitation [13]. These are all known to occur following BAV and/or THV deployment. Rapid pacing, which is required during the BAV step in TA-TAVI, is also associated with reduced cardiac output. It is therefore logical that omission of BAV would result in a reduction in the number of patients requiring the use of catecholamine. Considering that the use of agents such as dopamine in cardiac surgery has been associated with complications such as tachycardia, arrhythmias and myocardial, intestinal and renal ischaemia [14], this finding is clinically relevant. Removing the BAV step may, therefore, offer indirect safety advantages. Post-procedural efficacy Peak and mean pressure gradients were reduced to a similar extent in the 2 groups, demonstrating equivalent procedural success. Because of the non-randomized design of the study, we cannot say how many of the patients who had BAV would have displayed poorer gradient reductions if this step had been omitted from the TAVI procedure. However, as other studies have reported similar findings, it seems that BAV is often not necessary for ensuring the correct function of the implanted valve [8–10]. Safety at 30 days and 6 months At 30 days and 6 months, there was no significant difference in the occurrence of the primary end-point (all-cause mortality, non-fatal stroke, non-fatal MI, acute kidney injury and PPI). Furthermore, when considering the components individually, the 2 groups displayed similar odds of each type of event. After multivariate adjustment, the use of BAV predilation did not affect the likelihood of any of the end-points. This demonstrated that the short-term safety of the 2 approaches was at least comparable for most patients. Again, it is likely that a proportion of the patients who received BAV may have had a poorer outcome in the absence of this step of the TAVI procedure. There was a numerically, but not statistically, higher incidence of a requirement for PPI in the group of patients who underwent BAV compared to those who did not. This follows the trend observed in the studies by Grube et al. [7] (27.8% vs 11.7%), Fiorina et al. [6] (15.5% vs 5.5%) and Islas et al. [9] (14.1 vs 6.3%) in patients undergoing TF-TAVI; the majority of the studies found the difference to be statistically significant. Furthermore, Gensas et al. [15] previously identified BAV as an independent predictor of PPI requirement in TAVI patients (OR 1.75, 95% CI 1.02–3.02; P = 0.04). Thus, evidence points towards an imbalance of patient numbers within the study groups, resulting in suboptimal statistical power being responsible for a lack of significance detection. Limitations One factor that was unfortunately not recorded was the degree of native valve calcification. As this would likely contribute to the decision of whether to perform BAV, this was a significant limitation. However, patients were only included in the registry if they were deemed to be suitable for TA-TAVI both with and without BAV; therefore, the level of calcification should not have varied significantly between the groups. Observational data typically contained gaps and errors. However, the prospective design and inclusion of site monitoring allowed us to substantially minimize this limitation. CONCLUSIONS This study that there is little justification for maintaining the BAV step in many TA-TAVI procedures. Identification of patient characteristics that indicate a necessity for BAV predilation should allow this step to be safely omitted in the majority of TA-TAVI cases. ACKNOWLEDGEMENTS Data were captured using the s4trials software provided by Software for Trials Europe GmbH, Berlin, Germany. Helen Sims (Institute for Pharmacology and Preventive Medicine) provided editorial support during the preparation of this article. Funding This work was supported by the Edwards Lifesciences, Nyon, Switzerland. Conflict of interest: Justus Strauch, Daniel Wendt, Anno Diegeler, Martin Heimeshoff, Steffen Hofmann, David Holzhey, Frank Oertel, Thorsten Wahlers and Holger Schröfel report to have received research funding and/or speaker honoraria and/or to have proctored for Edwards Lifesciences. Peter Bramlage and Cornelia Deutsch are representatives of the sponsor IPPMed, Cloppenburg, Germany, which received a research grant from Edwards. Martin Thoenes and Jana Kurucova report to be employed by Edwards. REFERENCES 1 Walther T, Dewey T, Borger MA, Kempfert J, Linke A, Becht R et al.   Transapical aortic valve implantation: step by step. Ann Thorac Surg  2009; 87: 276– 83. Google Scholar CrossRef Search ADS PubMed  2 Ben-Dor I, Pichard AD, Satler LF, Goldstein SA, Syed AI, Gaglia MA et al.   Complications and outcome of balloon aortic valvuloplasty in high-risk or inoperable patients. JACC Cardiovasc Interv  2010; 3: 1150– 6. Google Scholar CrossRef Search ADS PubMed  3 Mendiz OA, Fraguas H, Lev GA, Valdivieso LR, Favaloro RR. Transcatheter aortic valve implantation without balloon predilation: a single-center pilot experience. Catheter Cardiovasc Intervent  2013; 82: 292– 7. Google Scholar CrossRef Search ADS   4 Kim WK, Praz F, Blumenstein J, Liebetrau C, Gaede L, Van Linden A et al.   Transfemoral aortic valve implantation of Edwards SAPIEN 3 without predilatation. Catheter Cardiovasc Interv  2017; 89: E38– 43. Google Scholar CrossRef Search ADS PubMed  5 Wendler O, Dworakowski R, Monaghan M, MacCarthy PA. Direct transapical aortic valve implantation: a modified transcatheter approach avoiding balloon predilatation. Eur J Cardiothorac Surg  2012; 42: 734– 6. Google Scholar CrossRef Search ADS PubMed  6 Fiorina C, Maffeo D, Curello S, Lipartiti F, Chizzola G, D’Aloia A et al.   Direct transcatheter aortic valve implantation with self-expandable bioprosthesis: feasibility and safety. Cardiovasc Revasc Med  2014; 15: 200– 3. Google Scholar CrossRef Search ADS PubMed  7 Grube E, Naber C, Abizaid A, Sousa E, Mendiz O, Lemos P et al.   Feasibility of transcatheter aortic valve implantation without balloon pre-dilation: a pilot study. JACC Cardiovasc Interv  2011; 4: 751– 7. Google Scholar CrossRef Search ADS PubMed  8 Conradi L, Schaefer A, Seiffert M, Schirmer J, Schaefer U, Schön G et al.   Transfemoral TAVI without pre-dilatation using balloon-expandable devices: a case-matched analysis. 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Google Scholar CrossRef Search ADS PubMed  12 Kappetein AP, Head SJ, Genereux P, Piazza N, van Mieghem NM, Blackstone EH et al.   Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2). Eur J Cardiothorac Surg  2012; 42: S45– 60. Google Scholar CrossRef Search ADS PubMed  13 Laborde J-C, Brecker SJD, Roy D, Jahangiri M. Complications at the time of transcatheter aortic valve implantation. Methodist DeBakey Cardiovasc J  2012; 8: 38– 41. Google Scholar CrossRef Search ADS PubMed  14 Alsabbagh MM, Asmar A, Ejaz NI, Aiyer RK, Kambhampati G, Ejaz AA. Update on clinical trials for the prevention of acute kidney injury in patients undergoing cardiac surgery. Am J Surg  2013; 206: 86– 95. Google Scholar CrossRef Search ADS PubMed  15 Gensas CS, Caixeta A, Siqueira D, Carvalho LA, Sarmento-Leite R, Mangione JA et al.   Predictors of permanent pacemaker requirement after transcatheter aortic valve implantation: insights from a Brazilian registry. Int J Cardiol  2014; 175: 248– 52. Google Scholar CrossRef Search ADS PubMed  © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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European Journal of Cardio-Thoracic SurgeryOxford University Press

Published: Apr 1, 2018

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