Sapien 3 Transcatheter Aortic Valve Implantation With Moderate or Without Predilation

Abstract: Objectives. Aortic valve preparation with balloon aortic valvuloplasty (BAV) has been previously considered mandatory during transcatheter aortic valve implantation (TAVI) procedures. BAV-inherent risks including stroke, conduction abnormalities, and reduced device profile size established the rationale for safe valve deployment without the need for aggressive valve preparation. We investigate the feasibility and safety of performing Sapien 3 (S3; Edwards Lifesciences) balloon-expandable TAVI with moderate or without predilation (PD). Methods. We examined consecutive patients with severe aortic stenosis who underwent S3-TAVI at our institution. Overall, 119 patients underwent TAVI without PD and 126 with moderate PD (mean valvuloplasty balloon diameter, 15.3 ± 2.1 mm). TAVI endpoints and adverse events were considered according to the Valve Academic Research Consortium (VARC)-2 definitions. Results. Device success for the entire cohort was 98.8%. PD rates were similar between groups. Total fluoroscopy time and amount of contrast used were lower in the no PD group (13 min vs 16.2 min [P<.001] and 71.3 mL vs 81 mL [P=.03], respectively). All-cause mortality up to 30 days was 0% (0/119) in the no PD group vs 1.6% (2/126) in the moderate PD group (P=.49). VARC-2 defined complication rates at 30 days including cerebrovascular accident were similar between groups. Overall, there was no significant difference in survival rate between both groups (hazard ratio, 3.6; 95% confidence interval, 0.80-16.2; P=.09). Conclusions. Balloon-expandable TAVI using the S3 device with moderate or without balloon PD is feasible and safe. Omission of PD in appropriate cases was associated with reduced fluoroscopy time and total contrast used without affecting procedural success.

J INVASIVE CARDIOL 2016;28(10):421-426

Key words: balloon aortic valvuloplasty, transcatheter aortic valve replacement, aortic stenosis

Transcatheter aortic valve implantation (TAVI) is a treatment option for inoperable or high-risk surgical patients with severe aortic stenosis (AS).^1,2 Performing balloon aortic valvuloplasty (BAV) before TAVI for preparation of the valve was previously considered mandatory, especially when using balloon-expandable valves. The rationale for performing BAV prior to TAVI is that it facilitates device introduction within the diseased aortic valve, enables an optimized expansion by reducing radial counterforces, and enables final measurement of the aortic annulus.³ Notwithstanding, BAV may result in stroke caused by distal embolization, atrioventricular conduction disturbances requiring permanent pacemaker implantation, and severe aortic regurgitation with intraprocedural hemodynamic instability.^4-6 Nonetheless, new-generation devices with reduced profile sizes, improved navigability, and strong radial forces allow safe valve deployment without the need for aggressive valve preparation. Utilization of imaging modalities such as computed tomography (CT) and three-dimensional (3D) echocardiography enables better annular and coronary height assessment, further minimizing the benefits of BAV during TAVI. Moreover, by avoiding aggressive predilation (PD), preservation of native aortic valvular complex architecture until valve deployment could conceivably facilitate better prosthetic anchoring. 

Previous reports of TAVI without PD included self-expandable valves,^7-9 transapical balloon-expandable valves,^10,11 or small case series of transfemoral balloon-expandable implantations.^12-14 Moderate PD during TAVI was examined in a previous report that included self-expandable valves.¹⁵ We recently published our experience of performing Sapien and Sapien XT balloon-expandable TAVI with moderate PD vs no PD.¹⁶ One recent report on the new generation of balloon-expandable valves suggested an increased risk of cerebral embolization after direct implantation of the valve.¹⁷ The purpose of the present article is to assess the feasibility and safety of performing Sapien 3 (S3; Edwards Lifesciences) TAVI with moderate or without PD. 

Methods

We examined all consecutive patients with severe symptomatic AS who underwent S3 TAVI at our institution. All patients had congestive heart failure with New York Heart Association (NYHA) class II-IV symptoms. Aortic valve disease was assessed initially with transthoracic echocardiography followed by an electrocardiography-gated, multislice CT angiography study with a Somatom Cardiac 64 scanner (Siemens Medical Solutions). Aortic valve calcification was quantified by a standard Agatston methodology for all available non-contrast CT scans, with a threshold for calcium detection set at 130 Hounsfield units.¹⁸ Prosthetic valve size selection was based on CT or immediate preprocedural 3D transesophageal echocardiography (TEE). All patients were considered suitable for TAVI by our institutional heart team. Vascular access approach was chosen on the basis of each patient’s risk profile. Following valve deployment, TEE was used to assess the severity of paravalvular leak (PVL). Baseline clinical, echocardiographic, and procedural details for TAVI were recorded for all patients, including 1-month clinical and echocardiographic assessments during a follow-up visit. TAVI endpoints, device success, and adverse events were considered according to the Valve Academic Research Consortium (VARC)-2 definitions.¹⁹ The study was approved by the Institutional Review Board at our hospital and informed consent was obtained from all subjects.

Moderate vs no predilation. A “regular” PD approach included utilization of 20 mm, 23 mm, and 25 mm valvuloplasty balloons for 23 mm, 26 mm, and 29 mm valves, respectively. During the last 4 years, we perform TAVI at our institute using moderate or no PD approaches. The moderate PD group included patients who underwent BAV during TAVI using small-sized balloons. It included Z-med II balloon (B. Braun Interventional Systems) with a diameter of ≤18 mm for the 23 mm implanted valves and of ≤22 mm for the 26 or 29 mm implanted valves. In the no PD group, intraprocedural BAV was omitted. BAV was performed according to standard techniques via retrograde femoral approach and with rapid pacing during balloon inflation. The decisions regarding moderate or no PD as well as valvuloplasty balloon size were left to operator discretion. Indications for moderate PD instead of direct TAVI were severe or asymmetric calcification of the aortic valve, small aortic valve area (<0.5 cm²), and bicuspid aortic valve anatomy. 

Statistical analysis. All data were summarized and displayed as mean ± standard deviation for continuous variables and as number (percentage) of patients in each group for categorical variables. The Student’s t-test and Pearson’s χ² test or Fisher’s exact test were used to evaluate statistical significance between continuous and categorical variables, respectively. A predictive model for moderate vs no PD, incorporating variables associated to a significance level of <.10 was designed. This model was used to generate a propensity score for moderate vs no PD. Receiver operating characteristic analysis was used to assess the predictive value of this model for moderate vs no PD. A Cox proportional hazards model was used to assess overall survival. The propensity score was then added to a binary logistic model in order to assess the influence of moderate vs no PD on the likelihood of PVL ≥ mild, postdilation, new permanent pacemaker implantation, 30-day major complication rate, 1-year mortality, fluoroscopy time >15 minutes and contrast utilization >90 mL. All of the analyses were considered significant at a 2-tailed P-value of <.05. The SPSS statistical package v. 20.0 was used to perform all statistical evaluations (SSPS, Inc).

Results

A total of 246 patients underwent S3 TAVI at our institute. We excluded from analysis 1 patient who had “regular” PD (25 mm balloon valvuloplasty before a 26 mm valve implantation). Of the remaining 245 patients, a total of 119 underwent TAVI with no PD and 126 underwent TAVI with moderate PD. The mean follow-up period was 8.1 ± 4.4 months. Transfemoral approach was used in 96.7% of the cases, transapical approach in 1.2%, and transaortic approach in 2%. The baseline clinical characteristics and pre-TAVI imaging details of the study population are shown in Table 1. Percentage of males was lower in the no PD group (52.9% vs 66.7%; P=.03) and frequency of previous stroke was higher (15.1% vs 4.8%; P=.01) compared with patients in the moderate PD groups. Echocardiography demonstrated significantly higher mean/peak aortic valve area and smaller aortic valve pressure gradients in the no PD group, and their CT analysis demonstrated significantly smaller mean annulus diameter and area (Table 1). Data on aortic valve CT calcification scoring were available for 222 out of 245 patients. Average calcification score was 2564 ± 1761 Agatston units (AU) in the no PD group vs 4016 ± 1812 AU in the moderate PD group (P<.001).

The mean valvuloplasty balloon diameter in the moderate PD group was 15.3 ± 2.1 mm. The mean PD valvuloplasty balloon diameter/CT mean annulus diameter was 0.62 ± 0.09. In the moderate PD group, balloon size did not exceed the minor axis dimension of the aortic annulus in any of the 126 cases. The range of balloon diameters used for each valve size implanted is shown in Figure 1. Procedural details are shown in Table 2. There were no significant differences between valve size or vascular access site between the groups. Device success rate was 100% (119 of 119) for the patients in the no PD group compared with 97.6% (123 of 126) for the moderate PD group (P=.09). Postdilation was performed in 10 patients in the no PD group (8.4%) and 6 patients in the moderate PD group (4.8%; P=.25). We did not encounter any difficulty crossing the native valve with the bioprosthesis mandating utilization of buddy-balloon technique or retraction of the delivery system and performing BAV. Total fluoroscopy time was significantly lower in the no PD group (13 ± 5.5 min vs 16.2 ± 6.6 min; P<.001). Total amount of contrast used was significantly lower in the no PD group (71.3 ± 31 mL vs 81.0 ± 36.4 mL; P=.03). There were similar rates of postprocedural PVL in both groups: 83.2%, 16.8%, 0%, and 0% vs 87.3%, 11.1%, 1.6%, and 0% for no/trace, mild, moderate, and severe PVL, respectively (P=.48). All 3 cases of device failure were due to moderate PVL post procedure.

All-cause mortality up to 30 days was 0% (0/119) in the no PD group vs 1.6% (2/126) in the moderate PD group (P=.49). Thirty-day complications according to VARC-2 including cerebrovascular accident/transient ischemic attack (CVA/TIA) were similar between groups (Table 3). Overall, there was no significant difference in survival rates between patients who underwent TAVI with moderate PD compared with patients who underwent TAVI without PD (hazard ratio [HR], 3.6; 95% confidence interval [CI], 0.80-16.2; P=.09) (Figure 2). 

Multivariate analysis. A predictive model for moderate vs no PD incorporating variables associated to a significance level of <.10 had a strong predictive value for this parameter (area under the curve, 0.80; 95% CI, 0.74-0.86; P<.001). These variables included gender, previous stroke, peripheral artery disease, aortic valve area, mean aortic valve area gradient, mean aortic valve annulus diameter, and aortic valve calcification score. This model was used to generate a propensity score for moderate vs no PD. With adjustment using this score, there was still no difference in the likelihood of PVL ≥ mild, postdilation, new permanent pacemaker implantation, 30-day major complication rate, and 1-year mortality for moderate vs no PD (Table 4). With adjustment, there was still a significant difference in fluoroscopy time >15 minutes and in contrast utilization >90 mL.

Discussion 

A total of 119 patients had TAVI without PD and 126 had TAVI with moderate-sized valvuloplasty balloons. We found high device success rate in both groups, with shorter fluoroscopy time and lower amount of contrast used in the no PD group. We also found similar short-term major complication rates for both groups that are comparable with previous reports. The results of the present study indicate that performing S3 balloon-expandable TAVI with moderate or without PD is feasible and safe.

BAV has been previously considered as a mandatory step during TAVI.⁷ It is used mainly to increase the aortic valve orifice and therefore to facilitate the introduction of the device within the diseased aortic valve, to reduce radial counterforces thus optimizing prosthesis expansion, and to help in the final assessment of annular dimensions and rule out coronary obstruction just before valve implantation.³ Performing PD with large-diameter balloons has been associated with increase in embolic adverse events, conduction abnormalities, and acute hemodynamic instability due to acute severe aortic insufficiency.^4-6 New-generation devices with reduced profile sizes and increased radial forces, as well as advancement in pre-TAVI imaging techniques, have set the framework for performing TAVI with moderate PD or without PD.^{7-13,15,20,21} 

TAVI without PD was first reported by Grube et al in 2011.⁷ Their study included 60 patients treated with transfemoral self-expandable TAVI. These patients had high success rate, low permanent pacemaker implantation rate, similar acute hemodynamic effects, and lower PVL rates compared with their historical cohort that had TAVI with “regular” PD. Omission of BAV was described in 50 patients undergoing transapical balloon-expandable TAVI and was found to be effective and safe.¹⁰ Direct transfemoral balloon-expandable TAVI was evaluated in small case series^12-14,20 and in a series that included both self-expandable and balloon-expandable valves (n = 28 vs 51, respectively).²¹ Although the number of patients was limited, the procedural success rate and short-term complications were acceptable in all of these reports. We recently published our experience performing Sapien and Sapien XT balloon-expandable TAVI with moderate or no PD.¹⁶ Overall, 121 patients underwent TAVI with no PD and 392 with moderate PD in this series with similar clinical outcomes between both groups. Interestingly, Bijuklic et al¹⁷ found that balloon-expandable TAVI without PD was associated with a significantly higher volume of cerebral ischemic lesions in postprocedural diffusion-weighted magnetic resonance imaging. After excluding 4 patients who had periprocedural stroke, they compared 32 patients who had TAVI with PD (19 cases of Sapien XT and 13 cases of S3 implantation) with 55 patients who had S3 TAVI without PD. This recent study raised concern regarding the safety of performing S3 TAVI without PD, but had several limitations such as small number of patients, comparison of the no PD group to a historical control group, and a significant difference in timing of magnetic resonance imaging after TAVI. In the present study, we did not find any difference in the clinical outcome when omitting PD before S3 valve implantation. 

We found several differences in baseline characteristics differences between groups in the present study. The patients in the no PD group had a lower proportion of males. Pre-TAVI imaging revealed larger aortic valve areas and lower pre-TAVI gradients, lower mean aortic annulus diameter and area, and lower mean aortic valve calcification score for the patients in the no PD group. This should be attributed to the fact that the decision to perform TAVI with moderate or without PD was left to the discretion of the operator and was based on the comprehensive pre-TAVI evaluation and tailored for each patient. Since the introduction of the direct TAVI approach, concerns have been raised for omitting BAV – especially in cases of bulky calcified aortic valve, valve area <0.4 cm², eccentric residual valvular orifice, and larger bioprostheses.^3,12,21,22 Preprocedural imaging evaluation of the native aortic valve, including calcification severity, homogeneity of the calcification within the valve apparatus, severity of AS, and valve anatomy (eg, symmetric tricuspid valve vs asymmetric bicuspid valve) were the factors that helped us decide whether to use the direct approach or to moderately predilate the valve. 

Device success among our patients was high and similar between groups (overall, 98.8%). Not surprisingly, by omitting PD, we were able to significantly decrease fluoroscopy time (13 vs 16.2 min; P<.001) and amount of contrast used (71.3 mL vs 81 mL; P=.03). Omitting PD did not result in a significantly increased need to perform postdilation (8.4% in the no PD group vs 4.8% in the moderate PD group; P=.25). The postprocedural PVL rates were similar between groups in both univariate and multivariate analyses (Table 4). A trend for lower postdilation rates and lower residual PVL following direct TAVI has been demonstrated in the past.^7,8 Interestingly, in our cohort, the significantly lower aortic valve calcification scores of patients in the no PD group (2564 AU vs 4016 AU; P<.001) did not lead to a lower rate of postprocedural PVL. It has been recently shown by our group as well as by others that amount of aortic valve calcification highly correlates with severity of PVL and frequency of postdilation after balloon-expandable TAVI.^23,24 Nonetheless, the lower overall PVL rates after S3 implantation demonstrated in the present study and a study by Webb et al²⁵ may have diminished the expected difference between the relatively lower-calcification no PD group and the higher-calcification moderate PD group in our cohort. 

The safety of omitting large-sized valvuloplasty balloons is further reinforced by our short-term mortality and major complication rates. The overall 30-day mortality rate of 0.8%, CVA/TIA rate of 2.4% (0% in the no PD group; P=.25), and myocardial infarction rate of 0% are comparable to the previously published experience with new-generation valves.^25-27

Permanent pacemaker implantation rates at 30 days were similar in both groups. Lange et al examined 237 patients who underwent self-expandable TAVI and found a new permanent pacemaker implantation rate of 27.1% in patients who underwent BAV during TAVI with 25 mm balloon compared with 15.4% in patients treated with smaller balloons (P=.04).¹⁵ Our series included only new-generation balloon-expandable valves, which have a lower risk of pacemaker implantation compared with self-expandable valves.²⁸ Moreover, the moderate PD approach in the present study included much smaller valvuloplasty balloons compared with the previous series described above (15 mm vs 21.3 mm) without any case of a PD balloon larger than the minor axis of the aortic annulus, thus the balloon likely not making contact with the aortic annular margins. 

Study limitations. The present study represents a retrospective, non-randomized, single-center experience. The decision between approaches as well as PD valvuloplasty balloon size selection were left to the discretion of the operator and were not based on prospective solid inclusion criteria for each of the two approaches. Moreover, patients undergoing TAVI without PD constituted a highly selective group with higher valve area, lower valve gradients, less calcification, and a symmetric calcification pattern. Therefore, the results of the no PD group must not be generalized. Nonetheless, during the study period, a total of 245 patients underwent balloon-expandable TAVI with moderate or no PD and had a high procedural success rate and low overall complication rates. Randomized trials evaluating the effects of regular, moderate, and no PD are needed to provide insights into the differences between various intensities of valve preparation and to determine the criteria for the safe utilization of each approach. 

Conclusion

S3 balloon-expandable TAVI with moderate or without balloon PD is feasible and safe. Omission of PD in selected cases with non-severe and symmetric calcification, tricuspid aortic valve morphology, and aortic valve area ≥0.5 cm² was associated with reduced fluoroscopy time and total contrast used without affecting procedural success.

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From the Cedars-Sinai Heart Institute, Los Angeles, California.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Makkar reports grant support from Edwards Lifesciences and St. Jude Medical; consultant fees from Abbott Vascular, Cordis, and Medtronic; equity in Entourage Medical. Dr Jilaihawi reports consultant fees from Edwards Lifesciences, St. Jude Medical, and Venus MedTech. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted May 13, 2016, provisional acceptance given June 9, 2016, final version accepted June 14, 2016.

Address for correspondence: Yigal Abramowitz, MD, Heart Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Boulevard, AHSP, Suite A3600, Los Angeles, CA 90048. Email: yigalab@yahoo.com