Avoiding S3 Valve Over-Sizing by Deployment Balloon Over-Filling: Impact on Rates of Permanent Pacemaker and Other Procedural Complications During TAVR

Abstract: Objectives. Patients with annular areas just above nominal S3 valve areas are at increased risk of over-sizing if a larger valve is implanted. We therefore evaluated the rate of permanent pacemaker (PPM) implantation associated with avoiding over-sizing by selective deployment balloon over-filling during transcatheter aortic valve replacement (TAVR) with the Sapien 3 (S3) valve. Methods. We included consecutive patients treated with the S3 valve from January 2016 to May 2017. We identified computed tomography annular areas where the nominally deployed valve would be over-sized by >12%-15% (areas 340-360 mm² for 23 mm valve, 420-450 mm² for 26 mm valve, 530-580 mm² for 29 mm valve) as those at highest risk for valve over-sizing. In these situations, we used the smaller valve and over-filled the deployment balloon to achieve a predicted valve area/annular area ratio of approximately 1. For annular areas >650 mm², we over-filled the 29 mm valve to achieve a similar ratio. Results. We evaluated 102 patients (59 males; mean age, 83.7 ± 6.5 years; mean STS score, 10.2). Over-filling of the deployment balloon was used in 35 cases (34%). We observed a post-TAVR PPM rate of 6.9% overall and 2.7% among the 75 patients without pre-TAVR right bundle-branch block (RBBB). Cases with valve over-filling vs nominal deployment had infrequent need for postdilation (14.3% vs 6.0%, respectively; P=.17) and similar postprocedure gradients (9.9 mm Hg vs 10.3 mm Hg, respectively; P=.59). Conclusion. A strategy to avoid S3 valve over-sizing by selective deployment balloon over-filling was associated with a low rate of PPM, especially in patients without pre-existing RBBB. 

J INVASIVE CARDIOL 2018;30(1):23-27.

Key words: aortic stenosis, transcatheter aortic valve replacement, permanent pacemaker

Permanent pacemaker implantation is one of the most frequent complications of transcatheter aortic valve replacement (TAVR).¹ Although the Sapien 3 (S3) transcatheter aortic valve (Edwards Lifesciences, Inc) has lower rates of paravalvular leak, stroke, and vascular complications compared to the Sapien XT device, the need for permanent pacemaker (PPM) is similar or higher (10.2% to 13.3% with S3).^2-4 Potential determinants of PPM requirements post TAVR include implantation depth, degree of over-expansion, and pre-existing conduction system disease.^5,6 A higher implantation of the S3 valve was associated with a reduced pacemaker requirement from over 19.2% to 9.2%.⁶ Therefore, a target depth of 80% aortic and 20% ventricular has been suggested with the S3 valve. 

The impact of valve over-sizing on pacemaker requirements is more controversial, with prior studies showing conflicting results.^5,6 Since the S3 valve is made in diameter sizes of 20, 23, 26, and 29 mm, patients with anatomy just above these diameters are particularly at risk for over-sizing if the next-larger valve is used. However, over-expansion of smaller valves to achieve higher than nominal areas has recently been reported.⁷ This approach may help to avoid valve over-sizing across the entire range of annular sizes. We therefore adapted the manufacturer’s recommended sizing matrix to prospectively over-fill the S3 deployment balloon and over-expand the valve frame in order to achieve a target valve area/annular area ratio of 1. We hypothesized that systematic avoidance of valve over-sizing by this “right-sizing” approach would lead to a low requirement for PPM implantation post TAVR.

Methods

Consecutive patients treated with an S3 valve were included in this evaluation. From January 2016 to October 2016, the use of the S3 valve at our institution (Hamilton Health Sciences, Hamilton, Canada) was based on special access application to treat patients with moderate or severe annular or outflow tract calcification or peripheral vascular disease. From November 2016 (when the device was approved in Canada) to May 2017, the S3 was used routinely. Patients with valve-in-valve intervention (n = 1) and patients treated with Sapien XT valve (n = 1) during this time were excluded from the analysis. The study was approved by the Hamilton Health Sciences Research Ethics Board.

Valve sizing and implantation. Preprocedure cardiac computed tomographic (CT) images reconstructed at end systole were used for valve-sizing decisions. Measurements were made of the annular area and in the device landing zone in the left ventricular outflow tract (LVOT) area (3-4 mm below the annular plane) using the 3mensio workstation (Medis).⁸ The extent of calcification in the annulus and LVOT was graded using a qualitative scale.⁹ The sizing matrix is shown in Supplemental Table S1. We used manufacturer recommendations for all predicted transcatheter valve area/annulus area ratios of up to 12%-15% over-sizing. For annuli with predicted oversizing >12%-15% (areas 340-360 mm² for 23 mm valve, 420-450 mm² for 26 mm valve, 530-580 mm² for 29 mm valve), we used the next smaller valve and over-filled the deployment balloon. In determining the over-filling volume, we were guided by prior data showing that the addition of 2 cc to the 23 mm valve can achieve an inflow area of 453 mm²; addition of 3 cc to the 26 mm valve can achieve an inflow area of 593 mm²; and addition of 4 cc to the 29 mm valve can achieve an inflow area of 740 mm².⁷ The reported mid-frame areas with balloon over-filling were smaller than the valve inflow and are listed separately in Supplementary Table S1. We assumed that lesser amounts of over-filling would result in proportionately less over-expansion of the valve frame. The actual volume used was also influenced by the extent of annular and LVOT calcification and the ratio of the annular area to the LVOT area. When there was heavy calcification or the ratio was <1, we tended toward less over-filling; when this ratio was >1, we tended toward more over-filling.

Both transfemoral and transapical approaches were used. Conscious sedation with percutaneous access was the default approach unless transesophageal echocardiographic guidance or difficult open femoral access was deemed necessary. The target implantation depth was 80% aortic and 20% ventricular. In the optimal co-planar angle, mid-balloon marker position was adjusted in the ventricular direction when over-filling was performed to account for possible increased S3 valve foreshortening in this scenario.

Image evaluation. The achieved implant depth was determined from the postprocedure angiogram. The overall length of the stent frame as well as the distance from the native aortic annulus to the inflow end of the stent frame were measured on the side of the stent frame oriented toward the left coronary cusp. The native aortic annulus was identified by tracing a line linking the sinuses of Valsalva.⁶ Implantation depth was expressed as a percentage of the aortic part of the stent frame in relation to the overall stent frame length. 

Postprocedure echocardiographic evaluation was performed by transthoracic echocardiography in all patients. Severity of paravalvular leak was graded as none, trace, mild, moderate, or severe.¹⁰ Interpretation was performed by expert readers blinded to all other patient data including angiographic findings and valve-sizing parameters. Follow-up CT imaging was not routinely performed, and was therefore only available for a few patients.

Clinical evaluation. Patients were followed with daily electrocardiograms and clinical assessments until hospital discharge. A clinic visit with electrocardiogram was performed at 30-45 days post procedure.

Statistical analyses. The distribution of baseline variables is presented using frequencies and percentage counts for categorical variables and as means ± standard deviations for continuous variables. Continuous and dichotomous variables were compared using 2-tailed t-tests and Chi-square tests, respectively. A series of univariate analyses was performed to evaluate factors that may be associated with PPM implantation, expressed as odds ratio (OR) with 95% confidence interval (CI) (JMP Pro 13; SAS Institute, Inc). 

Results

We evaluated 102 consecutive patients who were treated with TAVR. The population was elderly, with high-risk or inoperable severe aortic stenosis (Table 1). The mean STS score was 10.2 ± 5.9. Balloon deployment volume was nominal in 67 patients and over-filled in 35 patients. Treated mean annular areas and LVOT areas for the over-filled valves were larger than the predicted nominal valve area in all size categories (Table 2). The results of follow-up CT imaging in 2 patients with valve over-filling are shown in Figure 1. In both cases, the measured inflow and outflow areas are larger than the expected area that would have resulted from nominal valve deployment. 

Procedural characteristics are shown in Table 3. Most procedures were performed with conscious sedation (76.5%) and transfemoral percutaneous access (84.3%). Mean valve implantation depth as measured by quantitative angiography was 80.5%. Two-thirds of the TAVR patients were discharged day 1 post procedure (n = 68; 67%). Major adverse cardiovascular events, including death, stroke, and major vascular complications, were low.

PPM was required in 7 patients (6.9%) (Table 4). In all cases, the indication was third-degree heart block. Heart block developed during the procedure in 3 patients, on day 1 in 2 patients, on day 2 in 1 patient, and on day 3 in 1 patient. In patients without pre-existing right bundle-branch block (RBBB), the PPM implantation rate was 2.7%. Pacemakers were mostly required in patients with trifascicular block prior to TAVR. In univariate analysis, PPM was strongly associated with RBBB (OR, 36.5; 95% CI, 5.6-237.6), while the presence of annular calcification or implantation depth below 80% was not associated with PPM. Persistent left bundle-branch block was seen in 10.6% of patients without RBBB at baseline. 

There was no significant difference in the frequency of postdilation between nominal and over-filled valve deployments (Table 5). Paravalvular leak measured by postprocedure echocardiography was similar between groups, as was the postprocedure mean gradient.

Discussion

Among a consecutive series of 102 patients with high-risk or inoperable aortic stenosis treated with TAVR, a strategy to avoid S3 valve over-sizing by selective deployment balloon over-filling of smaller valves was associated with a very low rate of PPM implantation, especially in patients without pre-existing RBBB. Balloon over-filling vs nominal deployment appears to result in similar early procedural success. 

Although the need for PPM implantation post TAVR is influenced by multiple factors, valve expansion against the native anatomy likely plays a central role. Recent data show that at nominal volume, the inflow portion of the S3 valve frame expands to approximately 104% of the predicted valve area compared to mid-stent expansion of 99%.¹¹ Interaction of this larger inflow portion of the valve with the native annulus and LVOT likely contributes to the increased risk of PPM implantation with S3, particularly when implantation depth is low. Thus, reducing implant depth substantially reduces the need for PPM implantation with S3.¹² Prior studies have not shown a consistent impact of over-sizing, possibly because it is correlated with implant depth. Since the LVOT area is typically smaller than the annular area,¹³ the degree of over-sizing vs the native anatomy will increase as valve implant depth increases. In our study, we achieved an average implant depth of 80% aortic and avoided valve over-sizing in the deployment strategy. This reduced the need for PPM implantation compared to prior studies.^12,14 

In our cohort, 5 out of 7 PPM implantations required post TAVR were in patients with advanced conduction-system disease. It is likely that conduction disease and aortic stenosis share a common pathophysiology influenced by progressive annular and LVOT calcification.¹⁵ A monitoring study of TAVR patients for 24 hours prior to the procedure demonstrated that occult heart block or severe bradycardia are often identified and strongly predict the need for PPM implantation post procedure.¹⁵ Studies from the Partner 1 trial show that RBBB was the strongest predictor of PPM requirement after TAVR.^5,16 In our study, PPM was rare in patients without RBBB prior to TAVR; however, the need for PPM in patients with advanced conduction-system disease involving the right bundle remained high. In such patients, it is likely that the conduction system is very vulnerable to progression to complete heart block and that the requirement for PPM will not be substantially reduced by refinements in implantation technique. 

We observed that “right-sizing” was a technically successful implantation strategy, with similar procedural outcomes to nominal balloon filling. Prior studies have shown that risk of paravalvular leak is not as sensitive to the degree of annular over-sizing with the S3 device compared to the XT.^17,18 This is likely due to the presence of the external sealing cuff, which can fill in the gaps between the native annulus and valve frame.⁸ Our strategy for valve over-expansion was empiric and guided by CT data showing additional expansion of the S3 frame at all levels, but particularly at the inflow and outflow portions with balloon over-filling. For example, in a single-center study with CT follow-up, over-filling of the S3 resulted in 112% of the nominal area in the inflow of the valve compared to 96% for the XT.¹¹ Although we followed a prespecified scheme to choose additional balloon volume, the actual achieved dimensions under given over-filling conditions are likely quite variable. As with balloon-expandable coronary stents, important factors may include compliance of the native anatomy, duration and speed of inflation, and possible stent recoil. This raises the question of whether use of non-compliant balloon to deploy balloon-expandable valves can achieve more consistent sizing and better outcomes. 

Study limitations. This was a single-center study and these results may need validation in a multicenter study prior to wide adoption. Our approach to valve sizing requires a high level of confidence in the CT data on which the sizing decisions are made because substantial valve under-sizing could result if annular areas were under-estimated by CT. At our center, all CT images were reviewed by the primary TAVR operators to ensure that they were technically sufficient to guide valve-sizing decisions. Although we enrolled 102 patients and over-filled 35 valves, a larger number of recruited patients would provide greater certainty of the actual PPM implantation rate.

Conclusion

A strategy to avoid S3 valve over-sizing by selective deployment balloon over-filling of smaller valves was associated with a very low rate of PPM implantation, especially in patients without pre-existing RBBB. Balloon over-filling vs nominal deployment appears to result in similar acute procedural success rates.

References

1.    Urena M, Rodes-Cabau J. Permanent pacemaker implantation following transcatheter aortic valve replacement: still a concern? JACC Cardiovasc Interv. 2015;8:70-73.

2.    Rodriguez-Olivares R, van Gils L, El Faquir N, et al. Importance of the left ventricular outflow tract in the need for pacemaker implantation after transcatheter aortic valve replacement. Int J Cardiol. 2016;216:9-15.

3.    Thourani VH, Kodali S, Makkar RR, et al. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet. 2016;387:2218-2225.

4.    Kodali S, Thourani VH, White J, et al. Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis. Eur Heart J. 2016;37:2252-2262.

5.    Nazif TM, Dizon JM, Hahn RT, et al. Predictors and clinical outcomes of permanent pacemaker implantation after transcatheter aortic valve replacement: the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry. JACC Cardiovasc Interv. 2015;8:60-69.

6.    Mauri V, Reimann A, Stern D, et al. Predictors of permanent pacemaker implantation after transcatheter aortic valve replacement with the SAPIEN 3. JACC Cardiovasc Interv. 2016;9:2200-2209.

7.    Shivaraju A, Kodali S, Thilo C, et al. Overexpansion of the SAPIEN 3 transcatheter heart valve: a feasibility study. JACC Cardiovasc Interv. 2015;8:2041-2043.

8.    Schymik G, Schröfel H, Heimeshoff M, Luik A, Thoenes M, Mandinov L. How to adapt the implantation technique for the new SAPIEN 3 transcatheter heart valve design. J Interv Cardiol. 2015;28:82-89.

9.    Buellesfeld L, Stortecky S, Heg D, et al. Extent and distribution of calcification of both the aortic annulus and the left ventricular outflow tract predict aortic regurgitation after transcatheter aortic valve replacement. EuroIntervention. 2014;10:732-738.

10.    Kappetein AP, Head SJ, Genereux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Thorac Cardiovasc Surg. 2013;145:6-23.

11.    Kazuno Y, Maeno Y, Kawamori H, et al. Comparison of SAPIEN 3 and SAPIEN XT transcatheter heart valve stent-frame expansion: evaluation using multi-slice computed tomography. Eur Heart J Cardiovasc Imaging. 2016;17:1054-1062. Epub 2016 Mar 21.

12.    De Torres-Alba F, Kaleschke G, Diller GP, et al. Changes in the pacemaker rate after transition from Edwards SAPIEN XT to SAPIEN 3 transcatheter aortic valve implantation: the critical role of valve implantation height. JACC Cardiovasc Interv. 2016;9:805-813.

13.    Buellesfeld L, Stortecky S, Kalesan B, et al. Aortic root dimensions among patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. JACC Cardiovasc Interv. 2013;6:72-83.

14.    Husser O, Pellegrini C, Kessler T, et al. Predictors of permanent pacemaker implantations and new-onset conduction abnormalities with the SAPIEN 3 balloon-expandable transcatheter heart valve. JACC Cardiovasc Interv. 2016;9:244-254.

15.    Urena M, Hayek S, Cheema AN, et al. Arrhythmia burden in elderly patients with severe aortic stenosis as determined by continuous electrocardiographic recording: toward a better understanding of arrhythmic events after transcatheter aortic valve replacement. Circulation. 2015;131:469-477.

16.    Bagur R, Rodes-Cabau J, Gurvitch R, et al. Need for permanent pacemaker as a complication of transcatheter aortic valve implantation and surgical aortic valve replacement in elderly patients with severe aortic stenosis and similar baseline electrocardiographic findings. JACC Cardiovasc Interv. 2012;5:540-551.

17.    Yang TH, Webb JG, Blanke P, et al. Incidence and severity of paravalvular aortic regurgitation with multidetector computed tomography nominal area oversizing or undersizing after transcatheter heart valve replacement with the Sapien 3: a comparison with the Sapien XT. JACC Cardiovasc Interv. 2015;8:462-471.

18.    Blanke P, Pibarot P, Hahn R, et al. Computed tomography-based oversizing degrees and incidence of paravalvular regurgitation of a new-generation transcatheter heart valve. JACC Cardiovasc Interv. 2017;10:810-820.

From the ¹Department of Medicine, McMaster University, Hamilton, Ontario, Canada; ²Population Health Research Institute, Hamilton, Ontario, Canada; ³Harvard T.H. Chan School of Public Health, Boston, Massachusetts; ⁴Department of Surgery, McMaster University, Hamilton, Ontario, Canada; and ⁵Hamilton General Hospital, Hamilton, Ontario, Canada.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Sheth and Dr Natarajan report speaker’s bureau honoraria from Edwards Lifesciences. Dr Velianou reports speaker’s bureau honoraria and proctor fees from Edwards Lifesciences. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted August 28, 2017 and accepted September 8, 2017.

Address for correspondence: Tej Sheth, MD, DBCVSRI Building, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario, Canada, L8L 2X2. Email: shetht@mcmaster.ca