Hemodynamic Outcome and Valve Durability Beyond Five Years After Transcatheter Aortic Valve Replacement

Abstract: Objective. The aim of this study was to evaluate hemodynamic outcome, structural valve deterioration, and bioprosthetic valve failure beyond 5 years after transcatheter aortic valve replacement (TAVR). Methods. Demographic, procedural, and outcome data were obtained from all patients treated with TAVR at our institution from 2006 to 2012. We included all patients with echocardiographic data at baseline and with a follow-up echocardiography more than 5 years after TAVR. Standardized definitions were used to assess durability of transcatheter aortic valves. Results. A total of 452 patients were treated with apical or transfemoral transcatheter aortic valve implantation (TAVI) from 2006-2012, and 103 (23%) patients were still alive more than 5 years post TAVI. Mean duration of follow-up was 7.0 ± 0.9 years, with a maximum duration of 9.8 years. Seventy-nine of the 103 patients (76.7%) underwent follow-up echocardiography. Mean aortic gradient decreased from 51.8 ± 14.3 mm Hg before TAVR to 11.7 ± 5.8 mm Hg after TAVR (P<.001), and remained stable at 10.6 ± 6.3 mm Hg during late follow-up (P=.26). Bioprosthetic valve failure occurred in 3 patients (3.8%); two of these patients required reintervention. Seven patients (8.9%) had moderate structural valve deterioration, and 1 patient (1.3%) had severe structural valve deterioration. Conclusion. TAVR with self-expanding and balloon-expandable valves appears to be a long-lasting treatment strategy for severe aortic stenosis with excellent long-term hemodynamic function and very low incidence of structural valve deterioration and bioprosthetic valve failure. 

J INVASIVE CARDIOL 2020;32(3):82-87.

Key words: long-term outcomes, valve failure

Transcatheter aortic valve replacement (TAVR) is an established procedure and has become the standard treatment for inoperable and surgical high-risk/intermediate-risk patients with severe symptomatic aortic stenosis.^1-3 Increased operator experience, improved transcatheter valve systems, and better patient selection have made the procedure more feasible and suitable for a broader patient population.⁴ Recently, large randomized trials comparing TAVR with surgical aortic valve replacement (SAVR) in low-risk patients have reported excellent results favoring TAVR during short-term follow-up.^5,6 

Since the indication for TAVR is now expanding to younger patients with fewer comorbidities, the question about long-term durability becomes paramount. Only a few small studies have explored the long-term durability of bioprosthetic valves in patients after TAVR.^3,7-10 Five-year data from the randomized PARTNER 1 trial presented no indication of structural valve deterioration (SVD).³ In addition, data from the United Kingdom TAVR registry demonstrated that 91% of patients remained free from SVD between 5 and 10 years after implantation.⁹ Compared with the very long-term experience after SAVR, data on long-term outcomes after TAVR are still very limited.

In the present study, we report our long-term experience in treating patients with aortic stenosis using the TAVR technique. The aim of this study was to assess hemodynamic outcomes, and to evaluate the incidence of SVD and bioprosthetic valve failure (BVF) in patients who underwent TAVR from 2006-2012.

Methods

Study population and design. Between November 2006 and December 2012, a total of 452 patients with severe symptomatic aortic stenosis underwent TAVR using the transfemoral or transapical approach. After checking survival status, patients were contacted by telephone and invited for a follow-up visit between May 2018 and February 2019. All living patients who underwent TAVR >5 years ago were included in our study regardless of access route or valve type. Patients were excluded from the study if they refused to undergo follow-up echocardiography, or if they were not able to visit our institution due to severe physical or mental impairment. Systematic clinical and echocardiographic data were obtained for all eligible patients; in patients who were not able to come to our hospital, data were obtained from the referring cardiologist. The last available echocardiographic evaluation was considered for our analysis. The study was approved by the local ethics committee of the Goethe University of Frankfurt, and conducted in accordance with the Declaration of Helsinki. 

Procedure. Design features of balloon-expandable and self-expanding bioprostheses, as well as technical details of the procedure, have been previously described.^11,12 The Edwards Sapien prosthesis (Edwards Lifesciences), available in 23 mm, 26 mm, and 29 mm, was implanted via the transfemoral or the transapical approach. The CoreValve prosthesis (Medtronic), available in 26 mm, 29 mm, and 31 mm sizes, was implanted via the transfemoral approach. Three patients received a JenaValve (JenaValve Technology) via the transapical approach; two of these patients died before follow-up, so only 1 patient with a 25 mm size JenaValve was included for further analysis. All procedures were performed under local or general anesthesia with endotracheal intubation.

Definitions. As recently published by Capodanno et al,¹³ moderate SVD was defined as mean transprosthetic gradient ≥20 mm Hg and <40 mm Hg, and/or ≥10 mm Hg and <20 mm Hg change from baseline, and/or moderate new or worsening intraprosthetic aortic regurgitation (AR). Severe SVD was defined as mean gradient ≥40 mm Hg, and/or ≥20 mm Hg change from baseline, and/or severe intraprosthetic AR. BVF was defined as repeated intervention or severe SVD. In addition, BVF included autopsy findings of bioprosthetic valve dysfunction, likely related to the cause of death, or valve-related death. 

Statistical analysis. Descriptive statistics were summarized as mean ± standard deviation for normally distributed continuous variables or otherwise as median with interquartile range (IQR, 25th-75th percentile). Categorical variables were described by frequencies and percentages. Differences in paired samples were tested using Wilcoxon signed-rank test or paired Student’s t-test. Categorial variables were compared using Chi-square or Fisher’s exact test. Multivariate regression analysis was performed to detect predictors of BVF and SVD. Statistical significance was defined at a level of α≤.05. Analyses were performed with SPSS, version 24 (SPSS, Inc).

Results

From November 2006 to December 2012, a total of 452 patients were consecutively treated with TAVR at our institution. Of these patients, a total of 335 (74.1%) died before the time of inclusion, seven patients were lost to follow-up, and 7 cases of implantation were not successful (implantation success rate, 98.2%). Thus, a total of 103 patients (22.8%) were alive and eligible for our study. The mean follow-up time was 7.0 ± 0.9 years, with a maximum duration of 9.8 years. Seventy-nine of the 103 patients (76.7%) underwent late follow-up echocardiography (Figure 1). Baseline and procedural characteristics, as well as early clinical outcomes, are presented in Tables 1 and 2. Mean age was 80.1 ± 7.9 years, and 56.3% were women. Most patients were highly symptomatic, with 67.0% in New York Heart Association (NYHA) class III or IV, and a mean logistic EuroScore of 18.1 ± 11.7%. The devices used were balloon-expandable Edwards Sapien valves in 58.8% and self-expanding CoreValves in 40.2%. Only 1 patient received a self-expanding JenaValve, and we were unable to identify the valve type in 1 other patient. Transfemoral approach was used in 65.0% of cases and transapical approach was used in 35.0% of cases. Early clinical outcomes data revealed low complication rates according to Valve Academic Research Consortium (VARC)-2 criteria (Table 2).

Baseline echocardiographic characteristics, as well as prosthesis performance at discharge and late follow-up, are listed in Table 3. Aortic stenosis was severe at baseline, with a mean gradient of 51.8 ± 14.3 mm Hg and an aortic valve area (AVA) of 0.71 ± 0.19 cm². Moderate or severe AR was present in 9 patients (9.1%) at baseline. Mean time of follow-up echocardiography was 6.2 ± 1.5 years. Mean aortic gradient decreased from 51.8 ± 14.3 mm Hg before TAVR to 11.7 ± 5.8 mm Hg post TAVR (P<.001) and remained low at 10.6 ± 6.3 mm Hg at late follow-up (P=.26)  (Figure 2). AVA increased from 0.71 ± 0.19 cm² to 2.08 ± 0.91 cm² at late follow-up (P<.001). AVA was not evaluated at discharge. Prevalence of moderate and severe AR was not significantly higher at late follow-up than at discharge, but the P-value of .052 indicates a trend toward higher AR rates at late follow-up (12.6% to 7.8%; P=.052) (Figure 3). BVF occurred in 3 patients (3.8%). Among those, two patients required reintervention. Moderate SVD occurred in 7 patients (8.9%), and severe SVD was observed in 1 patient (1.3%). 

Detailed echocardiographic analyses of patients who presented with SVD and/or BVF are shown in Table 4. Of the 2 patients who needed reintervention, patient #1 had transapical implantation of a 23 mm Edwards Sapien valve and presented with bioprosthetic valve thrombosis 2 years post implantation, leading to open-heart surgery with implantation of a 23 mm Carpentier-Edwards Perimount valve (Edwards Lifesciences). Patient #2 received a 29 mm CoreValve via transfemoral approach and had endocarditis 2 years post TAVI; this patient had multiple septic embolisms, and the bioprosthetic valve was replaced with a surgically implanted BioValsalva aortic valve conduit (Vascutek Terumo). Both patients are currently alive and asymptomatic. Only 1 patient (#3) patient had severe hemodynamic SVD with severe AR. No treatment was recommended in this case since the patient had multiple severe comorbidities. Seven patients (#4 through #10) had new moderate SVD at follow-up. Among them, five had moderate AR, one patient (#10) had a progressive elevation of mean gradient, and 1 patient (#9) had a combination of progressive elevation of mean gradients and moderate intraprosthetic AR. In the multivariate regression analysis, we found no significant predictor for BVF or SVD (Table 5).

Discussion

The purpose of our study was to explore the long-term (>5-year) durability of bioprosthetic aortic valves implanted with the transcatheter approach using a standardized definition of SVD and BVF. Our findings indicate that balloon-expandable (Edwards Sapien) and self-expanding (CoreValve) valves have very good durability, with low SVD and BVF rates. The unanswered issue of long-term valve durability is probably the key challenge in expanding TAVR to low-risk and younger patients. Data on durability are limited, since the procedure is still very young and the patients first treated with this technique were very old, with many comorbidities. In the PARTNER I trial, no SVD requiring SAVR was detected after 5 years and the mean transvalvular gradient valve area remained stable.^2,3 Recently, a single-center French study reported very good durability of transcatheter balloon-expandable valves at 8 years, with SVD and BVF rates at 3.2% (95% confidence interval [CI], 1.45-6.11) and 0.58% (95% CI, 0.15-2.75), respectively.⁸ Most recently, data from the U.K. TAVI registry⁹ demonstrated very low incidence of moderate SVD (8.7%) and severe SVD (0.4%). Likewise, Sondergaard et al¹⁰ recently reported a very low 6-year SVD rate of 4.8% in the NOTION trail. The results of our study confirm these previous reports and expand the knowledge about the durability of balloon-expandable and self-expanding valves beyond 5 years. By multivariate regression analysis, we could not find any predictors for BVF or SVD. However, the logistic model may have been influenced by small sample size bias and low event rate. In the future, larger trials must investigate whether there are any significant predictors for BVF or SVD, such as valve size, prosthesis mismatch, chronic renal insufficiency, or amount of calcification.

In contrast to the rather young technique of TAVR, very long-term durability of aortic valves after SAVR has been evaluated in many previous studies.^14-16 For instance, the Carpentier-Edwards Perimount aortic valve showed excellent durability in a large cohort, with reoperation rates of 1.9% and 15% at 10 and 20 years, respectively.¹⁴ The very long-term incidence of SVD and aortic valve reintervention was very low in most surgical device studies, but some devices (such as the Sorin Mitroflow bioprosthesis) presented a high rate of severe SVD (8.4%) only 5 years after surgery.¹⁷ Therefore, it is necessary to evaluate all bioprosthetic valves individually — especially transcatheter devices, since they consist of a combined stent and bioprosthesis, which may affect long-term durability differently than SAVR valves. TAVR valves are crimped prior to replacement to allow transcatheter delivery. Electron microscopic analysis has demonstrated that crimping and ballooning injures the pericardium.^18,19 Furthermore, TAVR valves are implanted without removing the native annular calcification, which may lead to a non-circular deployment of the stent, and could potentially result in less effective coaptation of the leaflets.^20,21 Additionally, subclinical leaflet thrombosis leading to elevated transprosthetic gradients and worse clinical outcomes seems to occur more frequently in TAVR patients than SAVR patients.²² Interestingly, in spite of these rather unfavorable TAVR characteristics, the Danish NOTION trial demonstrated that the incidence of SVD was significantly less in TAVR patients than in SAVR patients through 6 years (24.0% vs 4.8%, respectively; P<.001).¹⁰ BVF rate was low and similar in both groups (6.7% vs 7.5%, respectively; P=.89). Larger, longer-term studies are warranted to confirm the results of the small, randomized NOTION trial. 

Study limitations. First, the present study is a retrospective, single-center investigation with a fairly limited number of patients. Second, echocardiographic parameters were not evaluated by a central independent core laboratory, and local investigators may not have performed the measurements according to a standardized protocol. Third, our study on long-term effects after TAVR partly refers to the first-generation transcatheter valves that were implanted by operators still on their learning curve for TAVR procedures. Further studies are needed to assess long-term outcomes after TAVR with next-generation devices. The final limitation of our study is that only 22.8% of all patients who underwent TAVR between 2006 and 2012 were still alive after the mean follow-up period of 7.0 years; therefore, survival bias may have influenced our results. 

Conclusion

Information about the durability of transcatheter valves is paramount, since the indication for TAVR is currently extending to younger and healthier patients. Our study confirms that TAVR is a lasting treatment strategy for severe aortic stenosis, with sustained hemodynamic performance in prostheses and low SVD and BVF rates. 

From the Departments of ¹Cardiology and ²Cardiothoracic Surgery, University Hospital Frankfurt am Main, Germany. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Vasa-Nicotera reports proctor income from Abbott, Medtronic, Boston Scientific, and Edwards Lifesciences. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted August 30, 2019, final version accepted September 12, 2019.

Address for correspondence: Marie-Isabel Murray, MD, MSc, Department of Cardiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Email: marie-isabel.murray@kgu.de

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