Transcatheter Aortic Valve-In-Valve Implantation: Clinical Outcome as Defined by VARC-2 and Postprocedural Valve Dysfunction According to the Primary Mode of Bioprosthesis Failure

Abstract: Objectives. The objectives of this study were to investigate: (1) the clinical outcome of transcatheter aortic valve-in-valve (VIV) implantation according to Valve Academic Research Consortium (VARC)-2 criteria; and (2) to determine whether postprocedural transvalvular gradients differ in patients with bioprosthesis regurgitation or stenosis as primary mode of failure. Background. Transcatheter aortic VIV implantation has become a feasible option for selected high-risk patients with failed aortic surgical bioprostheses. Methods. Transcatheter aortic VIV implantation was performed in 14 high-risk individuals at the University of Zurich and University College London. Results. The prosthesis was successfully implanted in 13 patients (93%). In 1 patient, a second transcatheter valve needed to be implanted due to valve malpositioning. Thirty-day all-cause mortality was 7% (1/14). Prosthetic valve dysfunction according to VARC-2 at 30 days was observed in 7/14 patients (50%) due to an increased postprocedural transvalvular gradient >20 mm Hg. Preprocedural transaortic gradients correlated significantly with postprocedural gradients (r=0.91; P<.001). At 30-day follow-up, postprocedural gradients were higher in patients with aortic stenosis as primary mode of failure as compared to those with aortic regurgitation (36 ± 6 mm Hg vs 16 ± 4 mm Hg; P=.01). None of the patients exhibited prosthetic valve regurgitation of more than mild degree. Conclusion. The feasibility and safety of VIV implantation in failed aortic bioprostheses is demonstrated. A higher postprocedural gradient was observed after VIV implantation in patients with aortic stenosis as compared to regurgitation as primary mode of failure. 

J INVASIVE CARDIOL 2014;26(10):542-547

Key words: percutaneous valve therapy, valvular surgery, bioprosthesis

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Surgical aortic valve replacement (SAVR) is considered the standard treatment for symptomatic aortic stenosis (AS) due to its excellent short- and long-term outcome.^1,2 Nevertheless, despite proven safety and efficacy, bioprosthetic valves may deteriorate over time, and redo open-heart surgery might become necessary. Redo isolated SAVR can safely be performed in most patients with low perioperative risk.³ However, as bioprostheses are mainly utilized in an elderly patient population, these patients are often at high perioperative risk due to significant comorbidities or previous coronary artery bypass graft surgery.^4,5 A substantial number of elderly patients with failed bioprostheses are probably not referred to redo SAVR given their increased surgical risk.

Over the last decade, transcatheter aortic valve implantation (TAVI) has been established as an alternative less invasive treatment in patients with symptomatic AS and high surgical risk.^6-9 With the success of TAVI, valve-in-valve (VIV) procedures have become available as a new treatment option for high-risk individuals with failed surgical bioprostheses.^10-12 The technical feasibility of both transapical and transfemoral transcatheter VIV procedures into failed surgical prostheses has been suggested in different registries.^12-18 However, experience with this technique is still limited. Comprehensive outcome assessment and data reporting is paramount, in particular with the implementation of novel techniques. Most recently, the Valve Academic Research Consortium (VARC) proposed the revisited standardized consensus definitions (VARC-2) for outcome reporting in transcatheter valves.^19,20

The aim of the present study was to report the University of Zurich and the University College London transcatheter aortic VIV experience according to the recently revised VARC-2 consensus criteria.²⁰ Moreover, we aimed to determine in our cohorts whether postprocedural gradients were different in patients with bioprosthesis stenosis as compared to regurgitation as primary mode of failure. 

Methods

Patients. At the University Hospital Zurich, a total of 353 patients underwent TAVI from May 2008 to October 2012.²¹ At the Heart Hospital London (University College London), a total of 150 TAVI procedures were performed from April 2010 to October 2012. Transcatheter aortic VIV implantation was performed in 9 high-risk individuals at the University Hospital Zurich, and in 5 high-risk individuals at the Heart Hospital London due to failed aortic bioprostheses. At both institutions, all patients were evaluated by a multidisciplinary Heart Team consisting of interventional cardiologists, cardiothoracic surgeons, anesthesiologists, and cardiac imaging specialists. The patients were considered not amenable to redo open-heart surgery due to significant comorbidities.  Written informed consent was obtained from all patients. The study was approved by the local ethics committee. 

Valve-in-valve implantation procedure. Transthoracic (TTE) and transesophageal echocardiography (TEE), cardiac catheterization, and multislice computed tomography (MSCT) of the aortic root and the aortoiliofemoral system were performed before the procedures. All procedures were performed under general anesthesia as previously described.^9,22-24 In transfemoral procedures, percutaneous access was gained by direct puncture of the common femoral artery, in transapical procedures by puncture of the apex via mini-thoracotomy. Selection of the prosthesis size was aided by measurements of the internal diameter of the failed surgical bioprosthesis. In 12 patients, measurements of the maximal and minimal internal diameters of the bioprosthesis were performed on preprocedural MSCT images. In the remaining 2 patients, transcatheter valve sizing was mainly based on reported internal diameters and on periprocedural TEE images and aortic angiograms. For quantitative MSCT analysis, the centerline of the aortic root and the ascending aorta was drawn semi-automatically using dedicated commercially available software (3mensio structural heart 6.0). For exact measurements of the internal maximal and minimal diameters (minimal diameter orthogonal to the maximal diameter) of the failed surgical bioprostheses, a multiplanar reconstruction along the exact plane of the valve was performed (Figure 1). Prosthesis implantation of balloon-expandable prostheses was performed under burst rapid ventricular pacing (mostly 180/min) to reduce cardiac output. Closure of transapical access was surgical, whereas percutaneous closure was performed in transarterial procedures with the Perclose Prostar XL or Proglide device.  

The Medtronic CoreValve (Medtronic, Inc) and Edwards Sapien (Edwards Lifesciences) prostheses were utilized.²⁵ In 11 patients, the 23 mm (n=8) or the 26 mm (n=3) Edwards Sapien prosthesis was implanted by transfemoral (n=9) or transapical (n=2) access. In 3 patients, the Medtronic CoreValve prosthesis (26, 29, and 31 mm) was implanted via transfemoral access. 

Outcomes were reported according to the VARC-2 consensus document. ²⁰ Mean follow-up was 234 ± 144 days.

Statistical analysis. Continuous variables are presented as mean ± standard error of the mean (SEM). Categorical variables are given as frequencies and percentages. Kolmogorov-Smirnov test was used to test for normality distribution, while Levene’s test was used to test for homogeneity of variances. Paired or unpaired Student’s t-test was used for comparison of normally distributed continuous variables as appropriate. Categorical variables were tested by the Fisher’s exact test. Correlation between two variables was specified by Pearson’s correlation coefficient. A two-sided P-value of <.05 was established as the level of statistical significance for all tests. All statistical analyses were performed with the use of IBM SPSS version 21 (IBM Corporation).

Results

Baseline characteristics. Transcatheter aortic VIV implantation was performed in 14 patients at the University Hospital Zurich and the Heart Hospital London (University College London). Mean age of the patients was 75 ± 4 years and 43% were male. All patients had failed surgical bioprostheses (Table 1). Primary mode of failure was AS in 50% of patients and AR in 50% (Table 1). Bioprosthesis size did not differ significantly between patients with AS as primary mode of failure compared to those with AR (P=.18). Mean time from SAVR to transcatheter aortic VIV implantation was 8.8 ± 1.3 years. 

Symptoms were congestive heart failure in 13 patients (93%) and angina in 1 patient (7%). Syncope was not reported. The youngest patient was a 32-year old female with Shone’s Complex and severe AR of a degenerated Medtronic Freestyle 21 mm prosthesis due to endocarditis. The predicted operative mortality as assessed by the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was 13.0 ± 2.9%. Severe pulmonary hypertension was observed in 1 patient (7%). Baseline characteristics are summarized in Table 2.

Procedural outcomes, clinical endpoints, and procedure-related complications according to VARC-2 criteria. The prosthesis was successfully implanted in 13 patients (93%). In 1 patient, a second transcatheter valve needed to be implanted due to valve malpositioning too low into the left ventricular outflow tract, resulting in moderate AR, hemodynamic instability, and successful resuscitation during the first attempt. After immediate implantation of a second transcatheter valve, the patient stabilized and no residual AR was observed. None of the procedures were converted into conventional SAVR. Immediate procedural mortality within the first 72 hours after the procedure was 0%. Thirty-day mortality was 7% (1/14); 1 patient died due to respiratory failure 27 days after the procedure. 

Periprocedural or spontaneous myocardial infarction, as well as disabling stroke were not observed at 30 days. Life-threatening or disabling bleeding complications were not seen, and 1 patient had minor bleeding (hematuria). No other known adverse events of TAVI, such as acute kidney injury, vascular access site and access-site related complications, occurred. One patient had new documented atrial fibrillation; new conduction disturbances or new left bundle branch block were not observed. Permanent pacemaker implantation within 30 days was not needed. Consistently, 13/14 patients (93%) were free from complications at 30 days, and the VARC-2 composite endpoint of early safety was met in 1/14 patients (7%). The VARC-2 composite endpoint of clinical efficacy (which includes all-cause mortality, disabling and non-disabling stroke, rehospitalization, New York Heart Association [NYHA] functional class 3 or 4 symptoms, and valve-related dysfunction) was met in 8/14 patients (57%) at 30 days.  

Postprocedural prosthetic valve function. According to VARC-2 standardized definitions, prosthetic valve dysfunction at 30 days was observed in 7/14 patients (50%) due to an increased mean postprocedural transvalvular gradient >20 mm Hg. In patients with AS as primary mode of failure, 6/7 patients (86%) had an increased mean postprocedural transvalvular gradient >20 mm Hg as compared to 1/7 patients (14%) with AR as primary mode of failure (P=.03). Preprocedural transaortic pressure gradients correlated significantly with those after the procedure (r=0.91; P<.001). Of note, at 30-day follow-up, mean transaortic pressure gradients were significantly higher in patients with AS as compared to those with AR as primary mode of failure (36 ± 6 mm Hg vs 16 ± 4 mm Hg; P=.01; n=14) (Figure 2). Mean transaortic pressure gradients were similar in patients treated with Edwards Sapien prosthesis as compared to those treated with Medtronic CoreValve prosthesis at 30-day follow-up. We did not observe any correlation between prosthesis size and postprocedural gradients. At 30-day follow-up, greater than +1 AR was not observed.

Symptomatic improvement. At baseline, 8/14 patients (57%) were in NYHA functional class 3 or 4; at 30-day follow-up, only 1 patient was in NYHA class 3 or 4, representing a clear improvement in symptom status (P=.03) (Figure 3).

Discussion

The present study reports the transcatheter aortic VIV experience of the University Hospital Zurich and the University College London according to VARC-2 standardized endpoint definitions. Transcatheter aortic VIV implantation was safe and effective in this high-risk patient population, and resulted in a significant symptomatic improvement in the vast majority of patients. According to VARC-2 standardized definitions, prosthetic valve dysfunction at 30 days occurred in 50% of the patients. Notably, VARC-2 defined prosthetic valve dysfunction was significantly more frequent in patients with AS rather than AR as primary mode of bioprosthesis failure.

Surgical aortic valve replacement utilizing bioprostheses is frequently performed, in particular in elderly patients, patients with severe comorbidities, or those with increased risk for bleeding events. However, reduced durability of bioprostheses remains a major concern. Indeed, bioprostheses are prone to degenerate within the first or second decade after implantation.^26,27 With the aging population and the increased use of bioprostheses, patients with failed prostheses requiring intervention will become more frequent in the near future, and transcatheter aortic VIV implantation has emerged as a valuable potential treatment alternative to redo open-heart surgery in high-risk individuals.  Several case series have suggested the feasibility and safety of this procedure.^12-16 However, postprocedural prosthesis dysfunction (as defined by VARC-2) remains an important concern.

The VARC standardized endpoint definitions have been proposed in January 2011, in particular for TAVI outcome reporting in clinical trials and registries.¹⁹ The revised VARC-2 endpoint definitions have recently been published.²⁰ Applying the  VARC-2 standardized definitions to the transcatheter aortic VIV patient population, prosthetic valve dysfunction at 30 days was observed in 50% of patients due to an increased mean postprocedural transvalvular gradient >20 mm Hg.  These findings are in line with previous results reporting up to 44% of device dysfunction, mostly secondary to elevated postprocedural transvalvular gradients.^16,28  

In the present study, mean postprocedural transaortic valve gradients were significantly lower in patients treated for bioprosthesis regurgitation as compared to those treated for bioprosthesis stenosis as primary mode of failure. This difference might be due to an increased amount of calcification and pannus or more rigid valvular leaflets in failed stenotic compared to regurgitant aortic bioprostheses. Hence, not only smaller diameters of surgical bioprostheses and thus limited space for device expansion, as suggested in previous studies,¹⁶ but also a primary stenotic mode of bioprosthesis failure may contribute to an increased postprocedural gradient. A thorough preprocedural assessment of the bioprosthesis valve including TEE and MSCT is therefore important in these patients. There are few data available on the comparison of postprocedural gradients in patients treated for different modes of failure, ie, AS versus AR.^17,29 However, as relevant reduction of AR is achieved in most patients,^12,14,16 it has recently been suggested that VIV implantation might be a particularly good treatment option for patients with AR as primary mode of bioprosthesis failure.³⁰ Similarly, in our patient cohort, prosthetic AR greater than or equal to +1 was not observed. Furthermore, our results support this concept, and suggest that patients with AR as primary mode of failure may less frequently have a postprocedural prosthesis dysfunction as defined by VARC-2.   

Study limitations. The small size of our cohorts represents a limitation of this study, and lack of statistical power with regard to correlation analyses cannot be ruled out completely. Further studies examining this question are needed in the near future. Furthermore, studies to assess long-term durability of transcatheter valves in failed surgical bioprostheses are required. Moreover, device design and implantation techniques for this special patient population need to be improved to overcome the current limitations.  

Conclusion

Although we report on a small cohort of patients, transcatheter aortic VIV implantation for failed bioprostheses appears to be a safe and effective strategy to improve symptoms. However, applying the VARC-2 standardized endpoint definitions, postprocedural valve dysfunction was frequently observed, in particular in patients with AS as the primary mode of failure. Larger series of such patients will have to expand and confirm this preliminary experience gained at two centers.

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*Joint first authors.

From the ¹Department of Cardiology, University Heart Center, University Hospital Zürich, Switzerland; ²Department of Cardiology, Heart Hospital, London, United Kingdom; ³Institute of Diagnostic and Interventional Radiology; and ⁴Department of Cardiovascular Surgery, University Heart Center, University Hospital Zürich, Switzerland.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Falk reports grant support from Phillips; speaker fees from Edwards Scientific; consulting fees from Boston Scientific; and DSM board fees from Apica. Dr Landmesser reports lecture and consultation fees from Orbus Neich and St Jude Medical; lecture fees from Terumo Corporation. Dr Mullen reports consulting fees from Edwards LifeSciences. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted September 24, 2013, provisional acceptance given January 13, 2014, final version accepted April 18, 2014.

Address for correspondence: Ulf Landmesser, MD, Department of Cardiology, Cardiovascular Center, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland. Email: ulf.landmesser@usz.ch