Thirty-Day Outcomes in 100 Consecutive Patients Undergoing Transfemoral Aortic Valve Replacement With the Portico Valve on an All-Comer Basis

Abstract: Objectives. Transcatheter heart valves such as the self-expandable Portico valve (St. Jude Medical) are being developed to overcome limitations of first-generation devices. Since clinical experience with this valve is still limited in a real-world setting, we investigated its use on an all-comer basis. Methods. Between October 2015 and October 2016, a total of 100 consecutive patients assessed for transcatheter aortic valve replacement (TAVR) and found suitable for the Portico valve were included. The primary endpoint was 30-day all-cause mortality. Secondary endpoints included immediate postprocedural survival, complications according to Valve Academic Research Consortium (VARC)-2 criteria, and echocardiographic findings. Results. All 100 participants received a Portico valve; the patient group included 56 women (56%) and 44 men (44%) with mean age of 81.7 ± 5.1 years. Mean EuroScore II and STS scores were 6.2 ± 8.6 and 5.2 ± 6.1, respectively. Immediate postprocedural survival rate was 99%. The 30-day mortality rate (6%) was comparable with earlier studies performed in selected patients. Complications included major stroke (2%), minor stroke (2%), major vascular complication (2%), minor vascular complication (4%), cardiac tamponade (1%), major bleeding (3%), conversion into open surgery (1%), and pacemaker implantation (19.5%). Maximal and mean echocardiographic gradients were reduced from 66 mm Hg (range, 21-141 mm Hg) to 15 mm Hg (range, 4-41 mm Hg) (P<.001) and from 44 mm Hg (range, 12-84 mm Hg) to 8 mm Hg (range, 2-25 mm Hg) (P<.001), respectively. A low rate of more-than-mild paravalvular leak was observed (4.4%). Conclusions. Our immediate and 30-day post-TAVR results support favorable survival comparable to other studies, and significant clinical improvement with the Portico valve in non-selected patients in a real-world setting, with short-term complications being uncommon.

J INVASIVE CARDIOL 2017;29(12):431-436.

Key words: aortic valve stenosis, paravalvular leak 

Aortic valve stenosis is the most common valve disease in developed countries¹ and its prevalence increases with age (3.9% between 70-79 years and 9.8% between 80-89 years),² with degenerative impairment being its most common cause.³ Due to its very poor prognosis, particularly after the onset of symptoms (50% mortality at 2 years, 75% mortality at 3 years), and the fact that approximately 40% of patients with this condition are not undergoing surgical aortic valve replacement (SAVR) for several reasons (not referred for SAVR at all, high risk, co-morbidities),⁴ there is a tremendous need for this population to receive appropriate treatment.⁵ Therefore, transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with severe aortic stenosis who are not suitable for SAVR. 

Since the first-in-man percutaneous aortic valve implantation in 2002 by Alain Cribier in Rouen, France,⁶ several first-generation prostheses have been developed. Although initial randomized trials showed similar or even superior results of TAVR vs SAVR^7,8 in both high-risk and intermediate-risk patients, several limitations of these devices are being addressed by newer, second-generation prostheses. Indeed, new device types are being developed in order to overcome complications related to vascular access, risk of stroke, degree of paravalvular leak (PVL), and optimal valve positioning.

The self-expandable Portico valve (St. Jude Medical) is one of the most recent valves on the market. Initial studies with this prosthesis have shown promising results,⁹ but clinical experience is still limited in a real-world setting. 

The aim of this study was to assess the use and performance of this new-generation valve on an all-comer basis, without prior patient selection, provided the annulus size allowed the use of this valve (size <27 mm) and vascular access was available. Baseline data were collected retrospectively and a prospective 30-day follow-up was performed. The study was carried out at the University Hospital of Frankfurt, Division of Cardiology, Frankfurt, Germany.

Methods

Study population. After heart team decision at our center, a total of 100 consecutive patients (October 2015 - October 2016) assessed for TAVR and found suitable for the Portico valve were included. Of note, 43% of patients were included in the ongoing Portico registry (clinicaltrials.gov, identifier, NTC01802788). In addition, over the same period, 35 patients received a Sapien 3 prosthesis (Edwards Lifesciences) and 9 patients received an Evolut R prosthesis (Medtronic) due to annulus size or patient choice. Furthermore, 34 transapical AVRs were also performed within this period of time due to limited femoral vascular access.

Device. The Portico valve is a new-generation device consisting of a self-expandable nitinol frame with three bovine pericardium leaflets and a porcine pericardial sealing cuff.¹⁰ The device can be fully recaptured, retrieved, and repositioned. Furthermore, the large-cell geometry has been designed to ease the access to the coronary ostia.⁹ The position of the Portico prosthesis is annular, as opposed to the supra-annular position of other valves.¹⁰ The Portico valve is available in 23 mm, 25 mm, 27 mm, and 29 mm sizes, covering an annular size range from 19 to 27 mm. The transfemoral delivery system is compatible with 18 Fr (23 and 25 mm valves) and 19 Fr introducer sheaths (27 and 29 mm valves). 

Procedure. All procedures were performed under local anesthesia and, if needed, conscious sedation. Vascular access was obtained by percutaneous arterial puncture and pre-closure was performed using two ProGlide systems (Abbott Vascular) in the femoral artery. Following passage of the native aortic valve, a pre-shaped, Confida guidewire (Medtronic) was placed through a pigtail catheter in the left ventricular cavity for all following steps. An 18 or 19 Fr Ultimum introducer sheath (St. Jude Medical) was used in most cases. Alternatively, a balloon-expandable sheath (Solopath Onset Medical) was used for difficult femoral access due to peripheral artery disease. Per protocol, all patients underwent predilation of the native valve. 

The prosthesis sizes were selected based on previous aortic annulus measurements from transesophageal echocardiography (TEE) and/or computed tomography and calculation of the three-dimensional (3D) perimeter-derived and area-derived annular dimensions using the 3mensio analysis software. The Portico valve was then placed using the dedicated delivery system and re-sheathed if required. Angiography was performed during and after prosthesis deployment to assess position and functionality. Implant depth was measured using the size of the stent frame cells as a reference. Following access closure, complete hemostasis in the groin was documented by digital subtraction angiography (DSA). In case of bleeding, a peripheral balloon was inserted using cross-contralateral femoral access and inflation was maintained until full closure was achieved. Transthoracic echocardiography (TTE) was performed immediately after implantation and before discharge on all patients. 

The antithrombotic regimen used was dual-antiplatelet therapy with aspirin 100 mg once daily and clopidogrel 75 mg once daily for at least 3 months unless there was a need for oral anticoagulation, in which case clopidogrel was added to the oral anticoagulant (new oral anticoagulant or phenprocoumon) for 1 month.

Baseline, periprocedural, and follow-up data. Common baseline and demographic data were collected. TTE was performed in patients before TAVR (between 1 day and 1 month) and after TAVR (at discharge and at 30 days) in order to measure baseline left ventricular ejection fraction (LVEF), aortic valve stenosis and regurgitation degree, left atrium volume and area, aortic valve area, maximal transvalvular gradient (Pmax), and mean transvalvular gradient (Pmean). LVEF was classified based on 2014 American College of Cardiology guidelines (severe dysfunction <30%, moderate dysfunction 30%-39%, mild dysfunction 40%-49%, and normal >50%).

Endpoints. The primary endpoint of the study was all-cause mortality at 30 days. Secondary endpoints included immediate postprocedural survival, complications according to Valve Academic Research Consortium (VARC)-2 criteria,¹¹ New York Heart Association class, and echocardiographic findings. The Ethics Committee of the University Hospital of Frankfurt approved the study protocol and written informed consent was obtained from all patients.

Statistical analysis. All statistical analyses were performed with SPSS statistical software package version 24.0. Descriptive statistics were used with data reported as mean ± standard deviation for normally distributed continuous variables and median (minimum, maximum) used for not normally distributed continuous variables. Frequencies were reported for categorical variables.

As for inferential analysis, Wilcoxon-test was used for non-parametric variables and t-student for parametric ones. For factors predicting mortality, a univariate analysis and a subsequent multivariate analysis were also performed. All significant factors found in the univariate analysis were included in the multivariate analysis using a logistic regression. A further logistic regression was carried out to evaluate factors predicting permanent pacemaker implantation. Statistical significance was set at P<.05. 

Results

Baseline characteristics. A total of 100 consecutive patients with severe aortic stenosis received a Portico valve. Mean age was 81.7 ± 5.1 years and 56% of the patients were women. Mean EuroScore II and STS scores were 6.2 ± 8.6 and 5.2 ± 6.1, respectively. Detailed baseline characteristics of all 100 patients and echocardiographic baseline data are shown in Table 1 and Table 2, respectively.

Procedural results. All patients underwent predilation, most frequently with a Vasc II balloon (90%). The prosthesis was re-sheathed once in 35% of patients, twice in 5% of patients, and exceptionally three times in 2% of patients. Postdilation was carried out in 30% of the implants, where the degree of PVL was considered more than mild. There was a single case of valve-in-valve implantation (Portico 25 mm in a Portico 27 mm). Median implantation depth into the left ventricular outflow tract was 4.5 mm (range, 1-11 mm), with a median left coronary cusp depth of 5.0 mm and a median non-coronary cusp depth of 4.0 mm. Immediate postprocedural survival rate was 99%. There was 1 procedural death (1%) due to ventricular perforation and subsequent cardiac tamponade. Further procedural details are provided in Table 3.

Clinical results. Thirty-day mortality (primary endpoint) was 6%. There were 3 cardiovascular and 3 non-cardiovascular deaths. Besides the mentioned periprocedural death due to ventricular perforation, 1 patient in whom TAVR was used as a last-resort therapy died as a result of a refractory cardiogenic shock. The third cardiovascular death was due to a bradycardial escape rhythm, not improving even after effective temporary pacemaker implantation. As for non-cardiovascular causes of death, 1 patient died from a life-threatening intracerebral bleeding 6 days after the procedure, another patient died on day 15 from a disabling (cardioembolic) stroke, and the third patient’s death was due to urosepsis with acute kidney failure in combination with a hospital-acquired pneumonia. EuroScore II and porcelain aorta before TAVR were factors significantly predicting mortality in univariate analysis; however, multivariate analysis did not reach significance. 

Other complications according to VARC-2 criteria were low (Table 4). The most common complication was pacemaker implantation, followed by vascular complications and stroke. 

Seventeen patients (19.5% of 87 patients without prior pacemaker) received a new pacemaker, most frequently for atrioventricular block III (n = 9). All pacemakers were implanted during the index hospitalization period, and in patients with preexisting conduction abnormalities. Further details on indications for pacemaker implantation and pre-TAVR electrocardiogram in patients receiving a pacemaker are provided in Table 5. Furthermore, based on the overall median implantation depth of 4.5 mm for the whole series, 81.3% of patients who received a pacemaker had a low implantation depth of the prosthesis (ie, >4.5 mm), whereas 18.7% of patients with a new permanent pacemaker implanted showed a high implantation depth (ie, <4.5 mm). However, depth of valve implantation was not a significant predictor for postprocedural permanent pacemaker, and in our cohort, no factor predicting the need for a permanent pacemaker implantation after TAVR could be identified.

A significant improvement of at least one New York Heart Association class at 30 days was found in 82.3% of patients (Figure 1).

Echocardiographic results. Maximal and mean echocardiographic transvalvular gradients were reduced from 66 mm Hg (range, 21-141 mm Hg) to 15 mm Hg (range, 4-41 mm Hg) (P<.001) and from 44 mm Hg (range, 12-84 mm Hg) to 8 mm Hg (range, 2-25 mm Hg) (P<.001), respectively. More-than-mild paravalvular leak was observed in 4.4% of 90 patients at discharge (aortic regurgitation [AR] class 0, 27.7%; AR I, 67.7%; AR II, 3.3%; AR III, 1.1%) and in 4.9% of 61 patients at 30 days (AR class 0, 27.9%; AR I, 65.6%; AR II, 4.9%; AR III, 1.6%) (Figure 2). Median LVEF showed a significant improvement (from 55% [range, 15%-75%] to 60% [range, 20%-70%]; P<.05), and 11.7% of patients showed at least a one-level improvement in their LVEF category. 

Discussion

Initial studies for a new valve prosthesis usually include selected patients, and the outcome may not be fully representative of a real-world setting.¹² Our all-comer study included all consecutive patients assessed for TAVR, and could reflect more accurately the current practice in a tertiary hospital. Large multicenter studies, such as PARTNER 2 (Edwards Lifesciences valves) or the CoreValve US Pivotal trial (Medtronic CoreValve) included patients selected according to an exact set of inclusion and exclusion criteria (eg, the PARTNER 2 study⁸ excluded patients with prior myocardial infarction <30 days, previous aortic regurgitation, a complex coronary disease, or creatinine >3 mg/dL). The recent trend to expand TAVR indications beyond high-risk patients to include intermediate-risk candidates is reflected in the slightly lower risk scores (STS and EuroScore II) observed in our cohort compared to previous studies. 

We report the results of 100 consecutive patients with severe aortic stenosis not suitable for SAVR who received the new-generation recapturable and repositionable self-expanding Portico bioprosthesis. To our knowledge, this is one of the largest real-world series published with this kind of valve. The valve was implanted on an all-comer basis in unselected patients undergoing TAVR. The only reasons for not receiving a Portico valve were annulus size or the patient’s specific choice for another type of valve. 

Previous studies, such as the first-in-human experience with the Portico valve¹³ and a multicenter clinical study,¹⁴ already showed excellent results. In spite of using an all-comers approach, 30-day mortality in our cohort was 6%, which is not substantially higher than mortality in previous studies in selected patients.^12-14 Compared to other new-generation valves such as Lotus (6.4%),¹⁵ our cohort had a similar 30-day mortality rate.

Although not shown to affect mortality, the need for a pacemaker after TAVR is still an important issue in transcatheter valves. In our cohort, the rate of new pacemaker implantation was 19.5%; however, when compared to the rates reported for two other second-generation self-expandable valves, this rate was lower than those reported in similar studies using the Lotus valve (36.5%) and comparable to those observed in a cohort using the Evolut R valve (20.7%).¹⁵ Balloon-expandable valves have typically shown lower rates of pacemaker implantation in previous studies, although similarly high rates (18.4 %) have occasionally been reported for some cohorts using Sapien 3 valves.¹⁶ Previous smaller series with the Portico valve have shown similar or lower pacemaker implantation rates.^12,14,17 Further studies are needed to identify factors predicting the need for pacemaker implantation with this newly developed valve model.   

As described in a previous review,¹⁸ the most common indication for pacemaker implantation after TAVR in our cohort was atrioventricular block III. Newly appearing conduction disturbances are well known after TAVR, and all patients should be monitored for at least 3 days after implantation.¹¹ In a detailed analysis of baseline (preprocedural) electrocardiograms of the patients receiving post-TAVR pacemaker implantation, some degree of conduction abnormality could be found in nearly all of these patients. The most common abnormalities were atrial fibrillation, atrioventricular block I, and left anterior fascicular block, followed by right bundle-branch block and left bundle-branch block. Such findings support the results of a previous analysis of predictive factors for pacemaker implantation in a study by Gonska et al, suggesting that first-degree atrioventricular block and right bundle-branch block are two of the most relevant conduction abnormalities associated with pacemaker implantation.¹⁶ Furthermore, about 82% of patients who received a pacemaker in our series had a low depth of implantation of the valve (>4.5 mm). Such findings suggest that depth of implantation could be a potential predictor for pacemaker implantation when using a Portico valve. Nevertheless, this is a controversial subject with many conflicting observations, and larger prospective studies are warranted.¹⁸ 

The need for correction through valve-in-valve was rare. In our study cohort, only 1 out of 100 patients required a corrective procedure by valve-in-valve, whereas valve-in-valve procedures were needed in 1 out of 10 patients in a study by Willson et al¹³ in 4 out of 102 patients in a study by Manoharan et al,¹⁴ and in 4 out of 57 patients in a study by Perlman et al.¹² Overall, the degree of more-than-mild PVL was reasonable (4.4%) and similar to other Portico series (3.6%-10%).^12-14 

In contrast to previous studies with Portico valves in which large-sized valves were unavailable or scarcely used, 45% of our implanted valves were 29 mm. In the Perlman study, 7% of valves were 29 mm.¹² The present study is one of the first to show success with a 29 mm valve. Since this is an all-comer study, this finding might suggest that patients in a real-world setting tend to have larger aortic valve annuli. The Portico valve is not a good option for patients with an extremely large annulus (ie, >27 mm). Therefore, larger valve sizes should be developed in the near future to cover this group of patients.

Implantation of the Portico valve proved to be safe and feasible, with good outcomes at short-term follow-up. The further large-scale use of this valve needs to be assessed in randomized trials compared with other new-generation self-expanding and balloon-expandable valves. One study has already compared the Portico valve with the balloon-expandable Sapien XT valve in patients with small aortic annuli, with similar short-term results.¹⁹

Despite being one of the largest series with this valve, the low number of events in our population is most likely the reason that multivariate analysis of factors predicting mortality and other complications, such as pacemaker implantation, did not achieve statistical significance. 

Study limitations. Despite the limitation of a retrospective baseline data collection, bias seems unlikely because all patients were managed according to the same institutional protocol. Selection bias was also unlikely because consecutive patients were included. Furthermore, follow-up outcomes were recorded prospectively. 

No patients with extremely small annuli were included; thus, the 23 mm size valve was not used and cannot be assessed based on our results. As previously stated, the present all-comers population included a high number of patients needing large-sized valves.

Conclusion

The Portico valve shows excellent short-term results when used on an all-comer basis, comparable to previous studies in selected patients and also to those shown with other valves regarding major complications and particularly PVL, which has been shown to have prognostic value. Further studies with a longer follow-up period are needed to evaluate the long-term results of the Portico valve in a real-world setting and to compare it with other new-generation aortic prostheses.

References

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16.     Gonska B, Seeger J, Keßler M, von Keil A, Rottbauer W, Wöhrle J. Predictors for permanent pacemaker implantation in patients undergoing transfemoral aortic valve implantation with the Edwards Sapien 3 valve. Clin Res Cardiol. 2017;106:590-597. Epub 2017 Mar 10.

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19.     Del Trigo M, Dahou A, Webb JG, et al. Self-expanding Portico valve versus balloon-expandable Sapien XT valve in patients with small aortic annuli: comparison of hemodynamic performance. Rev Esp Cardiol (Engl Ed). 2016;69:501-508.

*Joint first authors.

From the ¹Department of Cardiology, University Hospital Frankfurt, Goethe University, Germany; and the ²Department of Cardiothoracic Surgery, University Hospital Frankfurt, Goethe University, Germany. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Vasa-Nicotera is a proctor for St. Jude Medical/Abbott Vascular. Dr Fichtlscherer is a proctor for St. Jude Medical/Abbott Vascular and Edwards Lifesciences. The remaining authors report no conflicts of interest regarding the content herein. 

Manuscript submitted August 23, 2017 and accepted September 1, 2017.

Address for correspondence: Silvia Mas-Peiro, MD, MSc, Department of Cardiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main,  Germany. Email: silviamaspeiro@gmail.com