Author + information
- Received April 30, 2015
- Revision received July 14, 2015
- Accepted July 30, 2015
- Published online October 1, 2015.
- Klaudija Bijuklic, MD∗,
- Timo Haselbach, MD†,
- Julian Witt, MD‡,
- Korff Krause, MD‡,
- Lorenz Hansen, MD†,
- Ralf Gehrckens, MD§,
- Friedrich-Christian Rieß, MD, PhD† and
- Joachim Schofer, MD, PhD∗,‖∗ ()
- ∗Medical Care Center Prof. Mathey, Prof. Schofer, Hamburg, Germany
- †Department of Cardiac Surgery, Albertinen Heart Center, Hamburg, Germany
- ‡Department of Cardiology, Albertinen Heart Center, Hamburg, Germany
- §Department of Radiology, Albertinen Hospital, Hamburg, Germany
- ‖Department for Percutaneous Treatment of Structural Heart Disease, Albertinen Heart Center, Hamburg, Germany
- ↵∗Reprint requests and correspondence:
Prof. Dr. med. Joachim Schofer, Medical Care Center, Albertinen Heart Center, Wördemannsweg 25-27, 22527 Hamburg, Germany.
Objectives The purpose of this study was to analyze the effect of transcatheter aortic valve replacement (TAVR) without versus with prior balloon aortic valvuloplasty (BAV) on the risk of cerebral embolization in patients who receive a balloon-expandable valve.
Background Avoiding BAV prior to TAVR may simplify the procedure, but the risk of cerebral embolization is currently unknown.
Methods A total of 87 consecutive high surgical-risk patients with no contraindications for diffusion-weighted magnetic resonance imaging (DW-MRI) were enrolled. Thirty-two patients received a balloon-expandable aortic valve with and 55 patients without BAV. The incidence, number, and volume of new ischemic lesions in DW-MRI performed 2 to 7 days after TAVI were evaluated.
Results Mean age (83.8 ± 5.2 years vs. 82.9 ± 6.8 years) and sex (43.8% vs. 52.7% male) of the patients with versus without BAV, respectively, as well as other demographic and hemodynamic data were not significantly different between both groups. The procedural success rate was 93.5% with and 98.2% without BAV, and procedure duration and contrast volume were significantly lower without BAV. The incidence of new cerebral ischemic lesions in the total cohort was 66.7%. Compared with patients with BAV, those without BAV had a significantly higher total volume of cerebral ischemic lesions (235.4 ± 331.4 mm3 vs. 89.5 ± 128.2 mm3; p = 0.01).
Conclusions The implantation of a balloon-expandable aortic valve without versus with prior BAV, although performed with a shorter procedure time and lower contrast volume, is associated with a significantly higher volume of cerebral ischemic lesions.
Balloon aortic valvuloplasty (BAV) prior to transcatheter aortic valve replacement (TAVR) is believed to be a necessary step for the implantation of a balloon-expandable prosthesis.
BAV, however, may be associated with several adverse events. It needs rapid pacing, which, in the presence of poor left ventricular function, may increase the risk of the procedure; it may be associated with aortic rupture; and it may be in part responsible for cerebral embolization with the risk of stroke (1). Avoiding BAV may simplify the procedure, but the risk of cerebral embolization is currently unknown. For a self-expandable device, TAVR without BAV has been shown to be feasible, and the authors speculated that this approach may reduce the incidence of stroke (2).
The aim of the present study was to analyze the effect of implanting a balloon-expandable valve without prior BAV on cerebral embolization compared with patients who received the balloon-expandable valve after BAV.
Consecutive patients who met the inclusion/exclusion criteria were enrolled in the present study. Inclusion criteria were the presence of symptomatic severe aortic stenosis, age >75 years, and a high surgical risk as determined by an interdisciplinary heart team.
Exclusion criteria were pacemaker, claustrophobia, refusal of diffusion-weighted magnetic resonance imaging (DW-MRI), a history of a stroke or transient ischemic attack (TIA) within the prior 6 months, renal failure (estimated glomerular filtration rate <30 ml/min, calculated from serum creatinine by the Cockcroft-Gault formula), presentation with cardiogenic shock or severe hypotension (systolic blood pressure <90 mm Hg), undergoing any other cardiac surgical or interventional procedure (e.g., concurrent coronary revascularization) during or after the TAVR procedure before DW-MRI, and experiencing a clinical apparent stroke within 3 days after TAVR.
The patients underwent a standard screening procedure including echocardiography and multislice computed tomography. Aortic annulus size was measured by multislice computed tomography and transesophageal echocardiography (TEE) and aortic effective orifice valve area by TEE.
Patients were either on dual antiplatelet therapy (aspirin 100 mg plus clopidogrel 75 mg/day) before TAVR or received a loading dose of aspirin 500 mg intravenously and clopidogrel 600 mg orally on the day of the procedure. Dual antiplatelet therapy was recommended for 6 months. Patients on oral anticoagulation therapy received a clopidogrel loading dose followed by 75 mg/day for 6 months. The TAVR procedure was performed either under general anesthesia or conscious sedation. For BAV, a dedicated Edwards SAPIEN valvuloplasty balloon catheter (Edwards Lifesciences, Irvine, California) was used. All patients received heparin to increase the activated clotting time >250 s.
Diffusion-weighted magnetic resonance imaging
Cerebral DW-MRI was performed 2 to 7 days after TAVR using a 1.5-T machine (Magnetom Sonata, Siemens, Erlangen, Germany). Echo planar imaging with the following parameters was used: repetition time 3,000 ms; echo time 84 ms; 19 slices with a slice thickness of 6 mm; field of view 230 mm; diffusion values b = 0, 500, and 1,000 s/mm2; fat saturation; and time of acquisition 71 s. Additionally, apparent diffusion coefficient maps were obtained. A new lesion was defined as a focal hyperintense area detected by the fluid-attenuated inversion recovery sequence, corresponding to a restricted diffusion signal in the diffusion-weighted imaging sequence, and confirmed by apparent diffusion coefficient mapping to rule out a shine-through artefact. Two independent physicians (T.H., R.G.) analyzed the DW-MRI for new ischemic lesions. The incidence, number, and volume of new ischemic lesions in DW-MRI were evaluated by physicians unaware of the patients’ treatment. Interobserver agreement revealed a kappa of 0.75 (p < 0.001).
According to the Valve Academic Research Consortium-2 criteria (3), technical success was defined as successful vascular access, deployment of the device and retrieval of the delivery system, and correct position of the device in the proper anatomical location with adequate performance of the prosthetic heart valve and without use of multiple prostheses.
Major adverse cardiac and cerebrovascular events (MACCE) were defined as death, myocardial infarction, and stroke.
Stroke was defined as new prolonged (>24 h) or persistent neurological deficit.
Continuous data were presented as mean ± SD and compared with the unpaired t test or Mann-Whitney U test as appropriate. Categorical data were presented as count (percentages) and compared with the chi-square test. A p < 0.05 was considered statistical significant. Interobserver variability was evaluated by kappa statistics. Statistical analysis was performed using GraphPad Prism version 6.0. (GraphPad Software, San Diego, California) and SPSS software (version 20.0, SPSS Inc., Chicago, Illinois).
A total of 87 patients were included in the study. In 32 patients, TAVR was performed with prior BAV, and in 55 patients, TAVR was performed without BAV. All patients who received an Edwards SAPIEN XT valve (n = 19) routinely had BAV before valve implantation. After the availability of the Edwards SAPIEN 3 valve, only in case of a severe asymmetric valve calcification or a planimetric aortic valve effective orifice area ≤0.5—as measured by intraprocedural TEE—was a valvuloplasty performed (n = 13). All other patients receiving an Edwards SAPIEN 3 valve were treated without BAV (n = 55).
Within 3 days following TAVR, 4 patients (3 patients without, 1 patient with BAV) experienced a stroke and were excluded from the study.
The patient demographics are summarized in Table 1. There were no differences between patients with versus without BAV in terms of age, sex, and comorbidities. Also transvalvular aortic gradient, effective aortic orifice area, aortic annulus size, as well as left ventricular function were not statistically different (Table 2).
The procedural results are summarized in Table 3. The procedural success rate was 93.5% in the patients with and 98.2% in patients without BAV driven by a difference in moderate aortic insufficiency post TAVR. The rate of paravalvular leaks was not different between both groups. Post-dilation was performed in 3 patients without BAV and in 1 patient with BAV due to moderate aortic regurgitation. Patients without BAV had a significantly shorter procedure duration and contrast volume.
The 30-day MACCE rate was 0%. Major vascular complications according to the Valve Academic Research Consortium-2 criteria were found in 3.4% (n = 3) of patients. All 3 patients had major access site–related bleeding requiring surgical intervention. Nine patients (10.3%) needed a covered stent implantation due to access site–related perforation or dissection. There were no differences in vascular complications between the 2 groups.
DW-MRI was performed 4.8 ± 2.4 days after TAVR. The timing of DW-MRI was significantly different, at 4.3 ± 2.5 days post-intervention in the BAV group compared with 5.1 ± 2.4 days in patients without BAV (p = 0.03).
The results of the cerebral DW-MRI are summarized in Figure 1.
The incidence of new ischemic cerebral lesions in the total cohort was 66.7% (n = 58). In patients with lesions, they were located bilaterally in 43.1% (n = 25), in the right hemisphere in 24.1% (n = 14) and in the left hemisphere in 32.8% (n = 19). Compared with patients with BAV, those without BAV had a significantly higher total volume of cerebral ischemic lesions and a numerically higher incidence and number of ischemic lesions, which, however, was not statistically significant.
The main findings of the present study are that implantation of a balloon-expandable valve without prior BAV is associated with a high procedural success rate and, compared to TAVR with BAV, with a significantly shorter procedure duration and contrast volume but with a higher cerebral embolic burden.
Balloon valvuloplasty before implantation of a percutaneous aortic valve is widely used to facilitate the crossing of the calcified aortic valve. So far, few studies have investigated the clinical value of avoiding dilation of the stenotic valve before TAVR (2,4). In a pilot study comprising 60 consecutive patients, who received the self-expandable CoreValve (Medtronic, Minneapolis, Minnesota) without pre-dilation, Grube et al. (2) found a feasibility and safety of TAVR similar to the standard approach with pre-dilation. Post-dilation, however, known to be an independent risk factor for stroke, had to be performed in 16.7% of the patients.
Other small studies demonstrated the feasibility of the transfemoral implantation of the Edwards SAPIEN XT valve without prior BAV (5,6). The authors of the previously mentioned papers speculated that avoiding pre-dilation may reduce the risk of stroke. However, the effect of this strategy on the rate of cerebral embolization has not been investigated so far.
Compared with the Edwards SAPIEN XT, the delivery system of the Edwards SAPIEN 3 aortic valve prosthesis has a lower profile and a steerable and supportive delivery catheter, all of which may facilitate a direct valve implantation. We assumed that using a less bulky TAVR device with a simplified implantation technique (by avoiding pre-dilation) may exert beneficial effects on the periprocedural rate of cerebral embolization.
Indeed, in the present study TAVR without BAV compared with TAVR with BAV was feasible and led to a significantly shorter procedure duration and contrast volume. This is consistent with data from Möllmann et al. (5), who in a retrospective study, found lower volume of contrast dye and a trend for a shorter procedure duration in 26 patients receiving an Edwards SAPIEN XT valve without versus 30 patients with pre-dilation.
The MACCE rate in the present study was 0%, without any death, stroke, or myocardial infarction at 30 days. This excellent result may in part be explained by the exclusion of patients in unstable condition from the study according to the inclusion/exclusion criteria. Of note, however, there was no difference in the rate of stroke between patients with compared with patients without pre-dilation, who could not be included in the study.
TAVR and cerebral ischemic lesions
DW-MRI allows detection and localization of cerebral ischemic lesions which are found in 74% to 100% of patients after TAVR (7–9). Patients with ischemic lesions have a 3-fold risk of stroke (10). Although in most instances, these lesions are not associated with apparent neurological symptoms, there is a growing body of evidence linking silent ischemic lesions to dementia and decline in cognitive function (11,12).
In the randomized CLEAN-TAVI (CLaret Embolic Protection ANd TAVI- Trial) study, the use of a cerebral protection device in patients undergoing TAVR significantly reduced the number of DW-MRI cerebral ischemic lesions, which was associated with improved short-term neurological outcome (15). The results of the recently published randomized DEFLECT III (A Prospective, Randomized Evaluation of the TriGuard™ HDH Embolic Deflection Device During TAVI) trial (16) are pointing in the same direction. A reduction of ischemic brain volume under neuroprotection was associated with improvement in short-term and delayed memory.
In spite of this data, the higher cerebral ischemic burden found in patients undergoing TAVR without pre-dilation in the present study is of concern. The reason for this finding remains speculative.
In the present study, we had a significant difference in timing of DW-MRI after TAVR (0.8 day) between the 2 groups, which could affect the results. Also others used a time range between 2 and 7 days for DW-MRI (9,16). In the CLEAN TAVI trial (15), serial DW-MRIs were performed at days 2 and 7, revealing a numerical decrease in the number and volume of lesions at day 7 compared with day 2. In the PROTAVI-C pilot study (Prospective Randomized Outcome study in patients undergoing TAVI to Examine Cerebral Ischemia and Bleeding Complications) (9), by 30 days after TAVR all new lesions had disappeared. Based on these findings, later cardiac magnetic resonance imaging could have missed some new lesions. However, in the present study, it was the group of patients with a higher lesion volume (TAVR without BAV) which was studied 0.8 day later; thus, a disappearance of pre-existing lesions cannot explain the difference.
From primary stenting of coronary lesions, it is known that pre-dilation is associated with at least a trend for less myocardial injury (17). It can be speculated that pre-dilation leads to plaque fragmentation, which can reduce the risk of embolization and the size of pieces that embolize during stent implantation. Our findings are in support with this assumption. The main difference between the 2 groups was the volume of ischemic brain, which was significantly higher in patients without pre-dilation, whereas the incidence and the number of lesions were not significantly different.
The present study is the first to provide insights into the risk of cerebral embolization when omitting BAV prior to balloon-expandable aortic valve implantation. It remains to be shown whether this translates into a higher stroke rate. Even if not, cerebral ischemic lesions potentially deteriorate neurocognitive function and should therefore be avoided. Cerebral embolic protection devices may be of specific value for TAVR without BAV using a balloon-expandable valve.
This is a single-center, nonrandomized study with a small number of patients, and therefore needs to be confirmed in a larger randomized patient population. Patients undergoing Edwards SAPIEN 3 without BAV were compared with a historical control group of patients who received either an Edwards SAPIEN XT or an Edwards SAPIEN 3 aortic valve with BAV. Even with the use of the higher-profile and less-flexible SAPIEN XT device in the group with BAV, the difference in ischemic lesion volume was highly significant emphasizing the role of pre-dilation to reduce the risk of cerebral embolization.
The implantation of a balloon-expandable aortic valve without prior BAV is associated with a significantly shorter procedure duration and lower contrast volume than implantation with prior BAV. A significant higher volume of cerebral ischemic lesions after TAVI without BAV, however, is of concern and needs to be addressed by further studies.
WHAT IS KNOWN? In the majority of patients, mostly silent cerebral ischemic lesions are present after TAVR. There is evidence that silent ischemic lesions are linked to dementia and decline in cognitive function at long term. Omitting BAV before aortic valve implantation may simplify the procedure and may affect cerebral embolization.
WHAT IS NEW? Implantation of a balloon-expandable valve without prior BAV was associated with a significantly shorter procedure duration and lower contrast volume, but with a significantly higher volume of cerebral ischemic lesions.
WHAT IS NEXT? This finding has to be proven in a randomized trial.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- balloon valvuloplasty
- diffusion-weighted magnetic resonance imaging
- transcatheter aortic valve replacement
- Received April 30, 2015.
- Revision received July 14, 2015.
- Accepted July 30, 2015.
- 2015 American College of Cardiology Foundation
- Grube E.,
- Naber C.,
- Abizaid A.,
- et al.
- Möllmann H.,
- Kim W.K.,
- Kempfert J.,
- et al.
- Conradi L.,
- Schaefer A.,
- Seiffert M.,
- et al.
- Ghanem A.,
- Müller A.,
- Nähle C.P.,
- et al.
- Kahlert P.,
- Knipp S.C.,
- Schlamann M.,
- et al.
- Rodés-Cabau J.,
- Kahlert P.,
- Neumann F.J.,
- et al.
- Barber P.A.,
- Hach S.,
- Tippett L.J.,
- Ross L.,
- Merry A.F.,
- Milsom P.
- Restrepo L.,
- Wityk R.J.,
- Grega M.A.,
- et al.
- ↵Linke A, Haussig, S, Dwyer, MG, et al. CLEAN-TAVI: a prospective, randomized trial of cerebral embolic protection in high-risk patients with aortic stenosis undergoing transcatheter aortic valve replacement. Paper presented at: TCT 2014; September 13-17, 2014; Washington, DC.
- Mehilli J.,
- Kastrati A.,
- Dirschinger J.,
- et al.