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Clinical outcomes following transcatheter aortic valve implantation in patients with porcelain aorta

Open AccessPublished:October 28, 2021DOI:https://doi.org/10.1016/j.jcct.2021.10.006

      Abstract

      Background

      Current guidelines favor transcatheter aortic valve implantation (TAVI) over surgical aortic valve replacement in patients with porcelain aorta (PAo). The clinical relevance of PAo in patients undergoing TAVI is however incompletely understood. The purpose of this study is to evaluate clinical outcome of patients with PAo undergoing TAVI.

      Methods

      Consecutive patients undergoing TAVI were enrolled in a prospective single-center registry. Presence of PAo was evaluated by ECG-gated multi-slice computed tomography prior to the intervention. The primary endpoint was disabling stroke.

      Results

      Among 2199 patients (mean age, 82.0 ​± ​6.3 years; 1135 females [51.6%]) undergoing TAVI between August 2007 and December 2019, 114 patients (5.2%) met VARC-2 criteria for PAo. Compared to individuals without PAo, patients with PAo were younger (79.4 ​± ​7.4 years vs. 82.1 ​± ​6.2 years; p ​< ​0.001), had a lower left ventricular ejection fraction (51.8 ​± ​14.9% vs. 55.3 ​± ​14.2%; p ​= ​0.009) and higher STS-PROM Scores (6.5 ​± ​4.3% vs. 4.9 ​± ​3.4%; p ​< ​0.001). At 1 year, disabling stroke occurred more often in patients with PAo (7.2%) than in those without (3.0%) (HRadj, 2.49; 95% CI, 1.12–5.55). The risk difference emerged within 30 days after TAVI (HRadj, 3.70; 95% CI, 1.52–9.03), and was driven by a high PAo-associated risk of disabling stroke in patients with alternative access (HRadj, 5.79; 95% CI, 1.38–24.3), not in those with transfemoral (HRadj, 1.47; 95% CI 0.45–4.85).

      Conclusions

      TAVI patients with PAo had a more than three-fold increased risk of periprocedural disabling stroke compared to patients with no PAo. The difference was driven by a higher risk of stroke in patients treated by alternative access.

      Graphical abstract

      Keywords

      Abbreviation and acronyms

      AS
      aortic stenosis
      ECG
      electrocardiogram
      MACCE
      major adverse cardiac and cerebrovascular events
      MSCT
      multi-slice computed tomography
      PAo
      Porcelain aorta
      SAVR
      surgical aortic valve replacement
      STS-PROM
      Society of Thoracic Surgeons-Predicted Risk of Mortality
      TAVI
      transcatheter aortic valve implantation
      TCEP
      transcatheter cerebral embolic protection
      VARC
      Valve Academic Research Consortium

      1. Introduction

      Presence of porcelain aorta (PAo), defined as circumferential calcium deposition in the ascending aorta,
      • Kappetein A.P.
      • Head S.J.
      • Généreux P.
      • et al.
      Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document.
      is considered a relative contraindication for surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS).
      • Carrel T.
      Should the porcelain aorta be revisited in the era of transcatheter aortic valve replacement?.
      Transcatheter aortic valve implantation (TAVI) prevents the need for aortic cross-clamping and demonstrated feasible in patients with PAo.
      • Useini D.
      • Haldenwang P.
      • Schlömicher M.
      • et al.
      Mid-term outcomes after transapical and transfemoral transcatheter aortic valve implantation for aortic stenosis and porcelain aorta with a systematic review of transfemoral versus transapical approach.
      • Ramirez-Del Val F.
      • Hirji S.A.
      • Yammine M.
      • et al.
      Effectiveness and safety of transcatheter aortic valve implantation for aortic stenosis in patients with "porcelain" aorta.
      • Zahn R.
      • Schiele R.
      • Gerckens U.
      • et al.
      Transcatheter aortic valve implantation in patients with "porcelain" aorta (from a Multicenter Real World Registry).
      Consequently, current European and American guidelines on valvular heart disease favor TAVI over SAVR in the presence of PAo.
      • Otto C.M.
      • Nishimura R.A.
      • et al.
      Writing Committee Members
      ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American heart association Joint committee on clinical Practice guidelines.
      ,
      • Baumgartner H.
      • Falk V.
      • Bax J.J.
      • et al.
      ESC/EACTS Guidelines for the management of valvular heart disease.
      However, available evidence of TAVI in patients with PAo is limited to cohorts modest in size, and anatomical determinants of clinical outcome are underappreciated in currently used risk scores.
      • Thourani V.H.
      • Suri R.M.
      • Gunter R.L.
      • et al.
      Contemporary real-world outcomes of surgical aortic valve replacement in 141,905 low-risk, intermediate-risk, and high-risk patients.
      Introduction of the transcatheter delivery system by retrograde approach interferes with PAo and may influence periprocedural outcomes. An antegrade, transapical approach foregoes crossing of the aortic arch with large-bore catheters, but comes at the expense of thoracotomy.
      The aim of the present study was therefore to investigate the impact of PAo on rates of disabling stroke in patients undergoing TAVI.

      2. Methods

      2.1 Study design and patient population

      Consecutive patients undergoing TAVI at Bern University Hospital, Switzerland between August 2007 and December 2019 were prospectively enrolled into an institutional registry, which is a part of the Swiss TAVI registry (NCT01368250). The registry was approved by the local ethics committee and complied with the Declaration of Helsinki. Written informed consent for the intervention and the prospective follow-up was obtained from all subjects. Patients were eligible for the present analysis if they underwent electrocardiogram (ECG)-gated multi-slice computed tomography (MSCT) prior to the intervention. Patients not undergoing MSCT or with MSCT with poor image quality of the aortic window were excluded from the present analysis.
      Decision for TAVI, prosthesis type, and size was made by consensus in a dedicated Heart Team, consisting of cardiac surgeons, interventional cardiologists, and cardiac imaging specialists. Default access route was transfemoral, but in patients with unfavorable vascular anatomy, alternative approaches were considered, including the transapical, subclavian, carotid, and transcaval access route. Post-procedural care included continuous rhythm monitoring, daily 12-lead ECG, and transthoracic echocardiography. Clinical follow-up was assessed at 30 days and one year after TAVI by standardized telephone interviews, documentation from referring physicians, and hospital discharge records. All adverse events were independently adjudicated by the local clinical events committee, according to the Valve Academic Research Consortium-2 (VARC-2) criteria.
      • Kappetein A.P.
      • Head S.J.
      • Généreux P.
      • et al.
      Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document.
      Patients with PAo were compared to those without PAo with regards to the prespecified primary endpoint disabling stroke. Secondary endpoints included all-cause and cardiovascular mortality, a composite of major adverse cardiac and cerebrovascular events (MACCE), life-threatening bleeding events, and major access site complications.

      2.2 Multi-slice computed tomography image acquisition and analysis

      MSCT was performed as previously described,
      • Okuno T.
      • Asami M.
      • Khan F.
      • et al.
      Does isolated mitral annular calcification in the absence of mitral valve disease affect clinical outcomes after transcatheter aortic valve replacement?.
      using either a Siemens Somatom Sensation Cardiac 64 scanner with a slice collimation of 64 ​× ​0.75 ​mm (Siemens Healthcare, Erlangen, Germany) or a Siemens Somatom Definition Flash Dual-Source scanner (Siemens Healthcare, Erlangen, Germany). In brief, MSCT was conducted with a collimation of 128 ​× ​0.6 ​mm, a gantry rotation time of 280–370 ​ms, a tube voltage of 100 or 120 ​kV, and tube current according to patient size (Siemens Medical Solutions, Inc., Forchheim, Germany). All CT images were transmitted to a dedicated software customized for valve analysis (3mensio Valves, version 9.0, 3mensio Medical Imaging BV, Bilthoven, the Netherlands) and were blindly assessed by a board-certificated cardiologist. If available, a systolic phase was selected to assess the aortic valve dimension. Validated methodology was used to quantify the calcium volume in the aortic valvar complex and left ventricular outflow tract by contrast scan (850-Hounsfield unit threshold).
      • Jilaihawi H.
      • Makkar R.R.
      • Kashif M.
      • et al.
      A revised methodology for aortic-valvar complex calcium quantification for transcatheter aortic valve implantation.
      PAo was defined according to the VARC-2 criteria as presence of severe atheromatous plaques or heavy circumferential calcification of the ascending aorta extending to the aortic arch,1 as assessed by non-contrast axial CT (Fig. 1).
      Fig. 1
      Fig. 1Multi-slice native computed tomography images of porcelain aorta.
      (A) Axial MPR, (B) coronal MPR, (C) MIP at LAO 45°, (D) Volume rendering. MIP ​= ​maximal intensity projection, MPR ​= ​multiplanar reformation.

      2.3 Statistical analysis

      Statistical analyses were performed using Stata 16.1 (StataCorp, College Station, TX, USA).
      Means and standard deviation are provided to describe continuous variables, while frequencies and percentages are provided for categorical variables. T-tests were used to compare means of continuous variables between groups. Categorical variables were analyzed using Chi-Square-test. Kaplan Meier estimators comparing PAo vs. no PAo were applied to analyze time-to-event data. Hazard ratios (HR) and 95% confidence intervals (CI) are from Cox regression models, crude and also adjusted for age, history of stroke or transit ischemic attack, New York Heart Association classification III or IV, peripheral artery disease, arterial hypertension, left ventricular ejection fraction, STS-PROM score, and femoral access. The two-tailed significance level was set at α ​< ​0.05.

      3. Results

      3.1 Baseline characteristics

      Among 2641 consecutive patients who underwent TAVI between August 2007 and December 2019, 2199 patients underwent MSCT and were considered for the present analysis. PAo according to VARC-2 criteria was documented in 114 individuals (5.2%). Demographic and clinical characteristics of the study participants are presented in Table 1. Patients with PAo were younger than patients with no PAo (79.4 ​± ​7.4 years vs. 82.1 ​± ​6.2 years; p ​< ​0.001), and had higher STS-PROM scores (6.5 ​± ​4.3 vs. 4.9 ​± ​3.4; p ​< ​0.001). Patients with PAo had lower left ventricular ejection fraction than patients without PAo (51.8 ​± ​14.9% vs. 55.3 ​± ​14.2%; p ​= ​0.009), while transvalvular gradients were comparable between groups.
      Table 1Baseline characteristics.
      OverallNo-porcelain AortaPorcelain Aortap Value
      N ​= ​2199N ​= ​2085N ​= ​114
      Age (years)82.0 ​± ​6.382.1 ​± ​6.279.4 ​± ​7.4<0.001
      Female gender, n (%)1135 (51.6)1081 (51.8)54 (47.4)0.39
      Body mass index (kg/m2)26.6 ​± ​5.326.6 ​± ​5.226.4 ​± ​5.70.59
      NYHA classification III or IV, n (%)1501 (68.4)1417 (68.1)84 (73.7)0.26
      Past medical history
       Diabetes mellitus, n (%)554 (25.2)514 (24.7)40 (35.1)0.02
       Hypercholesterolaemia, n (%)1454 (66.2)1367 (65.6)87 (77.0)0.01
       History of arterial hypertension, n (%)1839 (86.1)1797 (86.2)96 (84.2)0.58
       History of coronary artery disease, n (%)1317 (59.9)1229 (58.9)88 (77.2)<0.001
       Previous stroke or TIA, n (%)251 (11.4)232 (11.1)19 (16.7)0.09
       Peripheral vascular disease, n (%)293 (13.3)257 (12.3)36 (31.6)<0.001
       Chronic obstructive pulmonary disease, n (%)266 (12.1)235 (11.3)31 (27.4)<0.001
       Renal failure (eGFR <60 ​mL/min/1.73m2), n (%)1440 (65.6)1371 (65.9)69 (60.5)0.27
       Permanent pacemaker, n (%)185 (8.4)171 (8.2)14 (12.3)0.16
       History of atrial fibrillation, n (%)1470 (66.8)1403 (67.3)67 (58.8)0.07
      Risk assessment
       Logistic EuroSCORE (%)15.3 ​± ​13.214.8 ​± ​12.923.5 ​± ​16.3<0.001
       STS-PROM score (%)5.0 ​± ​3.44.9 ​± ​3.46.5 ​± ​4.3<0.001
      Echocardiographic assessment
       Aortic valve area (cm2)0.7 ​± ​0.30.7 ​± ​0.30.7 ​± ​0.30.38
       Mean gradient (mmHg)40.2 ​± ​17.440.2 ​± ​17.339.8 ​± ​19.80.83
       Left ventricular ejection fraction (%)55.2 ​± ​14.255.3 ​± ​14.251.8 ​± ​14.90.009
      Counts with percentages (%) or means ​± ​standard deviations are shown.
      Abbreviations: eGFR ​= ​estimated glomerular filtration rate; NYHA = New York Heart Association; STS-PROM = Society of Thoracic Surgeons-Predicted Risk of Mortality; TIA ​= ​Transient ischemic attack.

      3.2 Imaging assessments and TAVI procedure

      Imaging measurements as assessed by MSCT and procedural characteristics are summarized in Table 2. Patients with PAo had higher levels of calcium volume in the left ventricular outflow tract (31.4 ​± ​83.0 ​mm3 vs. 14.1 ​± ​39.7 ​mm3; p ​< ​0.001) and the mitral valve (1083.3 ​± ​1936.1 ​mm3 vs. 586.7 ​± ​1315.4 ​mm3; p ​= ​0.001) compared to patients with no PAo. Patients with PAo underwent TAVI by transfemoral access in 61.4% of cases, as compared to 92.6% of patients with no PAo (p ​< ​0.001). The transapical route was the most common non-femoral approach in patients with PAo (84.1%). Furthermore, patients with PAo more frequently underwent concomitant percutaneous coronary intervention compared to patients with no PAo (14.9% vs. 7.6%; p ​= ​0.01).
      Table 2Imaging and procedural characteristics.
      OverallNo-porcelain AortaPorcelain Aortap Value
      N ​= ​2199N ​= ​2085N ​= ​114
      Imaging characteristics
       Mean aortic annulus diameter (mm)24.1 ​± ​2.424.1 ​± ​2.424.0 ​± ​2.00.68
       LVOT calcium volume (mm3)15.0 ​± ​43.214.1 ​± ​39.731.4 ​± ​83.0<0.001
       AVC calcium volume (mm3)315.9 ​± ​340.2316.3 ​± ​344.9309.1 ​± ​240.30.83
       Mitral valve calcium volume (mm3)623.7 ​± ​1376.4586.7 ​± ​1315.41083.3 ​± ​1936.10.001
      Procedural characteristics
       Procedure time (min)56.3 ​± ​32.855.5 ​± ​32.070.8 ​± ​41.7<0.001
       Hospital stay (days)8.4 ​± ​4.78.3 ​± ​4.710.2 ​± ​5.7<0.001
       General anesthesia, n (%)433 (19.7)376 (18.1)57 (50.0)<0.001
       Concomitant PCI, n (%)176 (8.0)159 (7.6)17 (14.9)0.01
       Transcatheter cerebral embolic protection, n (%)8 (0.4)8 (0.4)0 (0.0)>0.999
      Access route
       Transfemoral, n (%)1999 (90.9)1929 (92.6)70 (61.4)<0.001
       Transapical, n (%)173 (7.9)136 (6.5)37 (32.5)<0.001
       Subclavian, n (%)15 (0.7)8 (0.4)7 (6.1)<0.001
       Carotid, n (%)3 (0.1)3 (0.1)0 (0.0)>0.999
       Transcaval, n (%)8 (0.4)8 (0.4)0 (0.0)>0.999
      Implanted device0.40
       Self-expanding, n (%)1021 (50.2)967 (50.3)54 (48.6)0.77
       Balloon-expandable, n (%)886 (43.6)833 (43.3)53 (47.7)0.38
       Mechanically-expanding, n (%)127 (6.2)123 (6.4)4 (3.6)0.31
      Postprocedural specifications
       Post-TAVI AR moderate or severe, n (%)145 (6.6)137 (6.6)8 (7.0)0.85
       Post-TAVI need for PPM within 30 days, n (%)394 (17.9)374 (17.9)20 (17.5)>0.999
      Counts with percentages (%) or means ​± ​standard deviations are shown. Abbreviations: AR ​= ​aortic regurgitation; AVC ​= ​aortic valvar complex; LVOT ​= ​left ventricular outflow tract; MSCT ​= ​multi slice computed tomography; PCI = Percutaneous coronary intervention; PPM = Permanent Pacemaker implantation; TAVI ​= ​Transcatheter aortic valve implantation.

      3.3 Clinical outcomes

      Event rates for clinical outcomes are presented in Table 3. The incidence of disabling stroke at one year was higher in patients with PAo (n ​= ​8, 7.2%) compared to those without PAo (n ​= ​61, 3.0%) (HRadj, 2.49; 95% CI, 1.12–5.55; p ​= ​0.03) (Graphical abstract). This difference emerged within 30 days after TAVI (PAo: n ​= ​7, 6.2% vs. no PAo: n ​= ​36, 1.7%; HRadj, 3.70; 95% CI, 1.52–9.03; p ​= ​0.004) (Fig. 2A), and was driven by high stroke rates in patients with PAo undergoing TAVI by alternative access route, while no association of PAo to strokes was observed in patients treated by femoral access (Online Table 1). Clinical outcomes stratified by device types were provided in Online Table 2. In patients with PAo balloon-expandable valves were primarily used in patients with transapical access and have been associated with higher rates of stroke compared to those without. Furthermore, similar rates of disabling stroke were observed in patients treated with early versus newer generation devices (Online Table 3). In a multivariable model, presence of PAo was identified as an independent predictor of disabling stroke at one year (HRadj, 2.47; 95% CI, 1.17–5.19; p ​= ​0.02) (Table 4).
      Table 3Short- and long-term clinical outcomes.
      No-porcelain AortaPorcelain AortaCrude hazard ratioAdjusted hazard ratio
      N ​= ​2084N ​= ​114HR (95% CI)p ValueHRadj (95% CI)p Value
      30 days follow-up
       All-cause death, n (%)54 (2.6)6 (5.3)2.06 (0.89-4.78)0.091.18 (0.47-2.94)0.72
      Cardiovascular death, n (%)46 (2.2)4 (3.6)1.61 (0.58-4.47)0.360.93 (0.31-2.76)0.90
       Disabling stroke, n (%)36 (1.7)7 (6.2)3.59 (1.60-8.06)0.0023.70 (1.52-9.03)0.004
       Myocardial infarction, n (%)15 (0.7)1 (0.9)1.22 (0.16-9.26)0.850.80 (0.10-6.78)0.84
       MACCE, n (%)83 (4.0)10 (8.8)2.23 (1.16-4.31)0.021.52 (0.75-3.09)0.25
       Life-threatening bleeding event, n (%)115 (5.5)15 (13.2)2.44 (1.42-4.17)0.0011.55 (0.86-2.79)0.15
       Major access site complications, n (%)234 (11.3)12 (10.6)0.94 (0.53-1.68)0.840.78 (0.43-1.43)0.43
      One-year follow-up
       All-cause death, n (%)237 (11.5)20 (17.8)1.59 (1.01-2.50)0.0470.94 (0.57-1.53)0.80
      Cardiovascular death, n (%)153 (7.5)16 (14.6)1.96 (1.17-3.28)0.011.18 (0.67-2.06)0.57
       Disabling stroke, n (%)61 (3.0)8 (7.2)2.48 (1.19-5.18)0.022.49 (1.12-5.55)0.03
       Myocardial infarction, n (%)35 (1.8)1 (0.9)0.53 (0.07-3.87)0.530.53 (0.07-4.07)0.54
       MACCE, n (%)221 (10.9)23 (20.8)2.00 (1.30-3.08)0.0021.39 (0.87-2.21)0.17
      Hazard ratios were determined by Cox regression for time-to-event data and adjusted for age, history of stroke or TIA, NYHA III or IV, peripheral artery disease, arterial hypertension, LVEF, STS-PROM score, and femoral access.
      Abbreviations: MACCE ​= ​Major adverse cardiovascular and cerebrovascular events (composite of cardiovascular death, disabling stroke, and myocardial infarction); LVEF ​= ​left ventricular ejection fraction; NYHA = New York Heart Association; STS-PROM = Society of Thoracic Surgeons-Predicted Risk of Mortality; TIA ​= ​Transient ischemic attack.
      Fig. 2
      Fig. 2Cumulative incidence of disabling stroke (A) and cardiovascular death (B) at one year after TAVI.
      Adjusted Hazard ratios (HRadj) and 95% confidence intervals (CI) from Cox regressions for time-to-event data, after adjusting for diabetes mellitus, age, history of stroke or TIA, NYHA III or IV, peripheral artery disease, arterial hypertension, LVEF, STS PROM score.
      Table 4Predictive factors for disabling stroke at one year.
      VariablesUnivariate analysisMultivariable analysisFinal included variablesMultivariable analysis
      HR (95% CI)p ValueHRadj (95% CI)p ValueHRadj (95% CI)p Value
      Porcelain Aorta2.50 (1.20-5.23)0.022.47 (1.11-5.53)0.03Porcelain Aorta2.47 (1.17-5.19)0.02
      Age (years)1.02 (0.98-1.06)0.421.01 (0.96-1.05)0.74History of CVEs1.81 (1.00-3.28)0.049
      History of CVEs2.01 (1.12-3.61)0.021.83 (1.00-3.36)0.051Post AR moderate/severe3.07 (1.64-5.72)<0.001
      Post AR moderate/severe3.11 (1.67-5.80)<0.0013.09 (1.64-5.83)<0.001Atrial fibrillation1.64 (1.02-2.66)0.04
      Gender (female)1.07 (0.67-1.72)0.780.91 (0.54-1.54)0.73
      Renal failure (eGFR<60)1.13 (0.68-1.88)0.631.02 (0.56-1.86)0.95
      Body mass index (kg/cm2)0.98 (0.94-1.03)0.401.01 (0.96-1.06)0.75
      Coronary artery disease0.93 (0.58-1.50)0.770.88 (0.53-1.48)0.64
      NYHA (III or IV)1.32 (0.77-2.25)0.321.29 (0.74-2.26)0.37
      Peripheral artery disease1.14 (0.58-2.23)0.701.03 (0.49-2.17)0.93
      Hypertension0.73 (0.39-1.35)0.310.75 (0.40-1.43)0.38
      LVEF (%)1.01 (0.99-1.03)0.341.01 (1.00-1.03)0.13
      STS-PROM score1.02 (0.95-1.08)0.611.00 (0.92-1.09)0.93
      Femoral access0.64 (0.32-1.28)0.210.76 (0.35-1.65)0.49
      Atrial fibrillation1.69 (1.05-2.71)0.031.67 (1.02-2.72)0.04
      AR ​= ​aortic regurgitation; COPD ​= ​chronic obstructive pulmonary disease; CVEs ​= ​cerebrovascular events; eGFR ​= ​estimated glomerular filtration rate; LVEF ​= ​left ventricular ejection fraction; NYHA = New York Heart Association; STS-PROM = Society of Thoracic Surgeons-Predicted Risk of Mortality.
      Final multivariable model retains covariates with p ​< ​0.2.
      The one-year cardiovascular and all-cause mortality did not differ between groups (all-cause mortality: HRadj, 0.94; 95% CI, 0.57–1.53; p ​= ​0.80; cardiovascular mortality: HRadj, 1.18; 95% CI, 0.67–2.06; p ​= ​0.57) (Fig. 2B).

      4. Discussion

      The pertinent findings of the present analysis can be summarized as follows. PAo was documented in 5.2% of patients undergoing TAVI and was associated with an increased risk of periprocedural disabling stroke. The difference was driven by higher PAo-associated rates of disabling stroke in patients treated by alternative access route. PAo was identified as an independent predictor of disabling stroke at one year. Cardiovascular- and all-cause mortality, as well as rates of access site complications and life-threatening bleedings were comparable in patients with and without PAo at 30 days and one year.
      Previous studies using various definitions of PAo indicated a prevalence among TAVI patients ranging from 4.2 to 19.0%,
      • Useini D.
      • Haldenwang P.
      • Schlömicher M.
      • et al.
      Mid-term outcomes after transapical and transfemoral transcatheter aortic valve implantation for aortic stenosis and porcelain aorta with a systematic review of transfemoral versus transapical approach.
      ,
      • Nakasu A.
      • Greason K.L.
      • Nkomo V.T.
      • et al.
      Transcatheter aortic valve insertion in patients with hostile ascending aorta calcification.
      • Buz S.
      • Pasic M.
      • Unbehaun A.
      • et al.
      Trans-apical aortic valve implantation in patients with severe calcification of the ascending aorta.
      • Kempfert J.
      • Van Linden A.
      • Linke A.
      • et al.
      Transapical aortic valve implantation: therapy of choice for patients with aortic stenosis and porcelain aorta?.
      • Rodés-Cabau J.
      • Webb J.G.
      • Cheung A.
      • et al.
      Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience.
      • Zahn R.
      • Schiele R.
      • Gerckens U.
      • et al.
      Transcatheter aortic valve implantation in patients with "porcelain" aorta (from a Multicenter Real World Registry).
      and reported an incidence of stroke in these patients between 1.6 and 16.1%.
      • Useini D.
      • Haldenwang P.
      • Schlömicher M.
      • et al.
      Mid-term outcomes after transapical and transfemoral transcatheter aortic valve implantation for aortic stenosis and porcelain aorta with a systematic review of transfemoral versus transapical approach.
      ,
      • Buz S.
      • Pasic M.
      • Unbehaun A.
      • et al.
      Trans-apical aortic valve implantation in patients with severe calcification of the ascending aorta.
      • Kempfert J.
      • Van Linden A.
      • Linke A.
      • et al.
      Transapical aortic valve implantation: therapy of choice for patients with aortic stenosis and porcelain aorta?.
      • Rodés-Cabau J.
      • Webb J.G.
      • Cheung A.
      • et al.
      Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience.
      In an analysis of 52 matched pairs of patients with severe AS and PAo, TAVI was associated with a borderline lower periprocedural mortality compared to SAVR, while rates of stroke were comparable.
      • Ramirez-Del Val F.
      • Hirji S.A.
      • Yammine M.
      • et al.
      Effectiveness and safety of transcatheter aortic valve implantation for aortic stenosis in patients with "porcelain" aorta.
      The largest prospective cohort study in patients with PAo undergoing TAVI included 147 patients (82% with transfemoral access) and documented a significantly higher rate of myocardial ischemia and a trend towards an increased risk of periprocedural stroke in patients with as compared to those without PAo.
      • Zahn R.
      • Schiele R.
      • Gerckens U.
      • et al.
      Transcatheter aortic valve implantation in patients with "porcelain" aorta (from a Multicenter Real World Registry).
      The study was limited to in-hospital outcomes, used no standardized definition of PAo, and clinical events were not independently adjudicated. In the present study, transfemoral access was performed in 61% of patients with PAo. While we found no difference in myocardial infarction in patients with vs. without PAo, we documented a significantly increased risk of disabling stroke in patients with PAo.
      Small case series advocated for a transapical approach as a default strategy for TAVI in patients with PAo based on the rationale to forego manipulation with the delivery catheter in the calcified aorta.
      • Useini D.
      • Haldenwang P.
      • Schlömicher M.
      • et al.
      Mid-term outcomes after transapical and transfemoral transcatheter aortic valve implantation for aortic stenosis and porcelain aorta with a systematic review of transfemoral versus transapical approach.
      Intriguingly, in our cohort, rates of disabling stroke were particularly high among patients treated by transapical or transsubclavian access, while rates of disabling stroke in PAo patients treated by transfemoral route were comparable to the rates in patients without PAo. Given the modest numbers and the non-randomized treatment allocation, these results must be interpreted with caution. Data from the PARTNER 2 trial showed disabling stroke at 30 days in 2.3% of patients treated by transfemoral route as compared to 6.0% of patients treated by transthoracic route.
      • Leon M.B.
      • Smith C.R.
      • Mack M.
      • et al.
      Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.
      In contrast, propensity score matched analyses from the PARTNER I trial and the National Inpatient Sample in the United States indicated comparable risks of stroke in patients treated by transfemoral vs. transapical approach, respectively.
      • Blackstone E.H.
      • Suri R.M.
      • Rajeswaran J.
      • et al.
      Propensity-matched comparisons of clinical outcomes after transapical or transfemoral transcatheter aortic valve replacement: a placement of aortic transcatheter valves (PARTNER)-I trial substudy.
      ,
      • Kumar N.
      • Khera R.
      • Fonarow G.C.
      • Bhatt D.L.
      Comparison of outcomes of transfemoral versus transapical approach for transcatheter aortic valve implantation.
      In line, there was no difference in stroke among patients undergoing TAVI as a function of transfemoral, transapical or transsubclavian approach in the FRANCE 2 registry.
      • Gilard M.
      • Eltchaninoff H.
      • Iung B.
      • et al.
      Registry of transcatheter aortic-valve implantation in high-risk patients.
      Our findings challenge the notion, that a transapical approach is preferred over transfemoral access for TAVI in patients with PAo. Localization, extent, and distribution of calcification in the ascending aorta and the aortic arch warrant an informed decision on the preferred access route on an individual basis. In the present analysis, moderate or greater post-TAVI aortic regurgitation was identified as a strong predictor of disabling stroke. This finding may be confounded by the association of left ventricular outflow tract calcification with both aortic regurgitation and stroke. In addition, balloon-expandable valves have been associated with higher rates of stroke compared to self-expanding valves and were primarily used in patients with transapical access.
      The risk of stroke continues to be of relevant concern in TAVI patients, in particular in those with PAo. Strategies to mitigate the risk of stroke include the use of transcatheter cerebral embolic protection (TCEP) devices. Previous studies indicated that the use of TCEP devices was independently associated with a lower risk of ischemic strokes after TAVI.
      • Seeger J.
      • Kapadia S.R.
      • Kodali S.
      • et al.
      Rate of peri-procedural stroke observed with cerebral embolic protection during transcatheter aortic valve replacement: a patient-level propensity-matched analysis.
      • Megaly M.
      • Sorajja P.
      • Cavalcante J.L.
      • et al.
      Ischemic stroke with cerebral protection system during transcatheter aortic valve replacement.
      • Giustino G.
      • Sorrentino S.
      • Mehran R.
      • Faggioni M.
      • Dangas G.
      Cerebral embolic protection during TAVR: a clinical event meta-analysis.
      Two ongoing prospective randomized outcome trials (NCT02895737 and NCT02536196) are anticipated to provide concluding evidence on the effectiveness of TCEP. Nevertheless, careful patient selection for implantation of TCEP devices remains crucial.
      • Bagur R.
      • Solo K.
      • Alghofaili S.
      • et al.
      Cerebral embolic protection devices during transcatheter aortic valve implantation: systematic review and meta-analysis.
      The present study provides evidence that patients with PAo have an increased risk of stroke compared to patients with no PAo, and may therefore particularly benefit from such devices.

      4.1 Study limitations

      The findings of our analysis have to be interpreted in light of several limitations. Our analysis is based on a relatively modest number of patients from a single center. However, our prospective registry is considerably larger than the cohorts of previous analyses and adheres to high standards of data quality in terms of data collection, standardized follow-up, and independent event adjudication at regular time intervals. Furthermore, exclusion of patients who did not undergo MSCT might lead to sample bias, as this might apply particularly to patients with indications for urgent and emergency TAVI. Additionally, our endpoints are limited to events with high impact on the patient's well-being. Occult strokes, also affecting the clinical outcome, were not systematically assessed. Confounders, such as the higher rate of balloon-expandable valves in patients undergoing transapical TAVI might have contributed to the worse outcomes in these patients, since balloon-expandable valves have been associated with a higher risk of stroke.
      • Thiele H.
      • Kurz T.
      • Feistritzer H.J.
      • et al.
      Comparison of newer generation self-expandable vs. balloon-expandable valves in transcatheter aortic valve implantation: the randomized SOLVE-TAVI trial.
      Randomized comparison of different therapeutic approaches in patients with PAo like access routes or prostheses types was beyond the scope of our study and could be addressed in future studies.

      4.2 Conclusions and clinical implications

      Patients with PAo are more likely to suffer from disabling stroke after TAVI, while presence of PAo was not associated with cardiovascular- and all-cause mortality within one year. Our findings challenge the notion that a transapical approach should be preferred in patients with PAo.

      Funding

      None.

      Disclosures

      Dr. Windecker reports research and educational grants to the institution from Abbott, Amgen, BMS, Bayer, Boston Scientific, Biotronik, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Johnson&Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, Sinomed. He serves as unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/executive committee group of several investigated-initiated trials that receive funding by industry without impact on his personal remuneration. He is an unpaid member of the Pfizer Research Award selection committee in Switzerland. Dr. Stortecky reports having received research grants to the institution by Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific, and speaker fees from Boston Scientific, Teleflex, and BTG. Dr. Praz has received travel expenses from Edwards Lifesciences, Abbott Medical, and Polares Medical. Dr. Pilgrim reports having received research grants to the institution from Boston Scientific, Biotronik, and Edwards Lifesciences and speaker fees from Boston Scientific and Biotronik, and consultancy from HighLife SAS; he is a proctor for Boston Scientific and Medtronic. All other authors have no relationships relevant to the contents of this article to disclose.

      Acknowledgements

      None.

      Appendix A. Supplementary data

      The following is the supplementary data to this article:

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