Immediate and mid-term results of transfemoral aortic valve implantation using either the Edwards Sapien™ transcatheter heart valve or the Medtronic CoreValve® System in high-risk patients with aortic stenosis

Archives of Cardiovascular Disease (2010) 103, 236—245 CLINICAL RESEARCH Immediate and mid-term results of transfemoral aortic valve implantation using either the Edwards SapienTM transcatheter heart valve or the Medtronic CoreValve® System in high-risk patients with aortic stenosis Résultats immédiats et à moyen terme de l’implantation valvulaire aortique transfémorale utilisant la prothèse Edwards SapienTM transcatheter heart valve ou la prothèse Medtronic CoreValve® System chez des patients ayant une sténose aortique à haut risque chirurgical David Attias a,∗, Dominique Himbert a, Gregory Ducrocq a, Delphine Détaint a, Nawwar Al-Attar b, Bernard Iung a, Fady Francis c, Jean-Michel Maury c, Eric Brochet a, Daniel Enguerrand d, Patrick Nataf b, Alec Vahanian a a Departments of Cardiology, Bichat Hospital, Assistance publique—Hôpitaux de Paris, 46, rue Henri-Huchard, 75018 Paris, France b Cardiovascular Surgery, Assistance publique—Hôpitaux de Paris, Paris, France c Thoracic and Vascular Surgery, Assistance publique—Hôpitaux de Paris, Paris, France d Anaesthesiology, Bichat Hospital, Assistance publique—Hôpitaux de Paris, Paris, France Received 25 November 2009; received in revised form 4 February 2010; accepted 18 March 2010 Abbreviations: AVR, aortic valve replacement; NYHA, New York Heart Association; STS-PROM, Society of Thoracic Surgeons Predicted Risk of Mortality; TAVI, transcatheter aortic valve implantation; TEE, transesophageal echocardiography; THV, transcatheter heart valve; TTE, transthoracic echocardiography; TF, transfemoral. ∗ Corresponding author. Fax: +33 1 40 25 88 65. E-mail address: david.attias@bch.aphp.fr (D. Attias). 1875-2136/$ — see front matter © 2010 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.acvd.2010.03.006 Transfemoral aortic valve implantation KEYWORDS Aortic stenosis; Transfemoral; Transcatheter aortic valve implantation MOTS CLÉS Implantation valvulaire aortique par cathéter ; Voie transfémorale ; Rétrécissement aortique 237 Summary Objective. — We sought to describe the results of transfemoral aortic valve implantation using either the SapienTM prosthesis or the CoreValve® System. Background. — Results of transfemoral aortic valve implantation using both commercially available prostheses have rarely been studied. Patients. — Of 236 patients at high-risk or with contraindications to surgery, consecutively referred for transcatheter aortic valve implantation between October 2006 and June 2009, 83 were treated with transfemoral aortic valve implantation. The SapienTM was the only prosthesis available until May 2008 and, since then, was used as the first option, while the CoreValve® System was used when contraindications to the SapienTM prosthesis were present. Results. — Patients were aged 81 ± 9 years, 98% in New York Heart Association classes III/IV, with predicted surgical mortalities of 26 ± 14% using the EuroSCORE and 15 ± 8% using the Society of Thoracic Surgeons Predicted Risk of Mortality score. Seventy-two patients were treated with the SapienTM prosthesis and 11 with the CoreValve® System. The valve was implanted in 94% of the cases. Thirty-day mortality was 7%. Overall, 1- and 2-year survival rates were 78 ± 5% and 71 ± 7%, respectively. Among patients treated with the SapienTM , the 1-year survival rate was 67 ± 12% in the first 20% of patients versus 86 ± 5% in the last 80% of patients (p = 0.02). In univariate analysis, early experience was the only significant predictor of 1-year mortality. Conclusion. — Combining the use of the SapienTM and the CoreValve® prostheses increases the number of patients who can be treated by transfemoral aortic valve implantation and provides satisfactory results at 2 years in this high-risk population. The results are strongly influenced by experience. © 2010 Elsevier Masson SAS. All rights reserved. Résumé Introduction. — Les résultats d’une stratégie d’implantation valvulaire aortique transfémorale utilisant l’une ou l’autre des deux prothèses commercialisées ont été peu décrits. Objectif. — Décrire les résultats de l’implantation valvulaire aortique transfémorale utilisant soit la prothèse SapienTM soit la prothèse CoreValve® System. Patients. — Sur 236 patients ayant un haut risque ou une contre-indication chirurgicale, consécutivement adressés entre octobre 2006 et juin 2009 pour implantation valvulaire aortique par cathéter, 83 ont été traités par voie transfémorale. La prothèse SapienTM était la seule disponible jusqu’en mai 2008. Après mai 2008, elle a été utilisée en première intention tandis que la prothèse CoreValve® System a été utilisée en cas de contre-indication à la prothèse SapienTM . Résultats. — L’âge moyen des patients était de 81 ± 9 ans ; 98 % des patients étaient en classe III ou IV de la New York Heart Association (NYHA) avec un score prédit de mortalité chirurgicale de 26 ± 14 % selon l’EuroSCORE et 15 ± 8 % selon le score de la Society of Thoracic Surgeons. Soixante-douze patients ont été traités avec la prothèse SapienTM et 11 avec la prothèse CoreValve® System. La prothèse a été implantée avec succès dans 94 % des cas. La mortalité à 30 jours a été de 7 %. Au total, les survies à un et à deux ans ont été respectivement de 78 ± 5 % et de 71 ± 7 %. Parmi les patients traités avec la prothèse SapienTM , la survie à un an a été de 67 ± 12 % pour les premiers 20 % contre 86 ± 5 % pour les derniers 80 % (p = 0,02). En analyse univariée, l’expérience débutante était le seul facteur prédictif de mortalité à un an. Conclusion. — L’utilisation combinée des prothèses SapienTM et CoreValve® augmente le nombre de patients pouvant être traités par voie transfémorale et donne des résultats satisfaisants à deux ans dans cette population à haut risque. Les résultats sont fortement influencés par l’expérience des opérateurs. © 2010 Elsevier Masson SAS. Tous droits réservés. Introduction Aortic stenosis is the most frequent valvular heart disease in Western countries [1]. According to guidelines, surgical aortic valve replacement (AVR) is the reference treatment for patients with severe symptomatic aortic stenosis [2,3]. Seven years after the first-in-man report [4], transcatheter aortic valve implantation (TAVI) has emerged as a credible alternative therapy for patients with aortic stenosis who are considered at high-risk or with contraindications for conventional AVR [5]. In most cases, procedures are performed via transfemoral (TF) or transapical approaches 238 [6—8], but other approaches (e.g., subclavian, transiliac) are being evaluated [9]. Among these possibilities, the TF approach is the most frequently used [10,11]. However, no study reporting the results of TF TAVI using either of the two commercially available prostheses has been published. The aim of this study was to describe the outcomes of 83 patients consecutively treated with TF TAVI using either the Edwards SapienTM transcatheter heart valve (THV) (Edwards Lifesciences Inc., Irvine, CA, USA) or the Medtronic CoreValve® System (Medtronic Int. Trading, Tolochenaz, Switzerland). Methods Patients From October 2006 to June 2009, all high-risk patients with severe symptomatic aortic stenosis evaluated for TAVI underwent multidisciplinary clinical evaluation, transthoracic echocardiography (TTE) and, if necessary, transesophageal echocardiography (TEE), coronary angiography, aortic and femoro-iliac angiography and multislice computed tomography. The decision to perform TAVI was taken in patients with contraindications to, or at high-risk for AVR (EuroSCORE ≥20% or Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] ≥10%); life expectancy >1 year [12,13]; anatomy suitable for intervention [5]; and no need for coronary artery bypass surgery. The TF approach was considered as the first option [10], and transapical, subclavian or transiliac in patients with contraindications to the TF approach, including: previous aortofemoral bypass, bulky aortic atherosclerosis, porcelain thoracic aorta, a minimal luminal diameter <6 mm for the 18 Fr sheaths, <7 mm for the 22 Fr sheaths and <8 mm for the 24 Fr sheaths, vessel kinking or severe angulation and severe vascular calcification. From October 2006 to May 2008, the Edwards SapienTM THV was the only prosthesis used. From May 2008, the Medtronic CoreValve® System was used as an alternative in cases of technical contraindications to the SapienTM THV: (1) femoro-iliac diameters too small, comprised between 6 and 7 or 8 mm (according to the size of the prosthesis to be implanted); (2) aortic annulus diameters too large, comprised between 25 and 27 mm. In patients with technical contraindications to any TAVI, AVR was reconsidered if the operative risk was not deemed prohibitive. In patients who were too frail to undergo any invasive intervention or with comorbidities that clearly limited short-term life expectancy or precluded future quality of life (mainly malignancies and cognitive disorders), a medical treatment was decided upon. Transfemoral transcatheter aortic valve implantation (TAVI) Procedures were performed under general anaesthesia, with fluoroscopic and TEE guidance. Patients received aspirin 75 mg once daily and clopidogrel 75 mg once daily for at least 4 days before the procedure, or a loading dose of clopidogrel D. Attias et al. 300 mg the day before the procedure. Heparin 70 UI/kg was given intravenously before retrograde crossing of the aortic valve. Edwards SapienTM transcatheter heart valve (THV) Vascular access was performed using two different methods over time: a percutaneous X-ray-guided puncture for the first 19 patients; then a surgical, view-guided puncture for the last 53 patients. A femoral arterial 5 Fr sheath was placed in the opposite groin to allow pressure monitoring and aortic angiograms through a Pigtail catheter, and a venous 8 Fr sheath to allow right ventricular rapid pacing. X-ray-guided puncture X-ray-guided puncture was performed under fluoroscopic guidance overlying the upper part of the bony femoral head. A 6 Fr sheath (Terumo® , Tokyo, Japan) was placed in the common femoral artery and after stepwise dilatation with 8, 10 and 12 Fr dilatators, a 14 Fr sheath (Cook® , Bloomington, IN, USA) was placed to allow balloon dilatation of the aortic valve. Thereafter, further stepwise dilatation with 16, 18, 20, 22 (±24) Fr dilatators was performed on an Amplatz Extra Stiff wire (Cook® , Bjaeverstov, Denmark) before introducing the 22 or 24 Fr sheath on the same wire. The sheath was pushed through the femoroiliac axis to the aorta, using a gentle twisting motion of the catheter under fluoroscopic control. The artery was closed surgically at the end of the procedure. View-guided puncture The common femoral artery was exposed and dissected free just below the inguinal ligament to gain access to a soft area of the artery. Proximal and distal control of the vessel was obtained with vascular loops. After inspection and manual palpation of the artery, a puncture was made through the skin and subcutaneous tissues 2 cm below the primary incision, providing a firm anchor for the sheath. The needle was then inserted in the anterior vessel wall of the common femoral artery avoiding important side-branches and bulky plaques. Then, the 22 or 24 Fr sheath was introduced on an Amplatz Extra Stiff wire or on an Extra Back Up Meier wire (Boston Scientific® , Miami, USA), under view control, without predilatation, and pushed to the descending aorta in the same fashion as described above. Then, after retrograde crossing and predilatation of the native valve, the prosthesis was pushed by a flexible catheter RetroFlexTM (Edwards Lifesciences® , Irvine, CA, USA), positioned within the aortic valve using fluoroscopic and TEE guidance, and then delivered by balloon inflation under rapid ventricular pacing. After valve implantation, the sheath was withdrawn on the stiff wire to the upper part of the external iliac artery. An angiogram in an anteroposterior view was then performed to study the abdominal aorta, the common iliac, and the first 2 cm of the external iliac artery. Before complete withdrawal of the sheath, the access site in the common femoral artery and the visible portion of the external iliac artery were inspected to detect arterial wall disruptions. In the absence of any vascular complications, the common femoral artery was clamped and repaired with polypropylene sutures. After complete surgical vascular repair, a final Transfemoral aortic valve implantation angiogram was performed using a pigtail introduced in the opposite groin. Medtronic CoreValve® System Access and closure of the femoral artery were performed percutaneously in all cases, using the Prostar XL® 10F (Abbott Vascular® Devices Inc., Chicago, USA) with the preclosing technique. An 18 F sheath was inserted and the procedure was similar to that with the Edwards SapienTM prosthesis until aortic balloon predilatation. Then, the prosthesis was pushed through the aorta to the left ventricle. The outer sheath was slowly retracted, allowing the deployment of the self-expanding prosthesis without rapid pacing. During the progressive deployment of the prosthesis, positioning could be corrected with gentle pull or push, according to the fluoroscopic and TEE guidance. Then, final retraction of the sheath led to complete delivery of the prosthesis. After valve implantation, confirmation of the vascular integrity was obtained as described above, and the femoral artery was closed using the Prostar XL® . After the procedure, patients were directed to the intensive care unit for at least 48 hours. Physical examination was performed every 6 hours to detect signs of limb ischemia. Antiplatelet therapy consisted of aspirin 75 mg and clopidogrel 75 mg daily. In case of surgical closure, inguinal drainage was withdrawn after 48 hours if blood loss was <50 cc/24 h. Standing was usually authorized after 48 hours. At discharge, patients received aspirin plus clopidogrel for 3 to 6 months, and then only one antiplatelet agent was continued. In patients requiring long-term oral anticoagulation, only one antiplatelet agent was used. Follow-up Hospital clinical and echocardiographic data were obtained before discharge. All adverse events were prospectively recorded. After the hospital phase, clinical and TTE followup were obtained in all survivors at 1 to 3 months, 6 months, 1 year and then annually. Outcomes Outcomes were described according to the guidelines for reporting mortality and morbidity after cardiac valve interventions [14]. Implantation success was defined by valve implantation in the correct position. Major vascular complications were defined as lesions requiring immediate or delayed vascular interventions other than a simple arterial suture, or leading to hospital death. Statistical analysis Data are expressed as mean ± S.D., except for the length of follow-up and length of stay in hospital, which are expressed as median [25th—75th percentiles]. Categorical variables were compared by the chi-square test or Fisher’s exact test. Late survival was analysed using Kaplan—Meier methods and survival rates are given with their standard errors. To assess experience a binary variable was used to separate the 239 first 20% (n = 15) from the last 80% (n = 57) of patients treated with the Edwards SapienTM THV. Analysis of the predictive factors of late survival was performed by a univariate analysis using a log-rank test. The 11 patients treated with the Medtronic CoreValve® System were excluded from this analysis because their implantation began in May 2008. All tests were two-sided. A p value <0.05 was considered to indicate a statistically significant difference. Statistical analysis was performed using statistical software Statistica version 5.0 (Statsoft Inc., Tulsa, Oklahoma). Results Patients Of the 236 patients who were at high-risk or had contraindications to AVR, 83 (35%) were treated by TF TAVI, 72 (30%) using the SapienTM THV and 11 (5%) the CoreValve® System. Other patients who underwent TAVI were treated by transapical (n = 35, 15%) or subclavian/transiliac retroperitoneal (n = 1/2, 1%) access. Thirty (13%) patients were reoriented toward conventional AVR, while 85 (36%) were considered too frail, with a life expectancy too short to undergo any invasive intervention, or had technical contraindications to both TAVI and AVR, and were treated medically. The population studied here consisted of the 83 patients who were treated by TF TAVI. Its characteristics are detailed in Table 1. Overall, the population was at high surgical risk. Mean age was 81 ± 9 years. Nearly all patients (98%) were in New York Heart Association (NYHA) class III or IV. The majority had coronary artery disease and more than two extracardiac comorbidities. The SapienTM THV was used in 72 patients. Since May 2008, the CoreValve® System was chosen in 11 patients because of contraindications to the SapienTM THV: aortic annulus diameter too large (>25 and ≤27 mm) in six cases; femoro-iliac diameters too small (<7 or 8 mm, ≥6 mm) in five cases. The expected operative mortality rates were 26 ± 14% according to the EuroSCORE and 15 ± 8% according to the STS score, with no significant difference between patients treated with the SapienTM THV and the CoreValve® System. All patients (n = 8) with a EuroSCORE <20% and an STS score <10% had contraindications to AVR, which were not taken into account by these scores: severe respiratory failure (n = 5), chest radiation sequellae (n = 1), intracerebral aneurysm (n = 1), morbid obesity (n = 1). Thirty-day outcomes Thirty-day outcomes are detailed in Table 2. Implantation success was achieved in 78 (94%) patients. Technical failures occurred with the SapienTM THV. Reasons for failure included inability to pass the iliac artery in three patients, to cross the aortic valve with the prosthesis in one patient, and haemopericardium in one patient due to perforation of the left ventricle by the wire, leading to intraprocedural death. There was neither prosthesis embolization nor conversion to on-pump surgical AVR. Immediately after implantation, paravalvular leaks were frequent, but were grade ≥III in only three (4%) patients. 240 Table 1 D. Attias et al. Baseline characteristics of the study population. Overall (n = 83) SapienTM THV (n = 72) CoreValve® System (n = 11) P Age (years, mean ± S.D.) 81 ± 9 81 ± 9 79 ± 7 0.26 Women 39 (47) 36 (50) 3 (27) 0.20 New York Heart Association class II III IV 2 (2) 45 (54) 36 (43) 2 (3) 41 (57) 29 (40) 0 (0) 4 (36) 7 (64) 0.32 Coronary artery disease Previous myocardial infarction Previous PCI Previous CABG 42 11 16 18 (51) (13) (19) (22) 36 (50) 9 (13) 13 (18) 17 (24) 6 2 3 1 1 0.63 0.44 0.44 Peripheral artery disease 23 (28) 20 (28) 3 (27) 1 Renal failure 26 (31) 21 (29) 5 (45) 0.3 Severe COPD 27 (33) 21 (29) 6 (26) 0.16 Cancer 27 (32) 20 (28) 7 (64) 0.04 Porcelain aorta 6 (7) 4 (6) 2 (18) 0.18 43 (52) 36 (50) 7 (64) 0.52 0.69 ± 0.18 0.66 ± 0.16 0.89 ± 0.21 0.005 Aortic valve area (cm /m BSA) 0.40 ± 0.10 0.38 ± 0.10 0.49 ± 0.10 0.009 Mean gradient (mmHg) 52 ± 16 53 ± 16 46 ± 13 0.13 Left ventricular ejection fraction (%) 52 ± 15 51 ± 15 58 ± 13 0.15 Aortic annulus diameter (mm) 23 ± 2 23 ± 2 24 ± 3 0.46 Bicuspid aortic valve 3 (4) 1 (1) 2 (18) 0.04 Minimal arterial diameter (mm) 7.8 ± 1 7.9 ± 1 7±1 0.12 Logistic EuroSCORE (%), mean ± S.D. (range) 26 ± 14 (3—90) 26 ± 15 (3—90) 23 ± 8 (9—37) 0.24 STS-PROM (%), mean ± S.D. (range) 15 ± 8 (3—47) 15 ± 7 (3—35) 14 ± 15 (6—47) 0.93 Two or more comorbidities 2 Aortic valve area (cm ) 2 2 (55) (18) (27) (9) Values are expressed as n (%) unless otherwise stated. BSA: body surface area; CABG: coronary artery bypass grafting; COPD: chronic obstructive pulmonary disease; PCI: percutaneous coronary intervention; S.D.: standard deviation; STS-PROM: Society of Thoracic Surgeons Predicted Risk of Mortality; TAVI: transcatheter aortic valve implantation; THV: transcatheter heart valve. In one patient, emergent implantation of a second prosthesis into the first one (‘‘valve after valve’’) was necessary, due to a massive intravalvular regurgitation induced by balloon redilatation performed to treat severe paravalvular leak. The most frequent complications were vascular, overall 12%; all occurred with the SapienTM THV. There were four iliac dissections, of which one led to death 4 days after surgical grafting, and six femoral injuries at the entry site. All of these complications were managed during the index procedure by surgical grafting (n = 6), stenting (n = 2) or combined stenting and surgical grafting (n = 2). These vascular complications led to transfusion in seven patients. There were neither aortic dissections nor perforations. Strokes occurred in 5% of patients, and led to disabling sequellae in one (1%) patient only. Complete atrioventricular block requiring pacemaker implantation occurred in 8% of the cases, and tended to be more frequent after CoreValve® System implantation than after SapienTM THV (18% vs 7%, p = 0.23). One atrioventricular block occurred at 4 days, and one patient had a syncope 2 weeks after the procedure, which was also attributed to delayed complete atrioventricular block. Causes of deaths are detailed in Table 3. All-cause 30-day mortality rate was 7% (n = 6). Late outcomes Median follow-up was 9 months (range: 1—36 months) [3—15]. Ten deaths occurred after 30 days: three due to extracardiac causes (infections), four due to heart failure, of which two occurred in inoperable patients with one grade II and one grade III aortic regurgitations, and three were sudden, unexplained (Table 3). One- and 2-year survival rates Transfemoral aortic valve implantation Table 2 241 Thirty-day outcomes in the study population. Overall (n = 83) SapienTM THV (n = 72) CoreValve® System (n = 11) P 78 (94) 67 (93) 11 (100) 1 1.7 ± 0.4 1.7 ± 0.4 1.9 ± 0.6 0.54 Aortic valve area (cm /m ) 0.98 ± 0.25 0.96 ± 0.20 1.13 ± 0.40 0.43 Mean gradient (mmHg) 11 ± 4 12 ± 4 10 ± 6 0.5 Paravalvular aortic regurgitation Grade 0 Grade I Grade II Grade III/IV 21 41 13 3 16 37 12 2 5 4 1 1 ‘‘Valve after valve’’ 1 (1) 1 (10) 0 Femoral access/closure All percutaneous X-ray-guided puncture + surgical closure View-guided puncture + surgical closure 11 (14) 21 (26) 51 (61) 0 21 (30) 51 (71) 11 (100) 0 0 Major vascular complications 10 (12) 10 (14) 0 0.34 Stroke 4 (5) 4 (6) 0 1 2 (2) 2 (3) 0 1 Heart block 7 (8) 5 (7) 2 (18) 0.23 Death per-procedure 2 (2) 2 (3) 0 0.09 30-day mortality 6 (7) 4 (6) 2 (18) 0.23 Length of hospital stay (days), median [25th—75th percentiles]b 12 [9—16] 11 [7—12] 11 [9—16] 0.09 Implantation success 2 Aortic valve area (cm ) 2 2 Tamponade a 0.3 0.20 Values are expressed as n (%) or mean ± S.D., unless otherwise stated. S.D.: standard deviation; THV: transcatheter heart valve. Requiring pacemaker implantation. b From procedure to discharge. a were 78 ± 5% and 71 ± 7%, respectively (Fig. 1). In univariate analysis, early experience was the only significant predictor of 1-year mortality: 1-year survival was 67 ± 12% in the 15 first patients versus 86 ± 5% in the 57 last patients (p = 0.02) treated with the Edwards SapienTM THV (Fig. 2). Non-lethal valve-related events consisted only in one case of endocarditis due to Streptococcus bovis that occurred 5 months after the procedure and was successfully treated medically, with no valve dysfunction. There was no reintervention, haemolysis or permanent valve-related impairment. No structural valve deterioration or dysfunction was observed. At last follow-up of the 66 survivors, 24 (36%) were in NYHA class I, 30 (46%) in class II, seven (11%) in class III and five (7%) in class IV (Fig. 3). In the latter (four men, 83 ± 10 years), reasons for remaining in class IV were not due to a poor haemodynamic result of TAVI (aortic valve area: 1.8 ± 0.1 cm2 ; mean gradient: 8 ± 3 mmHg). Persistence of disabling symptoms was attributed to severe pulmonary disease in three cases (one of whom had idiopathic pulmonary hypertension), to depressed left ventricular ejection fraction (35%) unchanged after TAVI, and to left ventricular diastolic dysfunction in one case. Figure 1. Two-year survival after transfemoral transcatheter aortic valve implantation (TAVI). Kaplan—Meier survival in the 83 patients treated with transfemoral aortic valve implantation (SapienTM transcatheter heart valve [THV] and CoreValve® System). 242 Table 3 D. Attias et al. Causes of death in 83 patients treated with transfemoral aortic valve implantation. Time/valve In-hospital SapienTM SapienTM CoreValve® CoreValve® SapienTM SapienTM Post-discharge CoreValve® SapienTM SapienTM SapienTM SapienTM SapienTM SapienTM SapienTM SapienTM SapienTM a Days to death 0 0 0 0 1 4 46 79 82 150 165 222 263 347 421 445 Cause of death Haemopericardium (left ventricular perforation)Intraprocedural death Hemopericardium (annular rupture) Intraprocedural death Massive aortic regurgitation, left ventricular failure Subaortic obstruction, left ventricular failure Sudden, unexplained death Iliac dissection Multiorgan failure after vascular surgery Heart failure Chronic renal failure, sudden unexplained death Urinary infection Sudden death Pulmonary infection Pulmonary infection (after neurosurgery) Sudden, unexplained death Heart failure (grade II paraprosthetic aortic regurgitationa ) Heart failure Heart failure (grade III paraprosthetic aortic regurgitationa ) As initially determined by transesophageal echocardiography and then evaluated by transthoracic echocardiography during follow-up. Discussion To the best of our knowledge, this prospective study is the first to report the outcomes of patients with severe symptomatic aortic stenosis and high-risk for or contraindications to AVR, after TF TAVI using either the SapienTM THV or the CoreValve® System. Owing to the complementarities of the devices, being able to use both of them increased the number of patients who could be treated with the TF approach. Overall, late valve-related events were rare and clinical out- Figure 2. One-year survival after transfemoral transcatheter aortic valve implantation (TAVI) in the first versus the last patients. Kaplan—Meier survival in the first 20% of patients treated with the SapienTM transcatheter heart valve (THV) compared to the last 80%. comes satisfactory in terms of survival as well as functional improvement. SapienTM transcatheter heart valve (THV) and CoreValve® System Besides their differences in terms of stent and prosthesis materials, and implantation technique, both devices are not strictly designed for the same anatomical profiles. As compared with the 22/24 Fr sheaths necessary to accommodate Figure 3. Functional status before and after transcatheter aortic valve implantation (TAVI). Evolution of the New York Heart Association (NYHA) functional class in patients between the preprocedure condition and the last follow-up, after TAVI. Transfemoral aortic valve implantation 243 the 23/26 mm SapienTM THV, the 18 Fr sheath of the CoreValve® System allows a larger number of patients to be treated with the TF approach. This is of particular importance because vascular access remains the main cause for contraindications, failures and complications of the TF approach. Similarly, patients with large (25—27 mm) aortic annulus diameters are eligible for the CoreValve® System only, while, conversely, those with small (18—20 mm) diameters are eligible for the 23 mm SapienTM THV only. Despite the differences between the prostheses in terms of implantation technique, both of which required a specific learning period, the experience already acquired with the SapienTM THV led to a shortening of this period when the CoreValve® program was started in our centre. Other non-fatal complications were very rare. In particular, it should be noted that there was only one (1%) stroke leading to disabling sequellae, which seems quite unexpected in this aged and high-risk population undergoing retrograde cardiac catheterization with bulky devices. Furthermore, the risk of stroke in our study was comparable with previous surgical AVR series [18], despite our patients were at higher risk than patients selected for conventional surgical AVR. Nevertheless, the risk of stroke remains a major concern. To date, there is no convincing evidence that it can be significantly reduced by the transapical approach, as compared to the TF approach. The current development of lower-profile and smaller catheters may further reduce this risk in the near future. Early outcome Late outcomes Although predictive risk scores have limitations, with a trend towards risk overestimation in the most severe patients [15,16], the present 7% 30-day mortality clearly compares favourably with the 26% operative mortality predicted by the EuroSCORE and the 15% predicted by the STS score. It is similar to the mortality reported by Piazza et al. in a multicenter registry, using the CoreValve® System in 646 patients who, however, tended to have a lower risk profile (mean EuroSCORE 23%) [7], and it is lower than the 11% mortality reported by Grube et al. in a single-centre registry with the same device [6]. Our mortality is very similar to the one recently reported by Webb et al. in 113 patients treated via the TF approach with the SapienTM THV [11]. One-third (2/6) of early deaths occurred during the procedure itself, and all but one within the first 24 hours after performing the procedure. All deaths were due to cardiovascular causes, and specific analysis of each death suggested that most were linked to potential screening mistakes (e.g., aortic annular rupture, massive paravalvular leak after TAVI in a bicuspid valve), and possibly might have been avoided by experience. We already pointed out the major clinical impact of this learning curve [10], which is also shown by Webb et al. in their last series where 30-day mortality fell from 12.3% in the initial half of experience to 3.6% in the second half of experience [11]. The main cause of severe morbidity when using the SapienTM THV remained vascular complications, due to the large diameters of the sheaths. However, they were seldom life-threatening or led to secondary intervention, and were mainly associated with a high need for transfusions. As previously observed in a large series [7], this risk was reduced dramatically by the use of the CoreValve® System, compatible with 18 Fr sheaths. The second most frequent complication was represented by heart blocks necessitating pacemaker implantation. Despite a lack of statistical power, their frequency seemed, as previously observed, higher after CoreValve® System than after SapienTM THV implantation [6—7]. Reasons for the difference between both prostheses have been analysed [17]. Particular attention should be paid to the delay in occurrence of conduction defects, up to 4 days in the present series, implying a prolonged cardiac monitoring after the procedure for optimal safety. At follow-up with a median time of 9 months and a maximum of 3 years, mortality was due to non-cardiac causes in at least one-third of the patients. As observed by Webb et al. [11], the incidence of late adverse valve-related events was low. However, contrary to the latter, we did not observe severe gastrointestinal bleedings, which occurred in patients with combined dual antiplatelet and warfarin therapy. In those patients requiring long-term anti-thrombotic therapy, our practice was indeed to restrict antiplatelet therapy to either aspirin or clopidogrel. As reported previously [19], aortic regurgitations more than mild were rare but grade ≥II paravalvular leaks contributed, at least in part, to left ventricular failure and late fatal outcomes in two patients. Overall, the 1- and 2-year survival rates were consistent with those reported in the most recent TF series [11], and compared favourably with previous ones [6,20,21]. Most importantly, in this aged population, functional class improvement was dramatic and sustained after TAVI. While 98% of patients were in NYHA class III or IV before intervention, 82% of survivors were in class I or II at last follow-up. There was only one stroke leading to definitive sequellae in a patient who died from sepsis 3 months after intervention. In most cases, persistence of NYHA class IV symptoms was associated with concomitant severe pulmonary disease and in others to multifactorial systolic or diastolic left ventricular dysfunction. More accurate determination of clinical predictors of poor functional results of TAVI will be necessary to further improve the effectiveness of the screening process. Learning curve The direct impact on patients’ outcomes of a learning curve period has already been observed and discussed in series using the SapienTM prosthesis via a TF approach alone, or combined TF and transapical approaches [10,11,20]. The present study leads to the same conclusions. The comparison of the survival curves of the first and last patients shows that excess mortality in the former group occurs in the periprocedure period, with subsequently parallel curves, thus confirming the close influence of experience on patients’ immediate outcomes, via the screening process, the performance of the procedure and early postoperative care. Indeed, this learning curve involves not only the interventional cardiologists and cardiovascular surgeons in 244 charge of the procedure, but also imaging specialists, anaesthesiologists and all the members of the team participating in the TAVI programme. D. Attias et al. [3] Study limitations This study reflects a single-centre experience, with a learning period, and involving a limited number of patients. It also reflects the current results of the TF approach for TAVI, which may change in the near future due to the expected technological evolutions and greater experience. In the present study, the SapienTM THV was the only prosthesis available until May 2008, and since then, the CoreValve® System has been used in case of contraindications to the former. This strategy is somewhat arbitrary, but has increased the number of patients who could be treated by TF TAVI. No comparison between prostheses can be drawn from its results. Several other strategies may be interesting to further assess the respective places and results of the different approaches and prostheses available, e.g., using the CoreValve® System in all patients, or the transapical approach with the SapienTM THV in all patients, or combining the TF approach with the CoreValve® System and the transapical approach with the SapienTM THV. [4] [5] [6] [7] [8] Conclusion and future directions The availability of both SapienTM THV and CoreValve® System increases the number of patients who can be treated by TF TAVI. Immediate results are strongly related to both the quality of the screening and experience. Late functional and survival results are satisfactory and sustained. In the near future, expected technological improvements, with reduction of sheaths diameters, will allow routine performance of entirely percutaneous procedures under local anaesthesia, and then most probably further extend the place of the TF approach for TAVI, by increasing its feasibility, safety and overall clinical benefit. [9] [10] [11] [12] [13] Conflicts of interest statement [14] Dominique Himbert is proctor for Edwards Lifesciences; Bernard Iung received speaker’s fees from Edwards Lifesciences; Alec Vahanian is consultant for Edwards Lifesciences. References [1] Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: the euro heart survey on valvular heart disease. Eur Heart J 2003;24:1231—43. [2] Bonow RO, Carabello BA, Chatterjee K, et al. 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