Surgical aortic valve replacement (SAVR) is the primary treatment modality recommended for severe aortic stenosis. However, the need for a less-invasive, non-surgical treatment option for high-risk patients has recently culminated in development of transcatheter aortic valve implantation (TAVI). Currently, two devices are clinically in use. The Edwards Sapien valve is a bovine pericardium prosthesis mounted on a balloon-expandable stent that is placed in the subcoronary position. It can be placed by an antegrade (transapical) or retrograde (transfemoral) approach. The CoreValve transcatheter aortic valve is a self-expanding nitinol frame porcine pericardium prosthesis, placed by a retrograde (transfemoral or subclavian) approach. The second generation of Edwards prosthetic valve was named as Edwards XT, and its delivery system is smaller than that of Edwards Sapien. There are two types of delivery systems for Edwards Sapien prosthetic valves: 22 French and 24 French for 23-mm valve and 26-mm valve respectively. Similarly, there are two types of delivery systems for Edwards XT prosthetic valves: 16 French and 18 French for 23-mm valves and 26-mm valves respectively.1
The randomized trial PARTNER has confirmed the safety and efficiency of TAVI with Edwards prosthetic valves in high-risk patients or inoperable patients.2,3 However, the mortality and complication rate were still high, the acute result may be further improved with amelioration of devices and techniques, and accumulation of experiences. We reported the procedure results of 48 consecutive patients intended to undergo TAVI with Edwards prosthetic valve, and analyzed in detail the causes of 30-day mortality and clinical events in the transition time of old generation Edwards prosthetic valves to new generation valves.
This is a TAVI Registry of University Hospital of Caen, France. The Edwards prosthetic valves were solely used in this clinical trial. The first patient was enrolled in July 2010 and all consecutive TAVI procedures were included. Patient follow-up was obtained during and immediately after valve implantation, and at 30 days.
After evaluation by a heart team consisting of cardiologists, anesthesiologists and cardiac surgeons, patients with severe aortic valve stenosis requiring AVR were considered as TAVI candidates if they were at the “high” risk for surgical AVR, or if they were considered “inoperable”.
Pre-procedure screening and approaches choices
Pre-procedure screening comprised echocardiography, coronary angiography, aorto-angiography, ili-femoral angiography, and CT scan. The marked hypertrophy of the septum, atrial or ventricular thrombus, mitral regurgitation >grade 2, left ventricular ejection fraction <20%, were all exclusion criteria. The measurement of aortic annulus was performed with transthoracic echocardiography (TTE) and CT scan. The 23 mm and 26 mm Edwards prosthetic valves were respectively used for an annulus with a diameter of 18-21 mm and 22-24 mm.
The femoral approach is the first access choice for all TAVI candidates. The TAVI was conducted through apical approaches in the patients with following situations: diameter less than 8 mm (for old delivery system) or 6 mm (for new delivery system) in the iliac/femoral arteries; excessive angulations or calcification in iliac or femoral arteries; significant obstructive atherosclerotic disease; ulcerated plaques or dissections.
Categorical data are presented as frequencies and percentages; continuous variables are expressed as mean ± standard deviation. For 2-group comparisons, continuous variables were compared using either a 2-sample t test or a Mann-Whitney nonparametric test. The comparisons of categorical variables were made with the 2-sided chi-square test or, when appropriate, the 2-sided Fisher's exact test. Multivariable Logistic regression model was used to identify independent predictors of hospital mortality after TAVI. Variables exhibiting statistical significance in the univariate regression were then used in the multi-Logistic regression model. All statistical analyses were conducted with SPSS18.0 software package (SPSS Inc, Chicago, USA). A value of P <0.05 was considered statistically significant.
Forty-eight consecutive patients who underwent TAVI until September 2011 were enrolled in this registry. One patient who was planted for apical approach died during induction anesthesia. In fact, 28 patients were treated by transfemoral approach (TF), and 19 patients were treated by transapical approach (TA). This registry study was conducted in the transition time of old generation Edwards valve to new generation Edwards valve. The first 10 patients were implanted with Edwards Sapien prosthetic valves and the rest patients were implanted with Edwards XT. The baseline patients' characteristics are shown in Table 1. There were no significant differences between TF and TA in all these baseline parameters, though aortic valve area (AVA) had a trend to be smaller and atrial fibrillation had a trend to be more frequent in TF group than in TA group (P=0.067 and P=0.068).
Procedural results and 30-day follow-up
Device success, procedural success, procedural mortality and peri-procedure complications were reported on standardized endpoint definitions for TAVI.4
Twenty patients were in TA group and 28 in TF group among these 48 TAVI candidates. Device success rate was 95.8%, and procedural success rate was 93.7% in total. Procedural mortality was 6.7% (3/48): two deaths in TA group (10.0%), and one death in TF group (3.6%). Forty-six Edwards valves were implanted in total: 10 Edwards Sapien and 36 Edwards XT. Sixteen valves were in a size of 23 mm, and 30 valves in a size of 26 mm.
Peri-procedure complications were as follows: (1) Cardiac tamponade: two cases (4.2%), necessitating pericardiocentesis. (2) Peri-procedural MI: one case (2.1%). (3) Third degree atrioventricular block: three cases, one spontaneously recovered to sinus rhythm, one converted to atrial fibrillation, and one received permanent pacemaker (2.1%). (4) Bleeding: eight cases (16.7%), two life-threatening bleeding, one major bleeding, five minor bleeding. (5) Access site or access-related vascular injury: four cases (8.4%), one major vascular complication, three minor vascular complications. (6) Acute kidney injury (AKI) (modified RIFLE classification): four cases in AKI stage 3 (6.3%), one of them received renal replacement therapy (RRT). (6) Stroke: one minor stroke (2.1%).
The 30-day survival rate was 89.6%. All-cause mortality was 10.4% (5 deaths): four in TA group (20%) and one in TF group (3.6%). The pre-TAVI NYHA classifications were compared with those at 30-day follow-up after TAVI in 43 patients. The patients numbers in NYHA classifications 1, 2, 3 and 4 were respectively 0, 12, 27 and 4. The patients numbers in NYHA classifications 1, 2, 3 and 4 at 30 days after TAVI were respectively 10, 24, 9 and 0. The NYHA classifications were significantly improved after TAVI (P <0.001).
Mortality independent variables selection: the univariate regression
The independent variables selection was conducted through 28 variables (Tables 2 and 3). The results analyzed by single Logistic regression show that no variable was admitted into multivariate regression analysis.
The cause analysis of 30-day mortality
The causes of death for TA group are as follows: (1) Case one: cardiac arrest and died before TAVI procedure during the induction anesthesia (planted for apical approach). (2) Case two: hypotension and cardiogenic shock during the procedure, just after placement of the RetroFlex introducer sheath and before balloon aortic valvuloplasty (BAV); two BAVs were realized for emergency treatment, but not useful. The myocardial hematoma of left ventricle was one probable explanation. (3) Case three: Edwards aortic valve was deployed successfully in correct place. After suture of apical wound, there was bleeding surrounding the wound, which was successfully managed. Patient died due to hemorrhage several hours after the procedure. (4) Case four: died due to infection and multivisceral failure one week after the procedure.
The only death in TF group was due to right coronary occlusion and acute myocardial infarction 30 minutes after successful deployment of the Edwards prosthetic valve.
Traditionally surgical aortic valve replacement was standard therapy for patients with severe aortic stenosis. However, these patients were usually very older, and always co-morbid with several diseases, and some of them could not be operated because of “high risk or inoperable”.
Since the first-in man TAVI realized by Cribier et al in 2002,5,6 this technology has grown currently to become a true alternative to surgery in patients with severe aortic stenosis but rejected for surgery. Randomized Partner trial demonstrated that transfemoral aortic valve implantation was superior to medication therapy, and absolute mortality rate decreased 20% in “inoperable” patients; and in high surgical risk patients TAVI was not inferior to traditional surgical aortic valve replacement.2,3
However, the procedural mortality rate of TAVI was relatively high. The procedural mortality rate was 6.7%, and 30-day mortality rate was 10.4% in our registry study. This result was comparable to those reported by registry studies and randomized trial.2,3,7,8 In an effort to look for predictable factors of 30-day mortality, we did not find the same result as reported previously.9 The traditional risk factors (such as ages, EF, logistic Euroscore, AVA) did not predict the procedural and 30-day mortality in our study. Our sample was relatively small, and this statistical result may not reflect the true fact.
This prospective non randomized registry is one part of France 2 registry, and all consecutive cases were enrolled in the study. This result did not only reflect “leaning curve”, but also the improvement of device. The recent report from Vancouver analyzed the effect of the learning curve from the first 270 TVAI, and demonstrated that the overall procedure success rate improved (92.6% to 97.8%), and the overall 30-day mortality decreased (from 13.3% to 5.9%) with accumulation of experiences. Procedural experience (>135 procedures) was an independent predictor of 30-day survival.10 Our result reflected the real-world result during the “learning” period, and the procedural success and 30-day mortality were similar to those in the first stage of TAVI in Vancouver.
There are two approaches for TAVI with Edwards aortic valves. Tans-apical TAVI had a higher mortality than tans-femoral TAVI reported in some publications.2 The procedural and 30-day mortality had a trend to be higher in TA group than in TF group in our study but the difference did not reach statistically significant level. This is probably due to small sample.
In fact, there were two deaths for the first 10 TAVI, and there were 3 deaths for the rest 38 procedures. This trend perhaps reflects the change of device. Our registry study was performed in the transition time of old generation to new generation Edwards prosthetic valves. The first 10 cases were implanted with old generation Edwards aortic prosthetic valves: Edwards Sapien. The rest 36 prosthetic valves are Edwards XT. The femoral diameter compatible to old delivery system was at least 8 mm, and the blood vessel diameter compatible to new delivery system was at least 6 mm. Therefore, the percentage of femoral approaches was higher in the second part patients than in the first 10 patients. Access site or access-related vascular injury was dramaticly decreased with application of new generation of Edwards prosthetic valves.11
Procedure-related complications rate was acceptable. Stroke rate (2.1%) and permanent pacemaker implantation rate (2.1%) were especially low in this registry study.
The procedural success will be further improved, and the mortality of 30 days will decrease with the improvement of devices and accumulation of experiences.
In conclusion, the procedural success rate and 30-day mortality of the first 48 TAVI in the high surgical risk patients with Edwards prosthetic valves were acceptable.
Our registry represents the real-world results during one “learning” period and the transition time of old generation device to new generation device. The procedural and short-time results may be further improved with amelioration of device and accumulation of experience.
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