When aortic stenosis progresses to the point of symptoms,

Valvular Heart Disease Percutaneous Transarterial Aortic Valve Replacement in Selected High-Risk Patients With Aortic Stenosis John G. Webb, MD; Sanjeevan Pasupati, MBChB; Karin Humphries, PhD; Christopher Thompson, MD; Lukas Altwegg, MD; Robert Moss, MD; Ajay Sinhal, MD; Ronald G. Carere, MD; Brad Munt, MD; Donald Ricci, MD; Jian Ye, MD; Anson Cheung, MD; Sam V. Lichtenstein, MD, PhD Background Percutaneous aortic valve replacement represents an endovascular alternative to conventional open heart surgery without the need for sternotomy, aortotomy, or cardiopulmonary bypass. Methods and Results Transcatheter implantation of a balloon-expandable stent valve using a femoral arterial approach was attempted in 50 symptomatic patients with severe aortic stenosis in whom there was a consensus that the risks of conventional open heart surgery were very high. Valve implantation was successful in 86% of patients. Intraprocedural mortality was 2%. Discharge home occurred at a median of 5 days (interquartile range, 4 to 13). Mortality at 30 days was 12% in patients in whom the logistic European System for Cardiac Operative Risk Evaluation risk score was 28%. With experience, procedural success increased from 76% in the first 25 patients to 96% in the second 25 (P 0.10), and 30-day mortality fell from 16% to 8% (P 0.67). Successful valve replacement was associated with an increase in echocardiographic valve area from 0.6 0.2 to 1.7 0.4 cm 2. Mild paravalvular regurgitation was common but was well tolerated. After valve insertion, there was a significant improvement in left ventricular ejection fraction (P 0.0001), mitral regurgitation (P 0.01), and functional class (P 0.0001). Improvement was maintained at 1 year. Structural valve deterioration was not observed with a median follow-up of 359 days. Conclusion Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis. (Circulation. 2007;116:755-763.) When aortic stenosis progresses to the point of symptoms, the prognosis with medical management alone is poor. 1,2 Unfortunately, many patients with severe aortic stenosis do not undergo surgical aortic valve replacement (AVR), despite the proven benefits of this therapy. 2 7 Such patients frequently have comorbidities, in particular advanced age, that increase the morbidity and mortality associated with sternotomy, aortotomy, and cardiopulmonary bypass. 4,5 Clinical Perspective p 763 A percutaneous alternative was first explored in an animal model by Andersen et al. 8,9 Subsequently, a number of groups pursued various approaches to transcatheter aortic valve implantation. 8 16 It was not until a decade after initially proposed that the feasibility of percutaneous AVR was demonstrated in humans by Cribier et al 17,18 using a transvenous, transseptal approach. Subsequently, we described a retrograde procedure using percutaneous femoral artery access. 19 We report the early and late outcomes with this procedure in the initial 50 high-risk patients. Key Words: stenosis stents valves valvuloplasty Methods Patients Percutaneous AVR was approved for compassionate clinical use by the Department of Health and Welfare (Ottawa, Canada) in symptomatic patients not considered candidates for open heart surgery. A team of cardiologists and cardiac surgeons accepted patients on the basis of a consensus that conventional surgery was excessively high risk in terms of anticipated mortality and morbidity. Patient or physician preference alone was not considered adequate. 14 Written informed consent was obtained. Patients underwent coronary and aortofemoral angiography. The diameter of the aortic annulus was measured from the echocardiographic parasternal long-axis view at the level of the leaflet attachments. Patients were excluded if the aortic annulus diameter was 18 or 26 mm, if there was severe iliofemoral arterial disease, or if a reasonable quality or duration of life was considered unlikely despite valve replacement because of comorbidities. Prosthetic Valve Implantation Procedures were performed in a catheterization laboratory, usually under general anesthetic with endotracheal intubation. Patients were premedicated with aspirin, clopidogrel, and vancomycin. Heparin was used to maintain activated clotting time 250 seconds. Vaso- Received February 22, 2007; accepted June 1, 2007. From the Divisions of Cardiology and Cardiac Surgery, St Paul s Hospital and the Centre for Health Evaluation and Outcome Sciences, University of British Columbia, Vancouver, British Columbia, Canada. Correspondence to John Webb, MD, Director, Cardiac Catheterization, St. Paul s Hospital, 1081 Burrard St, Vancouver, BC, Canada V6Z 1Y6. E-mail webb@providencehealth.bc.ca 2007 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.107.698258 755

756 Circulation August 14, 2007 Figure 1. Left, Photograph of the balloon-expandable stent from the aortic aspect showing leaflets in the closed position (top) and from the side showing the fabric sealing cuff (bottom). Middle, Fluoroscopic image of the implanted and fully expanded valve as seen from the aortic aspect (top). The aortic angiogram (bottom) shows the valve securely fixed in the annulus. The left main coronary artery can be seen to originate from the sinotubular junction above the valve adjacent to a transesophageal echo probe. Right, Transesophageal echocardiogram short axis (top) and long axis (bottom). Ao indicates aorta; LA, left atrium; LVOT, left ventricular outflow tract; and SV, sinus of Valsalva. constrictor agents were used to maintain coronary perfusion pressure during periods of hemodynamic instability. Cardiopulmonary bypass was not used. A percutaneous sheath (22F or 24F) was placed in the femoral artery. The balloon-expandable prosthesis (Cribier Edwards, Edwards Lifesciences Inc, Irvine, Calif) is a tubular slotted stainless steel stent with an attached equine pericardial trileaflet valve and fabric sealing cuff (Figure 1). Two sizes were available: 23- and 26-mm expanded diameter. The prosthetic stent valve was mechanically crimped onto a balloon catheter immediately before implantation. With a steerable guiding catheter, the balloon-mounted valve was passed retrogradely through the aorta and positioned within the native aortic annulus as previously described. 19 Positioning was confirmed by fluoroscopy, aortography, and transesophageal echocardiographic imaging. 20 Transient partial cardiac standstill was induced with right ventricular burst pacing to minimize transvalvular flow and cardiac motion. 21 The delivery balloon was inflated to expand the valved stent, thereby excluding and compressing the native aortic valve. The femoral puncture site was closed surgically, followed by extubation in the catheterization laboratory and mobilization the next day. Aspirin was continued indefinitely; clopidogrel was continued for 1 to 3 months. Warfarin was substituted for clopidogrel in patients with atrial fibrillation. Data and Definitions Clinical follow-up and transthoracic echocardiograms were obtained before discharge and at 1, 6, and 12 months. Patients in whom the procedure was not successful were followed up for 30 days. Procedural success was defined as implantation of a functioning prosthetic valve within the aortic annulus and without in-laboratory mortality. Structural valve deterioration was defined as any change in valve function resulting from an intrinsic abnormality causing stenosis or regurgitation. 22 Myocardial infarction was defined as elevation of troponin T above normal with ECG evidence of ischemia and a compatible clinical history. Severe lung disease was defined as respiratory dysfunction impeding the patient s activity with a proven diagnosis of lung dysfunction on lung function test or diagnosed by a respiratory physician. Patients given bronchodilators but without proven lung disease were not included in this category. Echocardiographic aortic regurgitation severity was the consensus grade of 2 senior echocardiographers using the ratio of regurgitation jet to left ventricular outflow tract height and regurgitation pressure half-time determination. 23,24 Clinical follow-up was completed for all patients, and these data were used to plot survival. Echocardiograms were obtained in 98%, 100%, 86%, and 100% of patients reaching discharge and 1, 6, and 12 months, respectively. Statistical Analysis Categorical variables are presented as frequencies and continuous variables as means or medians as appropriate. Survival curves were generated with the Kaplan-Meier method (censored data). Survival rates in the first 25 patients and second 25 patients were compared by use of the log-rank test. Paired t test or Wilcoxon signed rank test was used for continuous variables, and the binomial test for ordinal variables was used to compare echocardiographic variables at baseline and after the procedure. The same parameters were evaluated for changes from postprocedure and 1, 6, and 12 months using a repeated-measures mixed model for continuous outcomes, and ordinal logistic regression, assuming proportional odds, was used for ordinal outcomes with adjustment for baseline values. General estimating equations (GEE) methodology was used to adjust for the correlation between multiple measurements from the same patient. A strength of the GEE methodology is that subjects contributed data up to their last scheduled visit. A 2-sided value of P 0.05 was considered statistically significant. All analyses were conducted with SPSS version 13.0 (SPSS Inc, Chicago, Ill) except for the time trend analyses, which were conducted with SAS version 9.1 (SAS Corp, Cary, NC). The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written. Results Patients Percutaneous transfemoral transarterial valve replacement was attempted in 50 high-risk severely symptomatic patients. Mean age was 82 7 years (range, 62 to 94 years). Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk score was 28%. 25,26 Comorbidities included, among others, coronary artery disease (72%), moderate to severe mitral regurgitation (48%), severe lung disease (32%), prior thoracotomy (34%), porcelain aorta (16%), severe pulmonary hypertension (18%), prior cerebral ischemic events (12%), and severe debility (22%). Baseline characteristics are shown in Table 1. Study flow is shown in Figure 2. Early Outcome Procedural success was achieved in 43 patients (86%). Valve implantation was unsuccessful in 7 attempts. Reasons for

Webb et al Percutaneous AVR 757 TABLE 1. Baseline Characteristics of 50 High-Risk Patients Undergoing Percutaneous AVR Characteristic Age, y, mean SD 82 7 Female sex 20 (40) New York Heart Association class I 0 (0) II 5 (10) III 32 (64) IV 13 (26) Body mass index 20 kg/m 2 4 (8) 20 24.9 kg/m 2 19 (38) 25 29.9 kg/m 2 16 (32) 30 kg/m 2 11 (22) Hypertension 31 (62) Diabetes 12 (24) Coronary artery disease 36 (72) Severe lung disease 16 (32) Cerebral ischemic event 6 (12) Peripheral vascular disease 10 (20) Prior thoracotomy 17 (34) Glomerular filtration rate 60 ml/min 26 (52) Ejection fraction 50% 12 (24) Mitral regurgitation (moderate or severe) 24 (48) Pulmonary hypertension 60 mm Hg 9 (18) Porcelain aorta 8 (16) Frail and poor mobility 11 (22) Predicted 30-d surgical mortality, mean %* 28 Values are expressed as n (%) unless otherwise noted. *Logistic EuroSCORE failure included inability to pass the iliac artery in 1 patient and cross the aortic valve in 3 patients, a defective prototype delivery catheter in 1 patient, and malpositioning in 2 patients. Malpositioning of the prosthesis occurred in 2 patients very early in the experience (patients 4 and 9). In both cases, the prosthesis was incorrectly expanded above the level of the aortic annulus so that it was free in the ascending aorta, although constrained by the delivery catheter. The valves were withdrawn with the delivery catheter and further dilated and fixed within the transverse aorta in a location where major branch vessels would not be compromised. Both procedures were otherwise uncomplicated. One patient subsequently underwent elective conventional AVR at 103 days. A second patient continues on medical management for aortic stenosis. Both patients remain alive at 12 months after their procedures. The initial 2 patients in the series (patients 1 and 2) suffered iliac injury requiring major vascular repair, with subsequent mortality in 1 patient. In a third patient, perforation of the abdominal aorta resulting in mortality occurred as a consequence of difficulty in advancing the bulky prosthesis across the stenotic aortic valve. A fourth patient with retroperitoneal bleeding from an iliac artery perforation was successfully treated with a covered stent. Two patients received antibiotics for access site infections after complex vascular closure. During the course of this experience, vascular access techniques, equipment, and screening evolved with a reduction in vascular complications. Periprocedural stroke occurred in 2 patients, with complete recovery in 1 patient and mortality at day 29 in the second. Median hospital stay was 5 days (interquartile range, 4 to 13). By 30 days after successful valve replacement, 50% of patients had improved by 1 New York Heart Association functional classes (P 0.0001). Outcome events are listed in Table 2. Mortality at 30 days was 12% in patients in whom the logistic EuroSCORE risk score was 28%. 25,26 There was 1 intraprocedural death caused by aortic injury (2%). The additional 5 postprocedural deaths occurring within 30 days of the procedure were a consequence of ventricular arrhythmia, left main occlusion, iliac injury, stroke, and multiorgan failure (each in 1 patient). No patient underwent conversion to open heart surgery within the initial 30-day follow up period. Late Outcome All procedures were done 6 months and 30 were done 1 year before last follow-up contact. There were 3 deaths occurring after 30 days (days 56, 71, and 98 as a result of respiratory failure, myocardial infarction, and renal failure, respectively) but no subsequent deaths. Of the successfully implanted patients, 35 and 17 patients were alive at 6 and 12 months, respectively (Figure 2). At a median follow-up of 359 days (interquartile range, 60 to 371 days), 35 of 43 patients undergoing successful transcatheter AVR (81%) remained alive. Figure 3A illustrates the Kaplan-Meier survival after percutaneous valve implantation. Subsequent valve procedures were performed in 3 patients. In each case, the reason was ongoing symptomatic aortic stenosis after an unsuccessful transcatheter procedure. Repeat valve procedures consisted of transcatheter AVR using direct left ventricular apical puncture at day 11, conventional surgical AVR at day 103 (as discussed above), and reattempted transfemoral transcatheter AVR at day 466. All 3 procedures were successful with all 3 patients remaining alive at the 30-day follow-up. Structural valve deterioration was not observed during follow-up. The early improvement in functional class achieved after valve insertion was maintained at 6 months and 1 year (P 0.59, GEE for time trend) (Figure 4E). Learning Curve Characteristics and outcomes in the initial 25 patients and subsequent 25 patients were compared. Baseline characteristics were not significantly different with respective mean ages of 82 7 versus 82 8 years. However, rates of procedural success, malposition, and intraprocedural and periprocedural mortality were more favorable in the later group. Procedural success increased from 76% to 96% (P 0.10), malposition fell from 8% to 0%, and intraprocedural mortality fell from 4% to 0%. Logistic EuroSCORE 25,26 operative mortality

758 Circulation August 14, 2007 estimation was 26% in the initial cohort and 30% in the later cohort. Actual 30-day mortality was 16% in the initial cohort, falling to 8% in the later cohort (P 0.39). Survival at 0, 1, and 6 months in the early and late cohorts was 96%, 84%, and 70% in the initial cohort and 100%, 92%, and 88% in the later cohort as illustrated in Figure 3B (P 0.09). There were no deaths between 6 and 12 months. Echocardiographic Evaluation Transthoracic echocardiography documented an immediate reduction in transaortic mean gradient from 46 17 to 11 5 mmhg(p 0.001) and an increase in estimated aortic valve area from 0.6 0.2 to 1.7 0.4 cm 2 (P 0.0001). Time trend using the multiple linear regression models showed this improvement to be maintained up to 1 year (Figure 4A). Echocardiography documented prosthetic valve durability with no structural or significant hemodynamic deterioration at a median follow-up of 359 days extending to a maximum follow-up of 734 days. Left ventricular ejection fraction increased after AVR from a mean of 53 15% to 57 13% (P 0.0001) within days. This improvement in ejection fraction was sustained up to 1 Figure 2. Diagram illustrating study flow. BEAV indicates balloon-expandable aortic valve; SVD, structural valve deterioration. year (P 0.80, GEE for time trend). For the most part, this increase was due to an improvement in patients with moderate to severe left ventricular dysfunction. A left ventricular ejection fraction 40% at baseline was documented in 21% of patients before successful valve implantation, falling to 12%, 13%, 0%, and 6% at discharge and 1, 6, and 12 months, respectively (Figure 4B). Figure 5A shows the time trend in left ventricular ejection fraction in the 30 patients in whom left ventricular function was assessed at 6 months. This shows a trend to further improvement in ejection fraction after the time of discharge not resulting from patient selection, although this trend was not significant on the basis of GEE evaluation for time trend. Mitral regurgitation grade decreased from a median grade 2 (moderate) to grade 1 (mild) at discharge (P 0.01). Moderate to severe mitral regurgitation at baseline was present in 53% of successfully implanted patients, falling to 33%, 31%, 25%, and 24% at discharge and 1, 6, and 12 months, respectively (Figure 4C). The improvement in mitral regurgitation after valve insertion was maintained up to 1 year (P 0.52, GEE for time trend). Figure 5B examines the 29 patients who had mitral regurgitation assessed at 6 months.

Webb et al Percutaneous AVR 759 TABLE 2. Outcome After Percutaneous AVR in 50 High-Risk Patients Characteristic Procedural success 43 (86) Stroke 2 (4) Myocardial infarction 1 (2) Ventricular fibrillation 2 (4) Heart block, new and sustained 2 (4) Tamponade* 1 (2) Transfusion 3 U 9 (18) Emergent cardiac surgery 0 (0) Endocarditis 0 (0) Death, intraprocedural 1 (2) Death, 30 d 6 (12) Death, stroke, or myocardial infarction at 30 d 8 (16) Values are expressed as n (%). *Complication of postprocedural implantation of a permanent pacemaker. There was a trend toward ongoing improvement in mitral regurgitation up to 6 months. Most of this improvement occurred in patients with moderate or severe mitral regurgitation. Most patients had some degree of aortic insufficiency at baseline (Figure 4D). After AVR, aortic regurgitation increased from a median grade 0 (none/trivial) to grade 1 (mild) (P 0.57) as determined by transthoracic echocardiography. Aortic regurgitation grade after valve implantation was unchanged in 24%, worsened in 44%, and improved in 32%. Postprocedural aortic insufficiency was determined by transesophageal echocardiography to be valvular (through the valve) or paravalvular (around the valve). In no patient was prosthetic valvular insufficiency more than mild. Most patients did have some degree of paravalvular insufficiency. When paravalvular insufficiency was judged excessive by transesophageal echocardiography, the prosthesis was sometimes redilated at the discretion of the operator, often with the addition of a very small amount of fluid to the semicompliant valvuloplasty balloon to achieve more complete and symmetrical expansion of the valve. Cautious redilation was not observed to result in leaflet damage or displacement of the prosthetic valve. No patient was left with severe paravalvular insufficiency. Moderate paravalvular insufficiency was observed in 3 patients, all of whom remained stable at followup. Clinical hemolysis was not observed. Discussion Mortality Risk Prognosis in patients with symptomatic aortic stenosis is poor, 2,27 and surgical AVR can be performed in good candidates at very low risk. 7 However, large surgical series report a 5% to 15% operative mortality for isolated AVR in patients 70 years of age, 27 and benchmark Medicare data document an operative mortality of 8.8% for patients 65 years of age. 28 Surgical mortality rates escalate in the presence of comorbidities or the need for additional cardiac procedures. 27,29 34 The factors that have a major impact on the risk of thoracotomy, aortotomy, or cardiopulmonary bypass (such as porcelain aorta, lung disease, or debility) may differ from those factors that determine the risk associated with a transarterial procedure such as iliofemoral disease. Better understanding of the risks associated with transcatheter procedures may allow improved patient selection. Our experience suggests that percutaneous AVR can be performed with a mortality that compares favorably with that of open heart surgery in selected high-risk patients. Intraprocedural mortality was 2%, and 30-day mortality was 12%. In the latter half of this first-in-man percutaneous retrograde transarterial balloon-expandable valve experience, 30-day Figure 3. Kaplan-Meier survival. A, First consecutive 50 transarterial AVR patients. Logistic EuroSCORE mortality estimate was 28%. B, First 25 patients vs second 25 patients. Logistic EuroSCORE estimates were 26% and 30%, respectively.

760 Circulation August 14, 2007 Figure 4. Follow-up of functional class and echocardiographic parameters. A, Time trends in aortic valve area and aortic valve mean gradient (error bars indicate 1 SD). B, Time trend in left ventricular ejection fraction (EF). C, Time trend in mitral regurgitation. D, Time trend in aortic regurgitation. E, New York Heart Association functional class in patients who reached the 1-month follow-up.

Webb et al Percutaneous AVR 761 Figure 5. Left ventricular ejection fraction (EF) and mitral regurgitation trends in patients who completed the 6-month echocardiographic assessment. mortality fell further to 8% compared with a logistic Euro- SCORE of 30%. Admittedly, the accuracy of this and other available objective predictors of surgical mortality is controversial, sometimes underestimating risk but perhaps more commonly overestimating risk. 14,25,35,36 However, patients in the present series also were considered excessively high risk for surgery according to a consensus of senior surgeons and cardiologists representative of clinical practice in a highvolume center. It seems likely that with further incremental improvements in patient selection, techniques, and equipment, mortality rates with transcatheter valve implantation can decline further. Morbidity As important as mortality risk may be, procedural morbidity may weigh as heavily in the decisions made by elderly patients and their physicians. 37 Hospital stay in this percutaneous high-risk group of largely elderly patients was relatively short at a median of 5 days and as little as 2 days. Although morbidity is difficult to further quantify, a procedural stroke rate of 4% and a sustained improvement in functional class are encouraging. Learning Curve Femoral transarterial valve implantation shares much in common with other percutaneous cardiac procedures. 19 Nevertheless, a learning curve was apparent, likely attributable to incremental improvements in technique, equipment, and patient selection. Procedural success increased from 76% in the first half of this experience to 96% in the latter half. Malposition occurred very early in the experience and did not recur later in this experience as a consequence of improvements in understanding of the requirements of accurate positioning at the time of deployment and improvements in imaging. Major arterial complications declined with improvements in sheaths, angiographic screening, and technique. Left main occlusion, which occurred early in the experience, has not recurred after the application of routine fluoroscopic, angiographic, and echocardiographic screening for the presence of excessively bulky aortic valve leaflets, although the potential for it requires further study. Valve and Cardiac Function A prosthetic valve area of 1.7 cm 2 compares favorably with currently available surgical valves. Neither structural valve deterioration nor inadequate fixation of the prosthesis was observed at a mean follow-up of almost 1 year or in individual patients out to 2 years. Paravalvular insufficiency was common but generally mild, stable, and less of a concern than anticipated. 18 However, paravalvular insufficiency does remain a concern, and further evaluation, including the potential for low-grade hemolysis and other hematological abnormalities, is required. 38,39 In the present series, 48% of patients had moderate to severe mitral regurgitation, and 72% had coronary disease possibly sufficient to warrant the additional potential increased mortality risk with mitral valve replacement or coronary bypass had these patients undergone conventional AVR. 27,29 33 Mitral regurgitation and coronary disease were generally well tolerated in these mostly elderly patients once aortic stenosis was relieved. Successful percutaneous aortic valve implantation was associated with a significant improvement in left ventricular function, mitral regurgitation, and functional class. Improvements were sustained at 1 year. Importantly, lack of late valve failure during clinical and serial echocardiographic with a median follow-up of almost 1 year suggests durability sufficient to offer significant benefit. Study Limitations Contraindications specific to transcatheter aortic valve implantation include an annulus too small or too large to accommodate the currently available prostheses or a partic-

762 Circulation August 14, 2007 ularly bulky aortic valve so that the prosthetic valve might displace an enlarged leaflet and obstruct a coronary ostium. Left ventricular dysfunction with nonrevascularized coronary disease and the potential for global ischemia during the procedure are relative contraindications. Arterial disease severe enough to prevent safe introduction of the prosthesis is a contraindication to a transarterial procedure. Vascular access injury, atheroembolism, and paravalvular insufficiency remain concerns and require further improvements in equipment and technique. In vivo durability of transcatheter valves equivalent to conventional surgical valves remains to be demonstrated. The presence of a learning curve requires careful dissemination of knowledge gained during development of this procedure. Early favorable experience with percutaneous AVR will need to be cautiously replicated in other centers, with larger numbers of patients, longer followup, and randomized evaluation. Conclusions Conventional open heart surgery remains first-line therapy for symptomatic aortic stenosis. However, percutaneous valve replacement is a viable alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis. Disclosures Drs Munt and Webb are consultants to Edwards Lifesciences Inc. The remaining authors report no conflicts. References 1. Vahanian A, Baumgartner H, Bax J, Butchart E, Dion RFG, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Ostersprey A, Tamargo J, Zamorano JL, Angelini A, Antunes M, Fernandez MA, Gohlke-Baerwolf C, Habib G, McMurray J, Otto C, Pierard L, Pomar JL, Prendergast B, Rosenhek R, Uva MS, Tamargo J. Guidelines on the management of valvular heart disease: the Task Force on the Management of Valvular Disease of the European Society of Cardiology. Circulation. 1998;28: 230 268. 2. Bonow RO, Carabello BA, Kanu C, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O Gara PT, O Rourke RA, Otto CM, Shah PM, Shanewise JS, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2006;114: e84 e231. 3. Varadarajan P, Kapoor N, Bansal R, Pai R. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg. 2006;82:2111 2115. 4. Bramstedt KA. Aortic valve replacement in the elderly: frequently indicated yet frequently denied. Gerontology. 2003;49:46 49. 5. Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Barwolf C, Levang OW, Tornos P, Vanoverschelde JL, Vermeer F, Boersma E, Ravaud P, Vahanian A. A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Valve Survey on Valvular Disease. Eur Heart J. 2003;24:1231 1243. 6. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez- Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368:1005 1011. 7. Charlson E, Legedza ATR, Hamel MB. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis. 2006;15: 312 321. 8. Andersen HR, Knudsen LL, Hasenkam JM. Transluminal implantation of artificial heart valves: description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs. Eur Heart J. 1992;13:704 708. 9. Andersen HR. Transluminal catheter implanted prosthetic heart valves. Int J Angio. 1998;7:102 106. 10. Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, Derumeaux G, Anselme F, Laborde F, MB L. Trans-catheter implantation of balloon-expandable prosthetic heart valves: early results in an animal model. Circulation. 2001;104(suppl II):I-552. 11. Sochman J, Peregrin JH, Pavcnik D, Timmermans H, Rosch J. Percutaneous transcatheter aortic disc valve prosthesis implantation: a feasibility study. Cardiovasc Intervent Radiol. 2000;23:384 388. 12. Lutter G, Kuklinski D, Berg G, Von Samson P, Martin J, Handke M, Uhrmeister P, Beyersdorf F. Percutaneous aortic valve replacement: an experimental study. J Thorac Cardiovasc Surg. 2002;123:768 776. 13. Bonhoeffer P, Boudjemline Y, Qureshi SA, Le Bidois J, Iserin L, Acar P, Merckx J, Kachaner J, Sidi D. Percutaneous insertion of the pulmonary valve. J Am Coll Cardiol. 2002;39:1664 1669. 14. Vassiliades TA Jr, Block PC, Cohn LH, Adams DH, Borer JS, Feldman T, Holmes DR, Laskey WK, Lytle BW, Mack MJ, Williams DO. The clinical development of percutaneous heart valve technology: a position statement of the Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery (AATS), and the Society for Cardiovascular Angiography and Interventions (SCAI) endorsed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA). J Am Coll Cardiol. 2005;45:1554 1560. 15. Boudjemline Y, Bonhoeffer P. Steps toward percutaneous aortic valve replacement. Circulation. 2002;105:775 778. 16. Webb JG, Munt B, Makkar RR, Naqvi TZ, Dang N. Percutaneous stentmounted valve for treatment of aortic or pulmonary valve disease. Catheter Cardiovasc Interv. 2004;63:89 93. 17. Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, Derumeaux G, Anselme F, Laborde F, Leon MB. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106:3006 3008. 18. Cribier A, Eltchaninoff H, Tron C, Bauer F, Agatiello C, Sebagh L, Bash A, Nusimovici D, Litzler PY, Bessou JP, Leon MR. Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol. 2004;43:698 703. 19. Webb JG, Chandavimol M, Thompson CR, Ricci DR, Carere RG, Munt BI, Buller CE, Pasupati S, Lichtenstein S. Percutaneous aortic valve implantation retrograde from the femoral artery. Circulation. 2006;113: 842 850. 20. Munt B, Webb J. Percutaneous valve repair and replacement techniques. Heart. Oct 2006;92:1369 1372. 21. Webb JG, Pasupati S, Achtem L, Thompson CR. Rapid pacing to facilitate transcatheter prosthetic heart valve implantation. Catheter Cardiovasc Interv. 2006;68:199 204. 22. Edmunds LH, Clark RE, Cohn LH, Miller C, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ann Thorac Surg. 1988;46:257 259. 23. Perry GJ, Helmcke F, Nanda NC, Byard C, Soto B. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol. 1987; 9:952 959. 24. Teague SM, Heinsimer JA, Anderson JL, Sublett K, Olson EG, Voyles WF. Quantification of aortic regurgitation utilizing continuous wave Doppler ultrasound. J Am Coll Cardiol. 1986;8:592 599. 25. Nashef SA, Roques F, Hammill BG, Peterson ED, Michel P, Grover FL, Wyse RK, Ferguson T. Validation of European System for Cardiac Operative Risk Evaluation (EuroSCORE) in North American cardiac surgery. Eur J Cardiothorac Surg. 2002;22:101 105. 26. Nilsson J, Algotsson L, Hoglund P, Luhrs C, Brandt J. Early mortality in coronary bypass surgery: the EuroSCORE versus the Society of Thoracic Surgeons risk algorithm. Ann Thorac Surg. 2004;77:1235 1239. 27. Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Guidelines on the management of valvular heart disease. Eur Heart J. 2007;428:e1 e39. 28. Goodney PP, O Connor GT, Wennberg DE, Birkmeyer JD. Do hospitals with low mortality rates in coronary artery bypass also perform well in valve replacement? Ann Thorac Surg. 2003;76:1131 1136. 29. Alexander KP, Anstrom KJ, Muhlbaier LH, Grosswald RD, Smith PK, Jones RH, Peterson ED. Outcomes of cardiac surgery in patients 80 years: results from the National Cardiovascular Network. J Am Coll Cardiol. 2000;35:731 738.

Webb et al Percutaneous AVR 763 30. Asimakopoulos G, Edwards MB, Taylor KM. Aortic valve replacement in patients 80 years of age and older: survival and cause of death based on 1100 cases: collective results from the UK Heart Valve Registry. Circulation. 1997;96:3403 3408. 31. Dalrymple-Hay MJ, Alzetani A, Aboel-Nazar S, Haw M, Livesey S, Monro J. Cardiac surgery in the elderly. Eur J Cardiothorac Surg. 1999;15:61 66. 32. Kolh P, Kerzmann A, Lahaye L, Gerard P, Limet R. Cardiac surgery in octogenarians: peri-operative outcome and long-term results. Eur Heart J. 2001;22:1235 1243. 33. Langanay T, De Latour B, Ligier K, Derieux T, Agnino A, Verhoye JP, Corbineau H, Chaperon J, Leguerrier A. Surgery for aortic stenosis in octogenarians: influence of coronary disease and other comorbidities on hospital mortality. J Heart Valve Dis. 2004;13:545 552. 34. Suttie SA, Jamieson WR, Burr LH, Germann E. Elderly valve replacement with bioprostheses and mechanical prostheses: comparison by composites of complications. J Cardiovasc Surg (Torino). 2006;47:191 199. 35. Fuster V, Goldbarg SH, Hansalia RJ, Stevens GR, Tiyyagura SR. The inoperable valvular heart disease patient: the pluses and minuses of percutaneous valvular replacement. Eurointervention. 2006;2:154 160. 36. Roques F, Nashef SA, Michel P, for the EuroSCORE Study Group. Risk factors for early mortality after valve surgery in Europe in the 1990 s: lessons from the EuroSCORE pilot program. J Heart Valve Dis. 2001; 10:572 578. 37. Mazur DJ, Hickam DH, Mazur MD. The role of doctor s opinion in shared decision making: what does shared decision making really mean when considering invasive medical procedures? Health Expect. 2005;8: 97 102. 38. Pate GE, Chandavimol M, Naiman SC, Webb JG. Heyde s syndrome: a review. J Heart Valve Dis. 2004;13:701 712. 39. Ionescu A, Fraser AG, Butchart EG. Prevalence and clinical significance of incidental paraprosthetic valvar regurgitation: a prospective study using transesophageal echocardiography. Heart. 2003;89:1316 1321. CLINICAL PERSPECTIVE Transcatheter aortic valve replacement represents an endovascular alternative to conventional open heart surgery without the need for sternotomy, aortotomy, or cardiopulmonary bypass. Percutaneous implantation of a balloon-expandable stent valve using a femoral arterial approach was attempted in 50 high-risk patients with severe symptomatic aortic stenosis. Mortality at 30 days was 12% in patients in whom the logistic European System for Cardiac Operative Risk Evaluation risk estimate was 28%. With experience, procedural success increased from 76% in the first 25 patients to 96% in the second 25, and 30-day mortality fell from 16% to 8%. After valve insertion, there was a significant improvement in left ventricular ejection fraction, mitral regurgitation, and functional class. Clinical improvement and valve function were maintained at 1 year. Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe aortic stenosis.

Percutaneous Transarterial Aortic Valve Replacement in Selected High-Risk Patients With Aortic Stenosis John G. Webb, Sanjeevan Pasupati, Karin Humphries, Christopher Thompson, Lukas Altwegg, Robert Moss, Ajay Sinhal, Ronald G. Carere, Brad Munt, Donald Ricci, Jian Ye, Anson Cheung and Sam V. Lichtenstein Circulation. 2007;116:755-763; originally published online July 23, 2007; doi: 10.1161/CIRCULATIONAHA.107.698258 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright 2007 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/116/7/755 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/