Mitroflow Aortic Bioprosthesis 5-Year Follow-Up: North American Prospective Multicenter Study

Transcription

1 Mitroflow Aortic Bioprosthesis 5-Year Follow-Up: North American Prospective Multicenter Study Federico M. Asch, MD, David Heimansohn, MD, Daniel Doyle, MD, Walter Dembitsky, MD, Francis D. Ferdinand, MD, Jeffrey Swanson, MD, Joseph A. Dearani, MD, and Neil J. Weissman, MD Medstar Health Research Institute at Medstar Washington Hospital Center, Georgetown University School of Medicine, Washington, DC; St. Vincent Heart Center of Indiana, Indianapolis, Indiana; Hospital Laval, Quebec City, Quebec, Canada; Sharp Memorial Hospital, San Diego Cardiac Center, San Diego, California; Lankenau Medical Center, Wynnewood, Pennsylvania; Providence St. Vincent Hospital, Portland, Oregon; Mayo Clinic/St. Mary s Hospital, Rochester, Minnesota Background. The Mitroflow valve (Sorin Group, Milan, Italy) has been in use since 1982 and has shown longterm durability in large studies from European centers but has not been studied for long-term hemodynamics in large standardized multicenter trials. This study sought to assess the hemodynamics of the Mitroflow valve by extending the duration of follow-up in an ongoing prospective multicenter trial conducted in North America. Methods. Six sites participated in this midterm study requiring annual follow-up and echocardiographic evaluation using a standardized transthoracic echocardiography acquisition protocol. Results. There were 276 patients enrolled (age 74 8 years) and 54% were in New York Heart Association (NYHA) functional class III-IV. Follow-up from the time of valve implantation had a mean of years with a cumulative follow-up of 1,102 patient-years. At 5 years of follow-up, 99% of patients were free of moderate or severe aortic regurgitation and 94% were in NYHA functional class I or II. Between baseline and 5 years, mean gradients increased an average of 0.4 to 4.3 mm Hg. The change in effective orifice area was appreciably small ( 0.1 to 0.3 cm 2 ) after 5 years. There were 57 deaths (4 early and 53 late) and 9 valve explants. Conclusions. The Mitroflow valve implanted in the aortic position has shown to be hemodynamically stable over a 5-year follow-up in an elderly population with a high prevalence of comorbid conditions. (Ann Thorac Surg 2012;94: ) 2012 by The Society of Thoracic Surgeons Bioprosthetic aortic valves have experienced increased use throughout North America because of optimal hemodynamics and reduced complication rates. In general, the current generation of pericardial valves has demonstrated increased durability over earlier versions. The Mitroflow pericardial valve has been in use in Europe since 1982 and became available in the United States in It is constructed from glutaraldehyde-fixed bovine pericardium sutured onto a flexible acetyl homopolymer stent covered with polyester cloth. A single piece of bovine pericardium, placed on the outside of the stent, forms the Mitroflow valve leaflets. The sewing ring is composed of a tungsten-impregnated silicone elastomeric insert for radiographic opacity. Favorable longterm durability has been demonstrated in large retrospective analyses from several European centers [1 8]. In addition, several previous retrospective and prospective studies have assessed the early valve hemodynamics of the Mitroflow valve [7 11] and other pericardial valves [12 16]. This study sought to assess the midterm hemodynamics of the Mitroflow valve by Accepted for publication April 26, Address correspondence to Dr Asch, MedStar Health Research Institute at Medstar Washington Hospital Center, Georgetown University, 100 Irving St NW, Ste EB5123, Washington, DC 20010; federico.asch@medstar.net. extending the duration of follow-up in an ongoing, rigorous prospective multicenter trial conducted in North America. Material and Methods The Mitroflow aortic pericardial prosthesis was studied in a North American prospective multicenter trial in 28 sites. That trial was conducted between November 2003 and December 2007 and followed the patients to assess hemodynamics and clinical outcomes [11]. Six sites with high enrollment and high degree of protocol compliance agreed to continue annual follow-up and echocardiographic evaluations. All patients from these sites are included in the current report. The closing date for follow-up and data entry in the current report was September Institutional review board approval was obtained from each site, and all patients gave informed consent to participate in the study extension. Drs Asch and Weissman disclose that they have financial relationships with Sorin Group, Medtronic Inc, St Jude Medical, Edwards Lifesciences, ATS Medical, Direct Flow Medical, Symetis Corp, Abbot Vascular, Mitralign, and Recor Medical; and Dr Dembitsky with Thoratec Corp and Triflo Medical by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 Ann Thorac Surg ASCH ET AL 2012;94: MITROFLOW AORTIC BOVINE BIOPROSTHESIS 1199 Echocardiographic Evaluation Transthoracic echocardiograms were obtained using a standardized acquisition protocol by trained, experienced sonographers. All echocardiograms were interpreted by a central laboratory following the American Society of Echocardiography guidelines and recommendations [17 22]. Standard prosthetic valve measurements were performed including mean and peak gradients, effective orifice area (EOA) and cardiac output. Left ventricular (LV) volumes and mass were measured according to the American Society of Echocardiography guidelines [23]. All the echocardiograms were interpreted by 1 board-certified echocardiologist (NJW) at a central core laboratory (Medstar Health Research Institute, Washington, DC). Clinical Evaluation Follow-up data, including adverse events, were collected primarily at office visits. In a few cases, follow-up was obtained by telephone if the patient had no adverse events and was not scheduled for an echocardiographic examination. Data were collected on all deaths, valve reoperations, and valve-related adverse events, including structural valve deterioration, thromboembolism, valve thrombosis, endocarditis, and perivalvular leaks. Documents from the medical records (eg, laboratory tests, operative reports, and hospital summaries) for each adverse event were reviewed and reported as defined by the Society of Thoracic Surgeons guidelines [24]. Statistical Analysis Mean standard deviation (SD) is presented for all continuous measurements. Mixed-model repeatedmeasures analysis of variance was used to model regression of echocardiographic measurements over time. Echocardiographic variables (mean gradient, peak gradient, EOA, LV mass) were tested for extreme skewness, and in each case a logarithmic transformation was applied to achieve a more normal distribution. After analyzing trends over time, the mixed-model analysis of variance was applied to the differences (deltas) at each period versus discharge (baseline), and paired comparisons were performed of the change in echocardiographic measurements (mean gradient, peak gradient, EOA) at 5 years versus baseline for each valve size. We also used this approach to perform paired comparisons of LV mass regression (deltas) at each postoperative period versus baseline. Hazard rates and Kaplan-Meier estimates with 95% confidence intervals were used to summarize patient survival and freedom from first event. All statistical analyses were performed using SAS statistical analysis software (SAS Institute, Cary, NC). p values 0.05 were considered statistically significant. All the data were stored by the sponsor in a central database. The echocardiographic data was also stored in the echocardiography core lab. Three statisticians had access to the data and performed the analysis 1 external, 1 from the echocardiography core laboratory, and 1 from the sponsor. The authors had unrestricted access to the data. Table 1. Preoperative and Surgical Characteristics Patients, N 276 Mean age (y) SD (range) (33 91) Female, N (%) 123 (44.6%) Concomitant procedures performed, N (%) 203 (73.6) Coronary artery bypass grafting 148 (53.6%) Ablation/Maze procedure 30 (10.9%) Mitral/tricuspid valve repair 24 (8.7%) Ascending aorta repair 14 (5.1%) Patients may have had multiple concomitant surgical procedures. Results There were 276 patients at the 6 sites and all were included in this analysis. A summary of patient and surgical characteristics is provided in Table 1. Of note, this cohort is similar to the patients previously reported in all 28 clinical sites [11]; this was an elderly population with high prevalence of comorbidities. The mean age was 73 years and 54% were in NYHA class III or IV. Follow-up from valve implantation had a mean of years (range, years) and a cumulative follow-up of 1,102 patient-years. All echocardiographic and clinical data acquired at the clinical sites for each of these patients since valve operations were included in the analysis. Among the 276 patients, there were 57 deaths (4 early deaths and 53 late deaths). There were 11 valve-related deaths and 24 cardiac-related deaths. Valve-related deaths were all late events ( 30 days after implantation) and were due to endocarditis (n 6), gastrointestinal (n 2) and cerebral bleeding (n 1), stroke (n 1), and structural valve dysfunction (n 1). There were 9 valve explantations. Forty-three patients withdrew from the study by request. Six patients were lost to follow-up (97.8% follow-up rate). Hemodynamic Results The baseline (hospital discharge after aortic valve replacement) mean and peak gradient and EOA and their change between baseline and 5years are presented in Table 2 for each valve size. As expected, the mean and peak gradients were higher in smaller-sized valves. In addition to valve size, mean gradient tended to be higher in older patients (p 0.001) and decreased with larger body surface area (p 0.001). There was also a significant interaction between valve size and time since surgical implantation (p 0.04), indicating that the trend in mean gradient over the age of the valve was significantly different among valve sizes. In the smaller-sized valves, the trend of increasing gradient over time appears to be most pronounced. However the relative changes in gradient at 5 years were not clinically relevant (Table 2). EOA increased with larger valve sizes. EOA was also higher in male patients (p 0.005). As with mean gradient, there was also a significant interaction between valve size and the time the valve was implanted (p 0.03). EOA appeared to decrease with time, and the trend was more prevalent in smaller valves. How-

3 1200 ASCH ET AL Ann Thorac Surg MITROFLOW AORTIC BOVINE BIOPROSTHESIS 2012;94: Table 2. Hemodynamics of the Mitroflow Aortic Pericardial Valve: Baseline Characteristics and Changes Over Time Measurement Valve Size Baseline 5 Years Mean at 5 Years a 95% CI p Value b Mean gradient , , , , , Peak gradient , , , , , EOA , , , , , a Mean of paired differences in mean gradient and EOA between 5 years and baseline (discharge) echocardiographic evaluations. of mean difference 0. b p value for test The number of patients who received each valve size was 6, 85, 90, 73, and 19 for sizes 19, 21, 23, 25, and 27 mm, respectively. Only 3 patients received the 29-mm valve; therefore the hemodynamic statistics for this size are not reported. CI confidence interval; EOA effective orifice area. ever the relative change in EOA after 5 years, ranging from 0.1 to 0.3 cm 2, is not considered clinically significant (Table 2). The LV mass decreased over time (p 0.001). Despite a slight increase from year 3 to year 5 (Fig 1), LV mass regression was significant (p 0.001) at all follow-up periods compared with baseline. Table 3 summarizes the aortic regurgitation (AR) findings for each valve size over time. Almost all patients (99%) were free of significant AR (moderate or severe) at the 5-year follow-up. Clinical Events A summary of clinical events is presented in Table 4. Overall survival was 89.8% at 1 year and declined to 84.5% and 77.1% at 3 and 5 years, respectively. Valverelated survival was 96.9%, 96.9%, and 95.3% at 1, 3, and 5 years, respectively. Cardiac-related survival was 93.7%, 92.9%, and 90.1% at 1, 3, and 5 years, respectively. Nine valves were explanted in this cohort; 2 for endocarditis, 6 for structural valve deterioration, and 1 for patient-prosthesis mismatch. Freedom from explantation was 99.2%, 98.8%, and 97.1% at 1, 3, and 5 years, respectively. Pathologic reports of the 6 valves explanted for prosthesis deterioration (mean of 50.4 months, range 32 65) determined that 4 were removed for calcific degeneration and 2 were removed for AR (a flail and a tear). The occurrence of valve-related adverse events is detailed in Table 4. Freedom from each of these events remained low and remarkably constant over the entire 5 years of study. The symptomatic improvement, as assessed by NYHA classification, was dramatic at each time point of follow- Table 3. Aortic Valvular Regurgitation Regurgitation Severity Discharge (n 269) 1 Year (n 241) 5 Year (n 153) % % % Fig 1. Left ventricular (LV) mass regression 5 years after implantation of the Mitroflow valve. Plots (median, 25th, 75th percentiles, and range) by follow-up period (see Table 4). Solid line represents the regression estimate of LV mass across time. None Trace Mild Moderate Severe

4 Ann Thorac Surg ASCH ET AL 2012;94: MITROFLOW AORTIC BOVINE BIOPROSTHESIS 1201 Table 4. Adverse Clinical Events % Freedom a (95% CI) Adverse Event Late Events Hazard Rate (95% CI) 1 Year 5 Years Structural valve dysfunction ( ) ( ) Anticoagulant-related bleeding b ( ) 97.4 ( ) 94.0 ( ) Major embolism ( ) 97.8 ( ) 96.2 ( ) Valve thrombosis ( ) ( ) Endocarditis ( ) 96.6 ( ) 95.2 ( ) Perivalvular leak ( ) 97.3 ( ) 95.1 ( ) Valve reoperation c ( ) 98.8 ( ) 96.7 ( ) Valve explantation ( ) 99.2 ( ) 97.1 ( ) Cardiac-related mortality ( ) 93.7 ( ) 90.1 ( ) Valve-related mortality ( ) 96.9 ( ) 95.3 ( ) All mortality ( ) 89.8 ( ) 77.1 ( ) a Kaplan-Meier freedom from first occurrence of each event. b Major bleeding attributed to warfarin therapy. c Includes valve explantation (n 9) and valve reoperation to repair perivalvular leak (n 1). Linearized hazard rates and Kaplan-Meier freedom from event. Linearized rates (%/patient/year) based on events and follow-up 30 days after operation. Kaplan-Meier freedom from first occurrence of each event at 1 and 5 years after implantation of the Mitroflow valve (n 276; 1,079 patient-years; mean 47.6 months; maximum 65 months). CI confidence interval. up. Although there was a shift from class I to II during the follow-up period, 99%, 97%, and 94% of patients were in NYHA class I or II at 1, 3, and 5 years respectively, compared with 45% at baseline. Comment This prospective multicenter follow-up trial demonstrates excellent safety and durability of the Mitroflow bioprosthetic valve implanted in the aortic position in a North American patient cohort for up to 5 years followup. In this elderly population with significant comorbidities, at 5 years the overall survival was high (77.1%) as was the freedom from valve explantation (97.1%). Valvular degeneration with dysfunction was observed in only 6 patients, and 2 patients required valve replacement for endocarditis. Significant aortic regurgitation was rare ( 2% at any time point), consistent with previous reports [1, 2]. The favorable hemodynamic profile of this valve in this midterm prospective trial is consistent with previous short-term reports on the Mitroflow valve. The good short-term hemodynamic profile previously described by Conte and coworkers [11] and Jamieson and colleagues [10] persists up to 5 years, as reflected by minimal change in the mean gradients and EOA. Moreover, the sustained favorable hemodynamic profile is observed across all valve sizes similar to a previous report using stress echocardiography to assess orifice area [9]. Some of the changes in mean gradients and EOA were statistically significant, but these small differences after 5 years are of questionable clinical relevance. Nonetheless, they do warrant further evaluation for a longer follow-up period. The overall rates of valve deterioration and reoperation are low, consistent with the previous reports by Yankah and associates [2] (1.4% per valve per year) at an average follow-up of 49 months and the ISTHMUS investigators ( patients per year) during a median follow-up of 62 months [8]. Our data emphasize the midterm safety and excellent hemodynamics of aortic valve replacement with the Mitroflow valve in North American patients previously described in single-center European series by Yankah and colleagues[2] and Benhameid and coworkers [3]. How Results Compare With Those of Other Pericardial Bioprostheses Bioprosthetic valves traditionally were limited to elderly populations, in whom durability was of less concern than it is today. Since bioprosthetic valves offer better hemodynamics and do not require anticoagulation, their use in younger patients has become more desirable. However with younger patients receiving these valves, long-term durability has become an important consideration. It is impractical to wait until very long-term durability in humans (out to 20 years) has been established before approval and widespread use of bioprostheses. Therefore it is important that follow-up data be reported as it becomes available. This study provides midterm data (up to 5 years of follow-up) of a valve that has been newly approved by the US Food and Drug Administration. Importantly, our prospective data is supportive of long-term (10 15 year) retrospective data from Europe. In terms of bioprostheses, bovine pericardial valves seem to be less obstructive than porcine valves, as reported by Chambers and colleagues [25]. They randomized patients to receive the Carpentier-Edwards Perimount pericardial valve (Edwards Lifesciences, Irvine, CA) versus the Medtronic Mosaic porcine valve (Medtronic Inc, Minneapolis, MN). Other pericardial stented aortic bioprostheses have also shown excellent

5 1202 ASCH ET AL Ann Thorac Surg MITROFLOW AORTIC BOVINE BIOPROSTHESIS 2012;94: durability and safety in the long term. Banbury and associates [26] reported hemodynamic results at 17 years follow-up (mean 12 years) in a small cohort of patients receiving the bovine Carpentier-Edwards Perimount valve [26]. Interestingly they described a slight decrease in the EOA and an increase in gradients during the initial 10 years after valve implantation, which stabilized thereafter. A similar decline in the valvular performance is seen in our study, although the changes in performance are not considered clinically significant. Further follow-up will be needed to investigate the Mitroflow hemodynamics for a longer follow-up period. As expected, the actuarial freedom from reoperation in our elderly population is very high even after 5 years after valve implantation. This is not surprising, as our results are similar to those of other stented bioprosthetic valves [27]. Limitations Although this study provides additional and complementary data on the long-term performance and safety of the Sorin Mitroflow bovine pericardial aortic valve prosthesis, it still has some limitations. The cohort included in this study is a subset of the initial larger trial [11], so theoretically there could have been a selection bias. However the sites included in this longer follow-up were selected based on their high enrollment, excellent protocol compliance, and ability to amend their consent forms to allow for a longer follow-up. The patients clinical or hemodynamic state was not used to select the sites. This strategy of selecting sites based on protocol adherence allowed the acquisition of high-quality data in the vast majority of patients in this report. Of note, the 6 sites participating in this phase of the study included all their patients to avoid patient selection bias at each center. Indeed when comparing baseline characteristics, our cohort was similar to the patients previously reported in all 28 clinical sites. In addition, although this is the longest follow-up reported for patients included in a North American prospective multicenter trial of the Mitroflow aortic bioprosthesis, it does only represent 5 years. Whether these results will be maintained over a longer period will be addressed only by further follow-up of this cohort. Lastly, since few patients received the smallest valve size (19 mm) in this study, it is uncertain whether the overall results of our study could be applied to the specific and challenging group of patients with the smallest aortic valve annulus. In conclusion, the current report confirms the excellent hemodynamics and survival, with a low rate of complications of the Mitroflow aortic bioprosthesis in a North American population followed for 5 years. The authors wish to thank William B. Dolman and Harvey Kushner, PhD for assistance in the statistical analysis of the data and the preparation of the figures and Harvey Kushner, PhD and Susan Perras, MSN for providing medical writing and editorial assistance. Sorin Group USA, Inc provided funding to support this study and the preparation of this article. References 1. Yankah CA, Schubel J, Buz S, Siniawski H, Hetzer R. Seventeen-year clinical results of 1,037 Mitroflow pericardial heart valve prostheses in the aortic position. J Heart Valve Dis 2005;14: Yankah CA, Pasic M, Musci M, et al. Aortic valve replacement with the Mitroflow pericardial bioprosthesis: durability results up to 21 years. J Thorac Cardiovasc Surg 2008;136: Benhameid O, Jamieson WR, Castella M, et al. Carbomedics Mitroflow pericardial aortic bioprothesis performance in patients aged 60 years and older after 15 years. Thorac Cardiovasc Surg 2008;56: Sjögren J, Gudbjartsson T, Thulin L. Long-term outcome of the Mitroflow pericardial bioprosthesis in the elderly after aortic valve replacement. J Heart Valve Dis 2006;15: Thulin LI, Thilen UJ, Kymle KA. Mitroflow pericardial bioprosthesis in the aortic position. Low incidence of structural valve deterioration in elderly patients during an 11-year follow-up. Scand Cardiovasc J 2000;34: Jamieson WR, Koerfer R, Yankah CA, et al. Mitroflow aortic pericardial bioprosthesis clinical performance. Eur J Cardiothorac Surg 2009;36: García-Bengochea J, Sierra J, González-Juanatey JR, Rubio J, Vega M, Fernández AL, Sánchez D. Left ventricular mass regression after aortic valve replacement with the new Mitroflow 12A pericardial bioprosthesis. J Heart Valve Dis 2006;15: ISTHMUS Investigators. The Italian study on the Mitroflow postoperative results (ISTHMUS): a 20-year, multicenter evaluation of Mitroflow pericardial bioprosthesis. Eur J Cardiothoracic Surg 2011;39: Bleiziffer S, Eichinger WB, Hettich IM, et al. Hemodynamic characterization of the Sorin Mitroflow pericardial bioprosthesis at rest and exercise. J Heart Valve Dis 2009;18: Jamieson WR, Forgie WR, Hayden RI, et al. Hemodynamic performance of Mitroflow aortic pericardial bioprosthesis optimizing management for the small aortic annulus. Thorac Cardiovasc Surg 2010;58: Conte J, Weissman N, Dearani JA, et al. A North American, prospective, multi-center assessment of the Mitroflow aortic pericardial prosthesis. Ann Thorac Surg 2010;90: Poirer NC, Pelletier LC, Pellerin M, Carrier M. 15-year experience with the Carpentier-Edwards pericardial bioprosthesis. Ann Thorac Surg 1998;66 (Suppl):S Aupart MR, Sirinelli AL, Diemont FF, Meurisse YA, Dreyfus XB, Marchand MA. The last generation of pericardial valves in the aortic position: ten-year follow-up in 589 patients. Ann Thorac Surg. 1996;61: Dellgren G, David TE, Raanani E, Armstrong S, Ivanov J, Rakowski H. Late hemodynamic and clinical outcomes of aortic valve replacement with the Carpentier-Edwards Perimount pericardial bioprosthesis. J Thor Cardiovasc Surg 2002;124: McDonald ML, Daly RC, Schaff HV, et al. Hemodynamic performance of small aortic valve bioprostheses: is there a difference? Ann Thorac Surg 1997;63: Rajani R, Mukherjee D, Chambers JB. Doppler echocardiography in normally functioning replacement aortic valves: a review of 129 studies. J Heart Valve Dis 2007;16: Gottdiener JS, Bednarz J, Devereux R, et al. American Society of Echocardiography recommendations for use of echocardiography in clinical trials: a report from the American Society of Echocardiography s Guidelines and Standards Committee and the Task force on Echocardiography in Clinical Trials. J Am Soc Echocardiogr 2004;17: Schiller N, Shah P, Crawford MJ, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two- Dimensional Echocardiograms. J Am Soc Echocardiogr 1989; 2:

6 Ann Thorac Surg ASCH ET AL 2012;94: MITROFLOW AORTIC BOVINE BIOPROSTHESIS Zoghbi WA, Chambers JB, Dumesnil JG, et al. Recommendations for evaluation of prosthetic valves with echocardiography and doppler ultrasound. J Am Soc Echocardiogr 2009;22: Bonow RO, Carabello B, Chatterjee K, et al. ACC/AHA 2006 Practice Guidelines for the Management of Patients With Valvular Heart Disease: Executive Summary. J Am Coll Cardiol 2006;48: Douglas P, DeCara J, Devereux R, et al. Echocardiographic imaging in clinical trials: American Society of Echocardiography Standards for Echocardiography Core Laboratories. J Am Soc Echocardiogr 2009;22: Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16: Lang RM, Bierig M, Devereux RB, et al; Chamber Quantification Writing Group. Recommendations for chamber quantification: a report from the American Society of Echocardiography s Guidelines and Standards Committee and the Chamber Quantification. J Am Soc Echocardiogr 2005;18: Edmunds LH Jr, Clark RE, Cohn LH, Grunkemeier GL, Miller DC, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ann Thorac Surg 1996;62: Chambers JB, Rajani R, Parkin D, et al. Bovine pericardial versus porcine stented replacement aortic valves: early results of a randomized comparison of the Perimount and the Mosaic valves. J Thorac Cardiovasc Surg 2008;136: Banbury MK, Cosgrove DM 3rd, Thomas JD, et al. Hemodynamic stability during 17 years of the Carpentier-Edwards aortic pericardial bioprosthesis. Ann Thorac Surg 2002;73: Mykén PS, Bech-Hansen O. A 20-year experience of 1712 patients with the Biocor porcine bioprosthesis. J Thorac Cardiovasc Surg 2009;137: Member and Individual Subscriber Access to the Online Annals The address of the electronic edition of The Annals is If you are an STS or STSA member or a non-member personal subscriber to the print issue of The Annals, you automatically have a subscription to the online Annals, which entitles you to access the full-text of all articles. To gain full-text access, you will need your CTSNet user name and password. Society members and non-members alike who do not know their CTSNet user name and password should follow the link Forgot your user name or password? that appears below the boxes where you are asked to enter this information when you try to gain full-text access. Your user name and password will be ed to the address you designate. In lieu of the above procedure, if you have forgotten your CTSNet username and/or password, you can always send an to CTSNet via the feedback button from the left navigation menu on the homepage of the online Annals or go directly to We hope that you will view the online Annals and take advantage of the many features available to our subscribers as part of the CTSNet Journals Online. These include inter-journal linking from within the reference sections of Annals articles to over 350 journals available through the HighWire Press collection (HighWire provides the platform for the delivery of the online Annals). There is also crossjournal advanced searching, etoc Alerts, Subject Alerts, Cite-Track, and much more. A listing of these features can be found at We encourage you to visit the online Annals at ats.ctsnetjournals.org and explore by The Society of Thoracic Surgeons Ann Thorac Surg 2012;94: /$36.00 Published by Elsevier Inc