Long-Term Outcome of the Carpentier-Edwards Pericardial Valve in the Aortic Position in Japanese Patients

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1 882 MINAKATA K et al. Circulation Journal ORIGINAL ARTICLE Official Journal of the Japanese Circulation Society Cardiovascular Surgery Long-Term Outcome of the Carpentier-Edwards Pericardial Valve in the Aortic Position in Japanese Patients Kenji Minakata, MD, PhD; Shiro Tanaka, PhD; Yohei Okawa, MD, PhD; Mitsuomi Shimamoto, MD, PhD; Tatsuo Kaneko, MD, PhD; Yoshiharu Takahara, MD, PhD; Hitoshi Yaku, MD, PhD; Kazuo Yamanaka, MD, PhD; Akihiko Usui, MD, PhD; Nobushige Tamura, MD, PhD; Ryuzo Sakata, MD, PhD Background: According to the Japanese Circulation Society guidelines, a bioprosthesis is recommended for aortic valve replacement (AVR) in patients aged 65 years who have no risk factors for thromboembolism. There are few data, however, regarding the actual durability of bioprosthetic valves in Japanese patients. The purpose of this study was to assess the long-term durability of Carpentier-Edwards pericardial (CEP) valves in Japanese AVR patients, and to assess the risk factors for reoperation due to structural valve deterioration (SVD). Methods and Results: From 1986 to 2001, a total of 591 patients underwent AVR with CEP valves in 9 hospitals. Of these, 574 patients (mean age, 71.9±8.5 years) were analyzed in this study. There were 26 in-hospital deaths (4.5%). The 10-year follow-up rate was 82.6% and the median follow-up time was 9.2 years. Freedom from reoperation due to SVD was 99.5%, 96.7%, and 87.5% at 5, 10, and 15 years, respectively. Factors that raised the risk of reoperation due to SVD included younger age at operation and history of prior operation. In patients aged 65 years, freedom from reoperation due to SVD was 94.4% at 15 years. Conclusions: The durability of CEP valves in patients with AVR was excellent, especially in elderly patients. Thus, it seems appropriate to follow the current Japanese Circulation Society recommendations for the use of bioprosthetic valves. (Circ J 2014; 78: ) Key Words: Aortic valve replacement; Bioprosthesis; Durability; Structural valve deterioration According to the recent American College of Cardiology (ACC)/American Heart Association (AHA) treatment guidelines for valvular heart disease published in 2006, 1 a bioprosthetic valve is recommended for aortic valve replacement (AVR) in patients aged 65 years who have no risk factors for thromboembolism. This recommendation is a class IIa recommendation. This is based on the fact that there have been many reports on the excellent durability of tissue valves published over the last 2 decades. 2 7 Since these guidelines were published, a significant trend towards bioprosthetic valves has been emerging even in younger patients, not only in Western countries, but also in Japan. In fact, the annual number of tissue AVR implantations has continued to increase since the late 1990 s, and exceeded the number of mechanical AVR implantations in 2005 according to the annual report issued by the Japanese Association for Thoracic Surgery. 8 This trend continues to gain momentum to the present day. 9 Accordingly, in 2012, the Japanese Circulation Society revised their guidelines for surgical and interventional treatment of valvular heart disease. 10 Their recommendations concerning the use of bioprosthetic valves in patients undergoing AVR includes all patients aged 65 years who have no significant risk factors for thromboembolism. This recommendation is now a class I recommendation, but there have been no studies on the durability of tissue valves in Japanese patients. Certain physicians have raised questions about whether bioprosthetic valves perform equally Received August 21, 2013; revised manuscript received December 24, 2013; accepted January 7, 2014; released online March 11, 2014 Time for primary review: 56 days Kyoto University Graduate School of Medicine, Kyoto (K.M., R.S.); Kyoto University Graduate School of Public Health, Kyoto (S.T.); Cardiovascular Center Hokkaido Ohno Hospital, Sapporo (Y.O.); Shizuoka City Shizuoka Hospital, Shizuoka (M.S.); Gunma Cardiovascular Center, Maebashi (T.K.); Funabashi Municipal Medical Center, Funabashi (Y.T.); University Hospital, Kyoto Prefectural University of Medicine, Kyoto (H.Y.); Tenri Hospital, Tenri (K.Y.); Nagoya University Hospital, Nagoya (A.U.); and Kumamoto Central Hospital, Kumamoto (N.T.), Japan Mailing address: Kenji Minakata, MD, PhD, Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto , Japan. minakata@kuhp.kyoto-u.ac.jp ISSN doi: /circj.CJ All rights are reserved to the Japanese Circulation Society. For permissions, please cj@j-circ.or.jp

2 Durability of the Pericardial Valve in Japan 883 Figure 1. Flow chart of patient selection and follow-up. AVR, aortic valve replacement; CEP, Carpentier-Edwards pericardial valve. well and last as long in Japanese patients as they do in other patient populations. Thus, we organized a multicenter research group, which we called the CEPIA-J Study Group (Durability Evaluation of Carpentier-Edwards PERIMOUNT Pericardial Valve in Aortic Position in Japanese Patients Study Group). The aims of this study were as follows: (1) to assess the long-term durability of pericardial valves in Japanese patients undergoing AVR; and (2) to identify the factors that influence outcomes, including all-cause death and valve-related adverse events including thromboembolic events, major bleeding, and prosthetic valve endocarditis (PVE), as well as reoperation due to structural valve deterioration (SVD). Methods Patients In Japan, the Carpentier-Edwards PERIMOUNT pericardial (CEP) bioprosthesis (Edwards Lifesciences, Irvine, CA, USA) was approved for clinical use in All adult patients undergoing AVR using CEP valves in the participating 9 hospitals (Supplementary File 1; Appendix S1) from January 1986 to December 2001 were included in this study. Of note, those who underwent aortic root replacement with composite grafts, concomitant procedures such as coronary artery bypass grafting, mitral or tricuspid valve repair or replacement, and aortic aneurysm repair were also included. A flowchart of the patient selection and follow-up process is shown in Figure 1. At first, 591 patients were identified as eligible for this study. Of these, 574 patients were enrolled as study patients. This cohort represented approximately 11% of all the patients undergoing AVR with CEP valves in all of Japan during the study period. Patient characteristics and operative data were obtained from medical records at each study facility by independent clinical research coordinators (Supplementary File 1; Appendix S2) according to pre-specified criteria. In addition, all of the patients who survived the surgery underwent follow-up surveys. Late outcome was determined from medical records when available, from written correspondence with patients physicians, or direct patient contact via mailed questionnaires or telephone interviews when necessary. Clinical data at the latest follow-up were collected by contacting referring physicians. This study was approved by the Institutional Review Board at all the participating hospitals and the Ethics Committee of the Kyoto University Graduate School and Faculty of Medicine. All patients or their family members gave informed consent. Table 1. Baseline Characteristics Characteristics n % No. patients 574 Mean age (years) 71.9±8.5 Age range (years) Female gender Age 65 years BSA (m 2 ) 1.50±0.17 Comorbidity Hypertension 54.9 Dyslipidemia 13.4 Diabetes mellitus (on insulin) 11.2 (2.2) Atrial fibrillation 21.2 COPD 1.3 Peripheral artery disease 7.8 Chronic kidney disease 44.9 Hemodialysis 0.9 Malignancy 10.4 Coronary artery disease 26.9 Old myocardial infarction 7.1 LVEF <40% 8.9 Prior stroke 9.3 Prior intracranial hemorrhage 1.3 NYHA functional class I/II 60.3 III/IV 39.7 Aortic valve pathology Bicuspid 15.0 Tricuspid 82.8 Rheumatic 4.3 Infective endocarditis (active) 2.2 Infective endocarditis (healed) 0.4 Prosthetic valve dysfunction 2.1 Aortic valve lesion Aortic stenosis 35.8 Aortic regurgitation 35.1 Mixed lesion 29.2 BSA, body surface area; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association. Definitions of Events Definitions of SVD, and other valve-related events are based on

3 884 MINAKATA K et al. Table 2. Operative Variables Variables n % No. patients 574 Valve size (mm) Redo sternotomy Concomitant procedure Coronary artery bypass grafting Aortic annular enlargement Mitral valve repair Mitral valve replacement Tricuspid valve repair Aortic aneurysm repair (root/composite) Aortic aneurysm repair (ascending aorta) Aortic aneurysm repair (aortic arch) Mean aortic cross-clamp time (min) 100±41 Mean cardiopulmonary bypass time (min) 139±59 the Society of Thoracic Surgeons (STS) guidelines for reporting mortality and morbidity after cardiac valve interventions, published in In short, the term structural valve deterioration refers to changes intrinsic to the valve, such as wear, fracture, poppet escape, calcification, leaflet tear, stent creep, and suture line disruption of components of a prosthetic valve. Nonstructural dysfunction refers to any abnormality not intrinsic to the valve itself that resulted in stenosis or regurgitation of the operated valve or hemolysis. The term non-structural dysfunction refers to problems (exclusive of thrombosis and infection) that do not directly involve valve components yet result in dysfunction of an operated valve, as diagnosed by reoperation, autopsy, or clinical investigation. Non-structural dysfunction includes entrapment by pannus, tissue, or suture; paravalvular leakage; inappropriate sizing or positioning; residual leakage or obstruction after valve implantation or repair; and clinically important intravascular hemolytic anemia. Thromboembolism refers to any embolic event that occurs in the absence of infection after the immediate perioperative period. A thromboembolism may be manifested by a neurologic event or a non-cerebral embolic event. A neurologic event includes any central, new neurologic deficit, whether temporary or permanent, whether focal or global, that occurs after the patient emerges from anesthesia. Central neurologic events that were clearly related to aortic, internal carotid artery, or vertebral artery disease, such as acute thrombotic occlusion, atheroembolism, or spontaneous arterial dissection, were not counted. When there was no detailed information about the event, however, any neurological event was counted as a thromboembolism in this study. A bleeding event was defined as any episode of major internal or external bleeding that caused death, hospitalization, or permanent injury or necessitated transfusion, regardless of anticoagulation status. Valve-related death was defined as any death caused by SVD, non-structural dysfunction, valve thrombosis, embolism, bleeding event, or operated valve endocarditis; death related to reintervention on the operated valve; or sudden, unexplained death. Deaths caused by heart failure in patients with advanced myocardial disease and satisfactorily functioning cardiac valves Table 3. Postoperative and Follow-up Data Variables n % No. patients day mortality In-hospital mortality Isolated AVR 1.9 Complex AVR 7.2 First-time AVR 3.8 Redo AVR 10 Causes of in-hospital death (n=26) Cardiovascular Respiratory Gastrointestinal Infection Renal Hemorrhage Multi-organ Others Late death Cause of late death Malignancy Cardiac Valve-related Respiratory Cerebrovascular Hemorrhage Renal Infection Gastro-intestinal Liver Late complications Prosthetic valve endocarditis Thromboembolism months 1 >3 months 37 Major bleeding months 2 >3 months 46 Gastrointestinal Intracranial All reoperation Indication of reoperation Structural valve deterioration 18 Prosthetic valve endocarditis 4 Paravalvular leak 1 Other 1 AVR, aortic valve replacement. were not counted. In-hospital mortality was defined as death occurring within 30 days of surgery or at any time during the index hospitalization. Statistical Analysis All clinical events were evaluated at the participating hospitals, and then assessed by the independent clinical events evaluation committee (Supplementary File 1; Appendix S3) if necessary. Postoperative overall survival, freedom from valve-related death, valve-related events, and reoperation due to SVD were estimated

4 Durability of the Pericardial Valve in Japan 885 Figure 2. Freedom from (Left) all-cause death and (Right) valve-related death. AVR, aortic valve replacement. using the Kaplan-Meier method. The association of potential risk factors to survival and events was assessed with log-rank test. All continuous variables are expressed as mean ± SD. All P-values are 2-sided and P<0.05 was considered statistically significant. All data analysis was carried out by an academic statistician (S.T.) using SAS version 9.2 (SAS Institute, Cary, NC, USA). Results Patient baseline characteristics are given in Table 1. The total number of patients was 574, with a mean age of 71.9±8.5 years (range, years). A total of 90.8% of patients were aged 65 years. Their mean body surface area was 1.50±0.17 m 2. In terms of preoperative comorbidities, 54.9% had systemic hypertension, 13.4% had dyslipidemia, and 11.2% had diabetes mellitus. Also, 21.2% of patients had atrial fibrillation (AF). Chronic kidney disease (defined as estimated glomerular filtration rate [egfr] <60ml min m 2, calculated using the Modification of Diet in Renal Disease Formula for Japanese Patients: egfr [ml min m 2 ]=194 serum creatin ine age [if female] 12 ) was very common and found in 44.9% of patients. Coronary artery disease was also common, identified in 26.9% of patients. Left ventricular ejection fraction (LVEF)<40% was found in only 8.9% of patients. In terms of valve pathology, congenital bicuspid valve disease was identified in 15.0% of patients, whereas 82.8% of patients were found to have tricuspid aortic valve. Rheumatic pathology was rare, found in only 4.3% of patients. Infective endocarditis and previously implanted prosthetic valve dysfunction were also rare, found in only 2.6% and 2.1% of patients, respectively. Aortic valve lesion as the reason for AVR consisted of stenosis in 35.8%, regurgitation in 35.1%, and mixed lesions in 29.2%. With regard to operative variables, size of pericardial valve used is given in Table 2. The most commonly used size was 21 mm, followed by 23 mm, then 19 mm. A few patients (3.7%) had a prior history of open heart surgery, predominantly on aortic valves. Isolated AVR was performed in 57.0% of patients, while combined procedures were performed in 43.0%. Details of combined procedures are given in Table 2. The mean aortic cross-clamp time and cardiopulmonary bypass time were 100±41 min and 139±596 min, respectively. Early Outcome There were 26 in-hospital deaths (4.5% of the total cohort). Inhospital mortalities in isolated AVR and complex AVR (concomitant with other procedures) were 1.9% and 7.2%, respectively. Also, redo patients had a higher mortality rate compared to that of first-time AVR patients (10% vs. 3.8%). The causes of in-hospital death are listed in Table 3. Late Outcome The mean follow-up period was 8.2±5.4 years (maximum follow-up, 27 years; median follow-up, 9.2 years). The 10-year follow-up rate was 82.6%. There were 269 late deaths. The causes of late death are given in Table 3. The leading cause of late death was malignant neoplasm, followed by cardiac- and valve-related deaths. In terms of late complications, there were only 8 cases of PVE (1.6%). Thromboembolic events and major bleeding occurred in 7.5% and 9.5% of patients, respectively. The majority of the thromboembolic events were strokes. The most common major bleeding incidents were gastrointestinal bleeding, followed by intracranial bleeding. The number of thromboembolism and major bleeding events according to the

5 886 MINAKATA K et al. Figure 3. Freedom from (Left) thromboembolic events and (Right) bleeding events. AVR, aortic valve replacement. timing (within 3 months or after 3 months of operation) are listed in Table 3. During the follow-up period, there were 24 reoperations. The indications for reoperation were SVD in 18, PVE in 4, and paravalvular leak in 1. One patient underwent reoperation due to progressive mitral valve disease, when a previously implanted CEP valve in the aortic position was also explanted. Among 18 patients who required reoperation due to SVD, the mean age at initial operation was 49.5 years (range, years) and female gender was predominant (67%). The valve pathology indication for reoperation included stenosis in 39%, regurgitation in 28%, and mixed lesions in 33%. The mean duration from initial operation to reoperation was 11.4 years (range, years). At reoperation, 50% of the patients received a bioprosthetic valve again. There were 3 in-hospital deaths among these patients (mortality, 12.5%). Survival curves estimated using the Kaplan-Meier method are shown in Figure 2. Freedom from all-cause death was 78.9%, 56.8%, and 36.2% at 5, 10, and 15 years, respectively. Also, freedom from valve-related death was 98.1%, 93.1%, and 90.8% at 5, 10, and 15 years, respectively. Risk factors for allcause death analyzed using log-rank test included older age (P<0.01), depressed LVEF (defined as <40%, P<0.05), complex AVR (combined with other procedures, P<0.01), redo (P<0.01), coronary artery disease (P<0.01), diabetes mellitus (P<0.01), chronic kidney disease (P<0.01), and advanced New York Heart Association functional class (P<0.01). Freedom from valve-related events is shown in Figures 3,4. Freedom from thromboembolic events at 15 years was 87.5%. The rate of thromboembolic events was 0.83%/patient-year. Also, freedom from bleeding events at 15 years was 83.2%. The rate of bleeding events was 1.12%/patient-year. Freedom from PVE at 15 years was 97.5%. Preoperative AF was found to be a significant risk factor for thromboembolism on log-rank test (P<0.01). Freedom from reoperation due to SVD, as shown in Figure 4, was 99.3%, 96.7%, and 87.5% at 5, 10, and 15 years, respectively. In patients aged 65 years at the time of operation, freedom from reoperation due to SVD was 99.3%, 97.4%, and 94.4% at 5, 10, and 15 years, respectively. Younger age at the time of operation was identified as a significant risk factor for reoperation due to SVD (log-rank P<0.01). Also, prior history of aortic valve operation was a significant risk factor for reoperation due to SVD (log-rank P<0.01). Freedom from each event at 5, 10, and 15 years and the 95% confidence intervals are listed in Table S1. Discussion This study is, to the best of our knowledge, the largest retrospective study on the long-term outcomes for Japanese patients undergoing AVR with tissue valves. At present, there are 6 types of stented tissue valves currently available in Japan. Among these bioprostheses, the CEP valve is the oldest. In fact, it was approved in 1985 in Japan, and has been widely used ever since. Another unique point of this study is that this cohort represented approximately 11% of all AVR using CEP valves performed in all of Japan during the study period, which should certainly strengthen the clinical significance of this study. The present results are compared to those of other studies in Table 4. Freedom from reoperation due to SVD at 15 years was 87.5% overall, and 94.4% in patients aged 65 years in the present study. The durability of pericardial valves was found to be similar to the results reported by other teams in the USA,

6 Durability of the Pericardial Valve in Japan 887 Figure 4. Freedom from reoperation due to structural valve deterioration (SVD) (Left) in all patients and (Right) stratified by age at operation. AVR, aortic valve replacement. Table 4. Comparisons of Clinical Data First author Mean follow-up Thromboembolism Bleeding Journal/Year Freedom from reoperation due to SVD n (Location) (years) (%/patient-year) (%/patient-year) Present study (Japan) Circ J % at 15 years (mean age, 71.9 years) 94.4% at 15 years, age 65 years McClure (Boston, USA) Banbury (Cleveland, USA) Poirer (Quebec, Canada) Pellerin (Paris, France) Aupart (Tours, France) Ann Thorac Surg % at 15 years, age years 99.5% at 15 years, age >75 years 1, Ann Thorac 80% at 15 years, age years N/A N/A Surg Ann Thorac Surg % at 15 years, age 70 years 310 Ann Thorac Surg % at 14 years, age years 100% at 14 years, age 70 years Ann Thorac 83% at 13 years (mean age, 65 years) Surg J Heart Valve Dis SVD, structural valve deterioration. 77% at 18 years, age years 99% at 18 years, age >70 years 1, Canada, and France (these studies reported freedom from reoperation due to SVD ranging from 83% to 100% at >10 years postoperatively in patients 60 years). Thus, there does not seem to be any difference due to race in terms of the durability of these pericardial valves. As an alternative to pericardial valves, the porcine bioprosthesis is another choice for AVR. The long-term durability of porcine valves has also been reported to be excellent. David et al reported that freedom from reoperation due to SVD at 20 years in patients who had undergone AVR with Hancock II porcine bioprosthetic valves at ages 60 70, and 70 were 85.2% and 99.8%, respectively. 13 There are very few data comparing pericardial valves with porcine valves in terms of durability. Gao et al reported that there were no differences in survival and valve-related complications, including thromboembolism and endocarditis, between the valves, but the 10-year freedom from explant was lower for porcine valves than for pericardial valves. 14 Perhaps, the most important difference between pericardial valves and porcine valves is their hemodynamic performance. Previous studies have shown that pericardial bioprostheses have better echocardiographic hemodynamics in the aortic position compared to porcine valves, 15,16 but pericardial valves do not

7 888 MINAKATA K et al. provide any survival advantage over porcine valves in patients aged 65 years undergoing AVR. 17 Since the first-generation pericardial valve was made available in the early 1970 s, various structural refinements and tissue treatments have been applied to prevent wear and calcification of the leaflets that cause SVD. The CEP bioprosthesis is unique in several ways: (1) the 3 leaflets are uniform in thickness and elasticity as a result of computer-aided design; (2) leaflets are mounted inside an Elgiloy TM (cobalt-nickel alloy) wire stent for flexibility and distendability; and (3) leaflets are treated with the calcium mitigation agents polysorbate-80 and ethanol (XenoLogiX TM ) as an advanced anti-calcification treatment. 6 Recently, a third-generation anti-calcification treatment, called Thermafix TM, was added to the newer model of the CEP, called the CEP-Magna, which has a true supra-annular configuration to achieve better hemodynamics and flow characteristics, especially in small valves. 15 Thermafix technology has been shown to yield better prevention of late calcification of the leaflet in vivo. Thus, it is expected to have better long-term durability than CEP valves, although this needs to be verified by further clinical study. Despite the aforementioned diligent efforts to develop anticalcification technology, SVD is inevitable for all AVR recipients over time. It was obvious that in the present study, as in other studies, many patients may have developed SVD to some extent, but they died from other causes before reoperation became necessary. Thus, most younger patients will probably require reoperation eventually due to SVD at some point. Historically, reoperation has carried a higher risk of perioperative mortality and morbidities including bleeding, myocardial dysfunction, surgical site infection, kidney dysfunction, and cerebrovascular incidents. The contemporary overall risk of reoperation, however, has definitely decreased due to improvements and refinements in surgical techniques and perioperative management. Potter et al reported that the risk of reoperation for AVR is similar to that for primary AVR after excluding patients with PVE, and the data support the extended use of bioprosthetic valves in younger patients. 18 With regard to anticoagulation therapy, it is recommended to use warfarin for 3 months after surgery unless contraindicated according to the published treatment guidelines. 1 Early anticoagulation is thought to decrease the risk of thromboembolism while the cloth sewing ring is endothelialized. It is a common protocol that warfarin is discontinued after 3 months in patients without risk factors for thromboembolism such as chronic AF in most of the hospitals in this study. The rate of thromboembolism was 0.83%/patient-year in the current study, and this risk increases in patients with chronic AF (log-rank P<0.01). It should be noted that in this study, a significant number of events defined as thromboembolic events may have been misdiagnosed due to a lack of detailed information, which is common in retrospective cohort studies. Conditions that can be mistaken for thromboembolic events include atheromatous plaque of the carotid or vertebral arteries, or other intracranial artery diseases, which are common causes of cerebrovascular events that do not fit the definition of thromboembolism. Although the occurrence of thromboembolic events may have been overestimated, the present findings are similar to those of other studies (Table 4). In contrast, the rate of bleeding was 1.12%/patient-year in the present study, which was slightly higher than in other studies (Table 4). These risks may be balanced by more meticulous control of anticoagulation, but we do not have sufficient data regarding anticoagulation therapy at the time of thromboembolic events or major bleeding events during the follow-up period, making it difficult to discuss this in greater detail. Study Limitations There were several limitations in this study. First, this was a retrospective, non-randomized study. Also, many of the patients died several years prior to the study, and the events occurred years before the study, making it difficult to obtain accurate information, especially for valve-related events. Likewise, the 10-year follow-up completeness was 82.6%. These factors may have influenced the results significantly. Conclusions The durability of the CEP bioprosthesis in the aortic position is excellent in the Japanese population, with a very low risk of reoperation due to SVD, particularly in elderly patients aged 65 years. Thus, it is appropriate to follow the current indications concerning bioprosthetic valves issued by the Japanese Circulation Society and contained in the ACC/AHA guidelines. Acknowledgments We are indebted to the participating hospitals, investigators, and clinical research coordinators for their great contributions to data collection. The hospitals, clinical research coordinators and investigators are listed in Appendices S1 and S2. Also, we deeply thank the Independent Clinical Events Evaluation Committee of this study listed in Appendix S3. This work was supported by an educational grant from the Research Institute for Production Development (Kyoto, Japan). References 1. American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; Bonow RO, Carabello BA, Kanu C, de Leon AC Jr, Faxon DP, Freed MD, et al. 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 (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): Developed in collaboration with the Society of Cardiovascular Anesthesiologists: Endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation 2006; 114: e84 e231, doi: / CIRCULATIONAHA McClure RS, Narayanasamy N, Wiegerinck E, Lipsitz S, Maloney A, Byrne JG, et al. Late outcomes for aortic valve replacement with the Carpentier-Edwards pericardial bioprosthesis: Up to 17-year followup in 1,000 patients. Ann Thorac Surg 2010; 89: Banbury MK, Cosgrove DM 3rd, White JA, Blackstone EH, Frater RW, Okies JE. Age and valve size effect on the long-term durability of the Carpentier-Edwards aortic pericardial bioprosthesis. 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8 Durability of the Pericardial Valve in Japan 889 Cardiovasc Surg 2012; 60: Okita Y, Okada Y, Otsuji Y, Komeda M, Nakatani S, Matsuzaki M, et al. Guidelines for Surgical and Interventional Treatment of Valvular Heart Disease. Japanese Circulation Society, or.jp/guideline/pdf/jcs2012_ookita_h.pdf. (accessed 21 August, 2013). 11. Akins CW, Miller DC, Turina MI, Kouchoukos NT, Blackstone EH, Grunkemeier GL, et al. Guidelines for reporting mortality and morbidity after cardiac valve interventions. Ann Thorac Surg 2008; 85: Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009; 53: David TE, Armstrong S, Maganti M. Hancock II Bioprosthesis for aortic valve replacement: The gold standard of bioprosthetic valves durability? Ann Thorac Surg 2010; 90: Gao G, Wu Y, Grunkemeier GL, Furnary AP, Starr A. Durability of pericardial versus porcine aortic valves. J Am Coll Cardiol 2004; 44: Okamura H, Yamaguchi A, Yoshizaki T, Nagano H, Itoh S, Morita H, et al. Clinical outcomes and hemodynamics of the 19-mm Perimount Magna bioprosthesis in an aortic position: Comparison with the 19-mm Medtronic Mosaic Ultra Valve. Circ J 2012; 76: Eichinger WB, Botzenhardt F, Keithahn A, Guenzinger R, Bleiziffer S, Wagner I, et al. Exercise hemodynamics of bovine versus porcine bioprostheses: A prospective randomized comparison of the mosaic and perimount aortic valves. J Thorac Cardiovasc Surg 2005; 129: Said SM, Ashikhmina E, Greason KL, Suri RM, Park SJ, Daly RC, et al. Do pericardial bioprostheses improve outcome of elderly patients undergoing aortic valve replacement? Ann Thorac Surg 2012; 93: Potter DD, Sundt TM 3rd, Zehr KJ, Dearani JA, Daly RC, Mullany CJ, et al. Operative risk of reoperative aortic valve replacement. J Thorac Cardiovasc Surg 2005; 129: Supplementary Files Supplementary File 1 Appendix S1. Participating hospitals and investigators Appendix S2. Independent clinical research coordinators Appendix S3. Independent clinical events evaluation committee Table S1. Freedom from events (%) Please find supplementary file(s);