The St. Jude Medical mechanical valve is a low-profile,

Twenty-Five Year Experience With the St. Jude Medical Mechanical Valve Prosthesis J. Matthew Toole, MD, Martha R. Stroud, MS, John M. Kratz, MD, Arthur J. Crumbley III, MD, Scott M. Bradley, MD, Fred A. Crawford, Jr, MD, and John S. Ikonomidis, MD, PhD Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina Background. We evaluated all adult St. Jude mechanical valve recipients at our institution since the initial implant in January 1979 and now present our 25-year experience. Methods. Nine hundred forty-five valve recipients were followed prospectively at 12-month intervals from January 1979 to December 2007. Results. Operative mortality was 3% in the aortic valve recipients and 5% in the mitral valve recipients. Follow-up was 95% complete. Among aortic valve recipients, late actuarial survival was 81% 2%, 59% 2%, 41% 3%, 28% 3%, and 17% 4% at 5, 10, 15, 20, and 25 years, respectively. Twenty-five year freedom from reoperation, thromboembolism, bleeding, and endocarditis was 90% 2%, 69% 5%, 67% 3%, and 9% 3 2% respectively. Among mitral valve recipients late actuarial survival was 84% 2%, 63% 3%, 44% 3%, 31% 3%, and 23% 4% at 5, 10, 15, 20, and 25 years, respectively. Twenty-five year freedom from reoperation, thromboembolism, bleeding and endocarditis was 81% 10%, 52% 8%, 64% 6%, and 97% 1%. Freedom from valve-related mortality and morbidity at 25 years was 26% 7% and 29% 6% for aortic and mitral valve replacement, respectively. Freedom from valve-related mortality was 66% 8% and 87% 3% for aortic and mitral valve replacement, respectively. Conclusions. These results compare favorably with those for other mechanical prostheses. After two and a half decades of observation with close follow-up, the St. Jude mechanical valve continues to be a reliable prosthesis. (Ann Thorac Surg 2010;89:1402 9) 2010 by The Society of Thoracic Surgeons The St. Jude Medical mechanical valve is a low-profile, bileaflet valve constructed of pyrolytic carbon. The central flow design was originally believed to offer a lower transvalvular gradient than other mechanical valves, and its construction suggested that it would be durable and thromboresistant. These attributes have been substantiated by early, intermediate, and late reports of the use of this valve [1 11]. All valve replacement patients at the Medical University of South Carolina have been prospectively enrolled in an ongoing database since the original clinical trial of this valve commenced in January 1979 at our institution. During this period, 54% of patients at this institution received tissue valves. This report includes patients older than 18 years of age undergoing isolated aortic valve replacement (AVR) or mitral valve replacement (MVR) with or without coronary artery bypass grafting. This report does not include patients undergoing combined valve procedures. We have previously reported a 4-year [1], 10-year [2], 15-year [7] and 20-year [11] experience in 1984, 1992, 1999, and 2003, respectively. The purpose of this report is to analyze Accepted for publication Jan 20, 2010. Presented at the Fifty-sixth Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 4 7, 2009. Address correspondence to Dr Ikonomidis, Cardiothoracic Surgery, Medical University of South Carolina, Ste 7030, 25 Courtenay Dr, Charleston, SC 29425; e-mail: ikonomij@musc.edu. the results of our 25-year experience with the St. Jude Medical mechanical valve. Patients and Methods Patients Between January 1979 and December 2007, 945 patients underwent AVR (537 patients) or MVR (408 patients). The preoperative and intraoperative characteristics of the AVR and MVR cohorts are given in Table 1. All patients undergoing valve replacement at the Medical University of South Carolina since 1979 were prospectively entered into a computer database and were followed up on an annual basis either at this hospital or by the referring physician. In addition, yearly questionnaires were mailed to all patients. If the questionnaires were not returned or the patient reported an adverse event, telephone or personal interviews were conducted. For deaths, the Social Security Death Index was used to confirm the date. In addition, a copy of the death certificate was obtained to confirm the cause of death. Forty-five patients were lost to follow-up (25 AVR, 20 MVR); therefore, follow-up was 95% complete and ranged from 1 month to 28 years (mean, 9 years). The closing interval for this study was 12 months. This study was approved by the Institutional Review Board of the Medical University of South Carolina, and individual consent was waived. Morbidity and mortality were stringently defined according to the 2010 by The Society of Thoracic Surgeons 0003-4975/10/$36.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2010.01.045

Ann Thorac Surg TOOLE ET AL 2010;89:1402 9 ST. JUDE MECHANICAL VALVE AT 25 YEARS 1403 Table 1. Patient Demographics Variable AVR MVR Total number 537 408 Age (y) Range 18 85 18 83 Mean SD 56 14 53 13 Sex Male 376 (70%) 168 (41%) Female 161 (30%) 140 (59%) Etiology Rheumatic 75 (14%) 166 (41%) Endocarditis 39 (7%) 25 (6%) Calcific 279 (52%) 20 (4%) Reoperative 43 (8%) 64 (15%) Ischemic 0 (0%) 39 (10%) Degenerative 49 (9%) 85 (21%) Congenital 49 (9%) 7 (2%) Other 3 (1%) 3 (1%) Lesion Stenosis 299 (56%) 98 (24%) Insufficiency 170 (32%) 256 (63%) Mixed 68 (13%) 54 (13%) Valve sizes 19 mm 81 (15%) 0 (0%) 21 mm 139 (26%) 1 (0.2%) 23 mm 157 (29%) 3 (1%) 25 mm 95 (18%) 8 (2%) 27 mm 49 (9%) 56 (14%) 29 mm 11 (2%) 149 (36%) 31 mm 4 (1%) 121 (30%) 33 mm 1 (0.2%) 70 (17%) Associated CABG 170 (32%) 80 (20%) Preoperative NYHA class I 26 (5%) 12 (3%) II 99 (18%) 35 (9%) III 269 (50%) 195 (48%) IV 143 (27%) 166 (41%) Operative mortality 17 (3.2%) 20 (4.9%) Patient follow-up (y) 9 6 9 7 Lost to follow-up 25 (5%) 20 (6%) AVR aortic valve replacement; CABG coronary artery bypass grafting; MVR mitral valve replacement; NYHA New York Heart Association. guidelines of The Society of Thoracic Surgeons and the American Association for Thoracic Surgery [12]. Operative techniques were similar to those previously reported [1, 2, 7]. Briefly, standard cardiopulmonary bypass was established using a disposable bubble or membrane oxygenator and moderate hypothermia (26 to 34 C). Cold crystalloid or blood cardioplegia was used for myocardial protection according to surgeon preference. An increased tendency toward the use of retrograde blood cardioplegia was observed in later years. After debriding the valve annulus, the prosthesis was secured using interrupted sutures of 2-0 Dacron (Ethicon, Inc, Raleigh, NC). Sutures were carefully placed from above and through the annulus so that the valve annulus is everted when the sutures are tied, thus inserting the valve in an intra-annular position. Beginning in 1988, the subvalvular apparatus of the mitral valve was preserved whenever possible. Valve sizes for the two groups ranged from 19 mm to 33 mm (Table 1). In the AVR group the standard St. Jude Medical (Minneapolis, MN) mechanical prosthesis was used in 378 patients. The Masters series was used in 100 patients, the Hemodynamic Plus valve was used in 23 patients, and the Regent was used in 36 patients. In the MVR group, the standard St. Jude Medical valve was used in 266 patients and the Masters Series was used in 142 patients. Thirty-three patients received AVR with valve sewing rings impregnated with Silzone as did 37 patients undergoing MVR. Heparin (5,000 units subcutaneously every 6 to 12 hours depending on surgeon preference) was started on the first postoperative day and was continued until the prothrombin time or, more recently, the international normalized ratio (INR) was regulated with the administration of warfarin sodium. Early in our experience, the INR was maintained at 2.5 to 3.5. More recently, we have recommended an INR of 2 for patients who have undergone AVR and 2.0 to 2.5 for MVR. The warfarin dosing was regulated by the surgeon during hospitalization and during early follow-up and thereafter by the referring physician. Statistical Analysis Continuous variables are reported as mean one standard deviation, and the categorical variables are repre- Table 2. Univariate Associations With Operative and Late Death Variable p Value Operative death AVR Decreased EOAI 0.004 NYHA IV 0.022 MVR NYHA IV 0.022 Increased age 0.009 Late death AVR Increased age 0.0005 NYHA III IV 0.0005 Concomitant CABG 0.0005 AA race 0.0376 MVR Increased age 0.0005 Ischemic etiology 0.0005 NYHA IV 0.0233 AA race African American race; AVR aortic valve replacement; CABG coronary artery bypass grafting; EOAI effective orifice area index; MVR mitral valve replacement; NYHA New York Heart Association.

1404 TOOLE ET AL Ann Thorac Surg ST. JUDE MECHANICAL VALVE AT 25 YEARS 2010;89:1402 9 Table 3. Multivariate Associations With Operative and Late Death Variable p Value Odds Ratio 95% Confidence Limit Operative death AVR Decreased EOAI 0.006 0.022 0.001, 0.331 NYHA IV 0.035 2.89 1.08, 7.76 MVR NYHA IV 0.004 4.55 1.61, 12.88 Increased age 0.014 1.05 1.01, 1.10 Late death AVR Increased age 0.0005 1.04 1.03, 1.06 NYHA III IV 0.004 1.65 1.20, 2.28 Concomitant CABG 0.0005 1.77 1.37, 2.29 AA race 0.0005 2.47 1.82, 3.36 MVR Increased age 0.0005 1.03 1.02, 1.05 Ischemic etiology 0.022 1.70 1.11, 2.61 NYHA IV 0.048 1.34 1.003, 1.78 AA race African American race; AVR aortic valve replacement; CABG coronary artery bypass grafting; EOAI effective orifice area index; MVR mitral valve replacement; NYHA New York Heart Association. sented as percentages. Actuarial curves were constructed to describe mortality and the incidence of valve-related complications using the Kaplan-Meier technique and are reported with the standard error of the mean [13 15]. Because actuarial analysis is known to overestimate the incidence of nonfatal end points, cumulative incidence curves were constructed for both the AVR and MVR groups for the end points of reoperation, endocarditis, thromboembolic events, and anticoagulation-related hemorrhage [16]. Linearized rates, used to describe multiple events, were reported as percent per patient year. Independent factors associated with operative and late death were identified using logistic regression [17] and Fig 1. Actuarial survival for aortic valve replacement (AVR) and mitral valve replacement (MVR). Fig 2. Actuarial and cumulative freedom from reoperation for aortic valve replacement (AVR) and mitral valve replacement (MVR). Cox proportional hazards regression model [18], respectively. Variables used for both the AVR and MVR groups are summarized in the Appendix. Effective orifice areas (EOAs) used for analysis were kindly provided by St. Jude Medical. Results Survival In the AVR cohort there were 17 operative and 268 late deaths (54 valve-related, 93 cardiac, 76 noncardiac, and 45 sudden or unknown). In the MVR group there were 20 operative and 192 late deaths (27 valve-related, 78 cardiac, 57 noncardiac, and 30 sudden or unknown). Logistic regression analysis (Table 3) showed that decreased effective orifice area index (EOAI) and New York Heart Association (NYHA) class IV were independent predictors of operative death. Preoperative NYHA class IV and increased age were predictors of death in the MVR cohort (Table 2). Actuarial survivorship (Fig 1) at 25 years was 17% 3% (AVR) and 22% 3% (MVR). Cox analysis showed that independent predictors of late death in the AVR group were African American ethnicity, NYHA class III or IV, concomitant coronary artery bypass graft, and increasing age (Table 3). The EOAI was univariately (p 0.0002) but not multivariately predictive of late death. Among AVR recipients aortic stenosis was univariately (p 0.02) but not multivariately predictive of late mortality. Independent predictors of late death after MVR were NYHA class IV, ischemic etiology, and increased age (Table 2). Endocarditis as an indication for valve replacement did not affect perioperative or longterm survival (Table 3). was performed for 34 patients in the AVR cohort and 20 patients in the MVR cohort. Reasons for reoperation in the AVR cohort were perivalvular dehiscence in 6 patients, endocarditis in 19 patients, and other causes in 9 patients. Reasons for reoperation in the MVR

Ann Thorac Surg TOOLE ET AL 2010;89:1402 9 ST. JUDE MECHANICAL VALVE AT 25 YEARS 1405 cohort were perivalvular dehiscence in 10 patients, prosthetic valve endocarditis (PVE) in 8 patients, and other causes in 2 patients. Structural valve deterioration was not seen in either the AVR or the MVR group. Actuarial and cumulative incidence freedom from reoperation is given in Figure 2. In the AVR group, actuarial freedom from reoperation was 90% 2% at 25 years. Cumulative freedom was 93% 1% at 25 years. In the MVR group actuarial freedom from operation was 81% 10% at 25 years. Cumulative freedom was 92% 3% at 25 years. Thromboembolic Complications In the AVR group thromboembolism occurred in 73 patients (91 total events). Of these, 47 were defined as strokes (13 were fatal), and 29, as transient ischemic attacks. Five patients had peripheral embolic events (1 was fatal), and 10 patients had valve thrombosis (3 were fatal). Thromboembolism occurred in 82 patients in the MVR group (119 events total). Of these, 64 were defined as strokes (11 were fatal), and 46, as transient ischemic attacks. Six patients had peripheral embolic events, and 3 patients had valve thrombosis. Kaplan-Meier analysis showed the 25-year freedom from thromboembolic events to be 69% 5% in the AVR group and 52% 8% in the MVR group. Cumulative incidence analysis showed 25-year freedom from thromboembolic events to be and 81% 2% in the AVR group and 70% 3% in the MVR group. Actuarial and cumulative incidence freedom from thromboembolic events is shown in Figure 3. Fig 4. Actuarial and cumulative freedom from bleeding events for aortic valve replacement (AVR) and mitral valve replacement (MVR). Bleeding Events Major bleeding events requiring hospitalization or transfusion occurred in 102 patients in the AVR group and 61 patients in the MVR group. In the AVR group, 51 patients had gastrointestinal bleeding, 23 patients had cerebral bleeding (22 were fatal), 4 patients had cardiac tamponade (two were fatal), 9 patients had internal bleeding, 7 patients had massive epistaxis, 5 patients had leg hematoma, 1 patient had retinal hemorrhage, and 2 patients had hematuria. In the MVR group, 32 patients had gastrointestinal bleeding (2 were fatal), 9 patients had cerebral bleeding (all 9 were fatal), 4 patients had cardiac tamponade (1 was fatal), 6 patients had internal bleeding (1 was fatal), 3 patients had massive epistaxis, 3 patients had leg hematomas, 1 patient had retinal hemorrhage, 1 patient had hematuria, and 2 patients had vaginal bleeding. Actuarial freedom from bleeding complications was 67% 3% at 25 years in the AVR group and 64% 6% in the MVR group. Cumulative incidence analysis showed freedom from bleeding events to be 76% 2% at 25 years and 78% 3% in the MVR group at 25 years. Actuarial and cumulative incidence for freedom from bleeding events are shown in Figure 4. Prosthetic Valve Endocarditis Prosthetic valve endocarditis occurred in 29 AVR patients and 9 MVR patients. For AVR, freedom from PVE was Fig 3. Actuarial and cumulative freedom from thromboembolic events for aortic valve replacement (AVR) and mitral valve replacement (MVR). Fig 5. Actuarial freedom from valve-related mortality and morbidity for aortic valve replacement (AVR) and mitral valve replacement (MVR).

1406 TOOLE ET AL Ann Thorac Surg ST. JUDE MECHANICAL VALVE AT 25 YEARS 2010;89:1402 9 92% 3% (actuarial) and 94% 1% (cumulative incidence) at 25 years. For MVR actuarial freedom from PVE was 97% 1% at 25 years (p 0.013 from AVR) with cumulative incidence being 97% 1% at 25 years. Valve-Related Mortality In the AVR cohort, 54 patients died of valve-related causes: embolism in 14 patients, valve thrombosis in 4 patients, bleeding events in 24 patients, PVE in 7 patients, death related to reoperation for valve re-replacement in 4 patients, and death related to catheterization for perivalvular leak in 1 patient. In addition 45 patients died of unknown causes. In the MVR group 27 patients died of valve-related causes. These were attributable to embolism in 11 patients, bleeding events in 13 patients, PVE in 2 patients, and death related to reoperation for valve re-replacement in 1 patient. Thirty patients died of unknown causes. Kaplan-Meier analysis shows freedom from valverelated deaths to be 66% 8% at 25 years in the AVR group and 87% 3% in the MVR group. Actuarial freedom from valve-related mortality is given in Figure 5. Valve-Related Mortality or Morbidity In the AVR cohort 202 patients had valve-related morbidity or death. At 25 years freedom from valve-related mortality or morbidity was 26% 7%. In the MVR group, 154 patients experienced valve-related morbidity or death. At 25 years freedom from valve-related morbidity or mortality was 29% 6%. Freedom from valve-related morbidity or mortality in the AVR and MVR groups is given in Figure 5. Comment The St. Jude Medical bileaflet pyrolytic carbon mechanical valve was introduced as an alternative to caged ball, tilting disc, and early porcine valves in 1977. It was subsequently tested in clinical trials and received approval from the U.S. Food and Drug Administration in 1982. Our choice for use of this valve while it was still an investigational device owed to structural and hemodynamic concerns about available valve prostheses at the time. Both in vitro and in vivo studies demonstrate low gradients across the valve in both catheterization and echocardiographic evaluations [19, 20]. In our previous reports [1, 2, 7, 11], we have observed, as have others [8 10], the St. Jude Medical mechanical prosthesis is durable (we have observed no structural failures), has excellent hemodynamics, and has a low incidence of thromboembolism. The current study examines 25 years of follow-up and reports our long-term experience with this valve. Prospective annual follow-up of these patients may result in more accurate reporting of complications owing to better patient recall of events than periodic retrospective follow-up. Operative mortality in the current series is 3% in the AVR group and 5% in the MVR group. These results are comparable with those of other long-term studies of this and other prostheses [8 10, 21 24]. As others have previously reported [25, 26], we found decreasing EOAI to be an independent predictor of operative mortality for AVR. Unlike these reports, we did not find EOAI to be an independent predictor of late mortality despite an incidence of severe patient prosthesis mismatch (EOAI 0.65) of 30% in our AVR recipients. Preoperative NYHA class was found to be a more potent predictor of operative death in the AVR group. Both NYHA class and age were independent predictors of operative mortality in the MVR group. These data suggest that preoperative patient characteristics, such as age and cardiac function, may have greater influence on operative mortality than valve-related factors. We found late death to be predicted by age, presence of coronary artery disease, and NYHA class in both AVR and MVR groups. Despite near equal representation in both groups, African American ethnicity was found to be a strong predictor of late mortality in the AVR group but not in the MVR group. That ethnicity was not predictive of late mortality in the MVR group suggests physiologic, as opposed to socioeconomic, factors account for the difference in mortality based on race in the AVR group. Others [27] have shown left ventricular hypertrophy is a more potent predictor of cardiovascular mortality in blacks than whites. The mechanisms for this are not clear. This may suggest inherent ethnic differences in ventricular remodeling after AVR and warrants further investigation. The large difference between overall survival and freedom from valve-related mortality suggests late survival is heavily influenced by non valve-related factors. In the AVR group 20% of deaths were found to be valve-related, and of these, bleeding and thromboembolism accounted for 78%. In the MVR group, 14% of deaths were found to be valve-related, and of these, bleeding and thromboembolism accounted for 89%. Thromboembolism and bleeding together remain the single biggest drawback to mechanical valve replacement. Ideally, appropriate target INRs for AVR and MVR would equally balance the competing risks of bleeding and thromboembolism. We found linearized rates of thromboembolism and bleeding in the AVR group to be 1.9%/patient-year and 3.0%/patient-year, respectively. In the mitral group these rates were 3.2%/patient-year and 2.3%/patient-year, respectively. Linearized rates for bleeding have slowly decreased in both groups. Rates of thromboembolism have been relatively stable and were consistent with those from our last two reports [7, 11]. Based on these relatively balanced end points, we have recommended target INRs of 2 for AVR and 2 to 2.5 for MVR as have other groups [28 30]. These recommendations are at the lower end of the American College of Cardiology guidelines [31] for mechanical AVR and under them for mechanical MVR. An upward trend in thromboembolic events would require that we reexamine these recommendations, but currently they remain stable. International normalized ratio self-management is a strategy that we have not fully explored largely because this task is turned over to the referring physician after hospital discharge. Proponents have reported better

Ann Thorac Surg TOOLE ET AL 2010;89:1402 9 ST. JUDE MECHANICAL VALVE AT 25 YEARS 1407 control of anticoagulation, fewer complications, and improved long-term survival in mechanical valve recipients [32 34]. We observed a near 5%/patient-year linearized rate for the composite end point of thromboembolism and bleeding. Introduction of INR self-management may improve our rates of thromboembolism and bleeding in appropriate patients. Nevertheless, the current rates of bleeding and thromboembolism in conjunction with improved durability of later-generation bioprosthetic valves have caused us, as have others [35, 36], to trend away from the use of mechanical valves. During the 7 years since our last report, 80% of valves implanted were bioprosthetic. The continued, consistent use of mechanical valve replacements in the future will depend on advancements in valve design and anticoagulation strategies associated with less short- and long-term morbidity. The incidence of PVE, similar to that of other series [8 10], has remained low. It affected 5.6% of AVRs (0.6%/patient-year) with a 24% mortality, and 2.3% of MVRs (0.2%/patient-year) with a 22% mortality. Prosthetic valve endocarditis accounted for 13% of valverelated mortality in the AVR group and 7% in the MVR group. As in our previous reports, the vast majority of these cases occurred shortly after surgery. Endocarditis occurring after 5 years was rare. Valve flow characteristics and incorporation of the sewing ring may contribute to this microbial resistance [2, 3]. We have found PVE to be a very serious but fortunately uncommon complication. In summary, the St. Jude mechanical valve remains highly reliable. We observed no structural failures in more than 25 years of follow-up, and reoperation was rare. We have found mortality is more often related to age, cardiac function, and coronary artery disease as opposed to valve-related factors. Because of these attributes the St. Jude Medical mechanical valve remains our mechanical valve of choice. References 1. Crawford FA Jr, Kratz JM, Sade RM, Stroud MR, Bartles DM. Aortic and mitral valve replacement with the St. Jude Medical prosthesis. Ann Surg 1984;199:753 61. 2. Kratz JM, Crawford FA Jr, Sade RM, Crumbley AJ III, Stroud MR. St. Jude prosthesis for aortic and mitral valve replacement: a 10 year experience. Ann Thorac Surg 1993;56:462 8. 3. Arom KV, Nicoloff DM, Kirsten TE, Lindsay WG, Northup WF III. St. Jude Medical prosthesis: valve related deaths and complications. Ann Thorac Surg 1987;43:591 8. 4. Arom KV, Nicoloff DM, Kirsten TE, Northup WF III, Lindsay WG, Emery RW. Ten years experience with the St. Jude Medical valve prosthesis. Ann Thorac Surg 1989;47:831 7. 5. Czer LS, Chaux A, Matloff JM, et al. Ten year experience with the St. Jude Medical valve for primary valve replacement. J Thorac Cardiovasc Surg 1990;100:44 55. 6. Khan S, Chaux A, Matloff JM, et al. The St. Jude Medical valve experience with 1000 cases. J Thorac Cardiovasc Surg 1994;108:1010 20. 7. Zellner JL, Kratz JM, Crumbley AJ III, et al. Long term experience with the St. Jude Medical valve prosthesis. Ann Thorac Surg 1999;68:1210 8. 8. Remadi JP, Baron O, Rousell C, et al. Isolated mitral valve replacement with the St. Jude prosthesis: long term results: a follow up of 19 years. Circulation 2001;103:1542 5. 9. Lund O, Nielsen SL, Arildsen H, Ilkjaer LB, Pilegaard HK. Standard aortic St. Jude valve at 18 years: performance profile and determinants of outcome. Ann Thorac Surg 2000;69:1459 65. 10. Emery RW, Arom KV, Kshettry VR, et al. Decision-making in the choice of heart valve for replacement in patients age 60 70 years: twenty-year follow up of the St. Jude Medical aortic valve prosthesis. J Heart Valve Dis 2002;11(Suppl 1):S37 44. 11. Ikonomidis JS, Kratz JM, Crumbley AK III, et al. Twenty year experience with the St. Jude Medical mechanical valve prosthesis. J Thorac Cardiovasc Surg 2003;126:2022 31. 12. Edmunds LH, Clarke RE, Cohn LH, Miller DC, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac operations. Ann Thorac Surg 1996;62:932 5. 13. Grunkenmeier GL, Lambert LE, Bonchek LI, Starr A. An improved statistical method for assessing the results of an operation. Ann Thorac Surg 1975;20:289 98. 14. Bodnar E, Wain WH, Haberman S. Assessment and comparison of the performance of cardiac valves. Ann Thorac Surg 1982;34:146 56. 15. Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457 81. 16. Grunkenmeier GL, Starr A. The expected lifetime of porcine valves. Ann Thorac Surg 1989;48:317 8. 17. Hosmer DW, Lemeshow S. Applied logistic regression. New York: Wiley, 2000. 18. Cox DR, Oakes D. Analysis of survival data. London: Chapman and Hall, 1984. 19. Emery RW, Nicoloff DM. St. Jude Medical cardiac valve prosthesis: in vitro studies. J Thorac Cardiovasc Surg 1979; 78:269 76. 20. Gray RJ, Chaux A, Matloff JM, et al. Bileaflet, tilting disc and porcine valve substitutes: in vivo hydrodynamic characteristics. J Am Coll Cardiol 1984;3:321 7. 21. Khan SS, Trento A, DeRobertis M, et al. Twenty year comparison of tissue and mechanical valve replacement. J Thorac Cardiovasc Surg 2001;122:257 69. 22. Masters RG, Helou J, Pipe AL, Keon WJ. Comparative clinical outcomes with St. Jude Medical, Medtronic Hall and Carbomedics mechanical heart valves. J Heart Valve Dis 2001;10:403 9. 23. Butchart EG, Li HH, Payne N, Buchan K, Grunkenmeier GL. Twenty years experience with the Medtronic Hall valve. J Thorac Cardiovasc Surg 2001;121:1090 100. 24. Antilla V, Heikkinen J, Biancari F, et al. A retrospective comparative study of aortic valve replacement with St. Jude Medical and Medtronic Hall prostheses: a 20 year follow up study. Scand Cardiovasc J 2002;36:53 9. 25. Blais C, Dumesnil J, Baillot R, Simard S, Doyle D, Pibarot P. Impact of valve prosthesis-patient mismatch on short term mortality after aortic valve replacement. Circulation 2003; 108:983 8. 26. Mohty D, Dumesnil J, Echahidi N, et al. Impact of prosthesispatient mismatch on long term survival after aortic valve replacement. J Am Coll Cardiol 2009;53:39 47. 27. Havranek E, Froshaug D, Emserman C, et al. Left ventricular hypertrophy and cardiovascular mortality by race and ethnicity. Am J Med 2008;121:870 5. 28. Arom KV, Emery RW, Nicoloff DM, Petersen RJ. Anticoagulation related complications in elderly patients with St. Jude mechanical valve prosthesis. J Heart Valve Dis 1996;5:505 10. 29. Horstkotte D, Schulte HD, Bircks W, Strauer BE. Lower intensity anticoagulation therapy results in lower complication rates with the St. Jude Medical prosthesis. J Thorac Cardiovasc Surg 1994;107:1136 45. 30. Hering D, Piper C, Bergeman R, et al. Thromboembolic and bleeding complications following St. Jude Medical valve replacement: results of the German experience with low intensity anticoagulation study. Chest 2005;127:53 9. 31. Bono R, Caraballo B, Chatterjee K, et al. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for management of patients with valvular heart disease. J Am Coll Cardiol 2008;52:1 142.

1408 TOOLE ET AL Ann Thorac Surg ST. JUDE MECHANICAL VALVE AT 25 YEARS 2010;89:1402 9 32. Koertke H, Minami K, Boethig D, et al. INR self management permits lower anticoagulation levels after mechanical heart valve replacement. Circulation 2003;108(Suppl 1):II-75 8. 33. Kortke H, Korfer R. International normalized ratio self management after mechanical heart valve replacement: is an early start advantageous? Ann Thorac Surg 2001;72:44 8. 34. Koetke H, Zitterman, Koefer R. Self management of oral anticoagulation improves long term survival in patients with mechanical heart valve replacement. Ann Thorac Surg 2007;83:24 9. Appendix. Variables Examined for Association With Operative and Late Death 35. Brown J, O Brien S, Wu C, Sihora J, Griffith B, Gammie J. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risk, valve types and outcomes in the Society of Thoracic Surgeon database. J Thorac Cardiovasc Surg 2009;137:82 90. 36. Gammie J, Sheng S, Griffith B, et al. Trends in mitral valve surgery in the United States: results from the society of Thoracic Surgeons adult cardiac surgery database. Ann Thorac Surg 2009;87:1431 7. Operative Mortality Aortic valves Gender Age at operation Body surface area Year of surgery Race Valve size 19 mm Associated CABG Preoperative NYHA class IV Lesion (aortic stenosis) Effective orifice area index Mitral valves Gender Age at operation Body surface area Year of surgery Race Valve size 19 mm Associated CABG Preoperative NYHA class IV Lesion (mitral insufficiency) Ischemic etiology Late Survival Aortic valves Gender Age at operation Year of sugery Race Valve size 21 mm Associated CABG Preoperative NYHA class III/IV Lesion (aortic stenosis) Effective orifice area index Mitral valves Gender Age at operation Year of sugery Race Valve size Associated CABG Preoperative NYHA class III/IV Lesion (mitral insufficiency) Ischemic etiology CABG coronary artery bypass grafting; NYHA New York Heart Association. DISCUSSION DR VINAY BADHWAR (Orlando, FL): As I rise to discuss this fine paper, I wish to disclose that I have spoken at one St. Jude Medical education event in the last 12 months on a practice management topic, yet at no time have I ever had any valve- or product-related relationship that may be construed as conflicting for this discussion. I would like to open with congratulations to Dr Toole on the caliber of his presentation and thank his colleagues at MUSC for furnishing me with an advanced copy of their manuscript, their fifth in their series now, outlining 25 years of experience with the St. Jude mechanical prosthesis in 945 patients. The longevity of a series such as this is a fine rarity in valve surgery that affords us a unique opportunity to not only examine prosthesis durability and function but permits us an insightful glimpse into the validation of our patient selection and surgical decision-making over time. So I have three questions, and these are on anticoagulation, patient selection in your series, and prosthesis selection in your current clinical practice. First, optimal management of chronic anticoagulation remains vexing for all of us, and, in response, there is a growing trend across the country to lower the target INR (international normalized ratio) tolerance for mechanical valves to the lowest end set by recommendations in the 2008 ACCP (American College of Chest Physicians) guidelines. In other words, that is 2.5 for AVR (aortic valve replacement), ranging between 2 to 3, and 3.0 for MVR (mitral valve replacement), ranging from 2.5 to 3.5. However, as stated in your manuscript, in recent years your group has followed this trend by accepting 2.0 for AVR and as low as 2.0 to 2.5 for MVR. In your current report, the thromboembolic complications occurred in 20% of mitral valve patients and 13.6% of aortic valve patients, with 1 out of 5 being fatal. Moreover, your current linearized thromboembolic rates appear to be

Ann Thorac Surg TOOLE ET AL 2010;89:1402 9 ST. JUDE MECHANICAL VALVE AT 25 YEARS 1409 slightly higher than your own 2003 report in the Journal of Thoracic and Cardiovascular Surgery and those reported by Emery in his 2005 25-year series on 4,000-plus St. Jude valve patients. Your practice seems representative of the majority of us who turn over management of warfarin dosing to our referring physicians after a short period of time, and we know the patients are at the greatest risk the more time that they are out of range. Also, we have seen that home monitoring may minimize this. So, given your results, have you readjusted your target INR acceptance, particularly in those that may have other risk factors, and what has been your experience with home monitoring in your management? Second, aortic insufficiency as a primary pathology presenting for AVR is commonly associated with ventricular dilatation and LV (left ventricular) dysfunction at the time of surgical presentation. In your series, one third underwent AVR for primary AI (aortic insufficiency). Was AI examined as a predictor of late mortality, and could you please comment on the use of mechanical versus alternate prostheses in this subset of your current practice? And finally, to paraphrase the lamenting of many mentors, some of whom are in this room, it is believed that the previous eras of valve decision-making based upon large series and longitudinal outcome data seemed to have given way to smaller series and anecdotal reports that become extrapolated into clinical practice. Current trends and prosthesis selection so too reflect what seems to be the current surgical doctrine, one that I admittedly ascribe to, as many of us do, that mechanical valves are the exception, because if it is good for the 75-year-old patient we stretch the logic to think it is probably good for the 55-yearold patient. And based on some exciting but still very anecdotal valve-in-valve evidence, with due respect to our president and his invited lecturer, we then sprinkle in a little salt shaker logic and say, well, in 10 years you might be able to put a percutaneous valve inside your tissue valve. All the while, papers such as yours and others outline excellent multi-decade outcomes on mechanical options while studies such as the Brown paper from Mayo in the April 2008 issue of the Journal of Thoracic and Cardiovascular Surgery clearly show a 5-year survival advantage of mechanical valves over tissue valves in perfectly matched patients less than 65, and, more recently, the European Society of Cardiology taking now the firm step in their recent guidelines to make the formal recommendation at evidence level IIa in favor of mechanical valves in patients less than 65 to 70. So, is your paper providing us with the smelling salts to awaken us into reevaluating prosthesis selection in patients less than 65, and if so, what is the current practice at MUSC? In short, my friend, are you practicing what you preach? I would like to thank the Society for the privilege of discussing this important paper. DR TOOLE: Thank you, Dr Badhwar, for those insightful comments and questions. To deal with the first question concerning anticoagulation and rates of thromboembolism with respect to our current practice of managing anticoagulation, you are right, the majority of these responsibilities are passed on to either the patient s primary care provider or their cardiologist. However, we do set recommendations for them as we send the patient out of the hospital. As far as the rates of thromboembolism, the numbers have fluctuated over the years. Our last report was down significantly from our 15-year report. This report falls more or less in between the two. So, I don t know exactly how significant these fluctuations are. Currently we do run our INR a little bit lower than the numbers you mentioned, and I think in the grand scheme of things we tend to look at the rate of thromboembolism versus the rate of bleeding and try and balance the two. Currently, our freedom from thromboembolism and our freedom from bleeding are pretty close together. I think there is an optimal point between insufficient anticoagulation and overanticoagulation at which bleeding and thromboembolic complications are equally represented. I think we are relatively close to that point now. As far as your second question pertaining to home INR monitoring, we do not currently practice it, but I think that is something that would be worth pursuing. Because a lot of our patient follow-up as far as anticoagulation management takes place outside of our practice, I think it will take some education on our part to have the community buy in. As far as aortic insufficiency goes, we did not stratify those patients separately, and we tend to treat them based on age as far as valve selection goes more so than valvular pathology. And finally, you are correct in that there is a lot of anecdotal information about percutaneous valve-in-valve technology that seems very promising. I think ultimately it would be nice to offer a patient one operation that would fix their valvular problems for the rest of their life. Whether that is insertion of a St. Jude valve or a bioprosthetic valve with a percutaneous tune-up down the road remains to be seen. We are fairly aggressive about pursuing implantation of mechanical valves in patients under 65, provided they don t have comorbidities that would be life limiting. But having said that, our number of St. Jude valve implantations has steadily gone down. Every series that has come out has had a higher percentage of bioprosthetic valves inserted during that time period. I would say that insertion of a St. Jude mechanical valve offers excellent long-term freedom from reoperation; however, the morbidity is staggering. The composite end point of bleeding and thromboembolism as a linearized rate in this series is about 5% per year. In discussing valve selection with a patient, I really leave it up to them and I don t push them too hard in either direction. I have tried not to float the percutaneous valve within a valve as an option because it is something I can t necessarily promise them. DR THORALF SUNDT (Rochester, MN): For mitrals specifically, does your data set include whether or not the subvalvular apparatus was preserved? The beauty of your longitudinal data set over such an extended period of time is that your earlier cases probably didn t have preservation of the subvalvular apparatus. DR TOOLE: That s right. DR SUNDT: If you look at those compared to those in whom the subvalvular apparatus was preserved, do you have any information about survival, ejection fraction, or New York Heart Association class? DR TOOLE: We began preserving the subvalvular apparatus in 1988, but we have not stratified the survival or any of the other parameters you mentioned in this paper, but I think that would be worth doing.