PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation: Part 2: Study results-prostheses, positions, and economic development.

Objectives: The Prospective Randomized On-X Mechanical Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation (PROSE) trial purpose was to investigate whether a current-generation mechanical prosthesis (On-X; On-X Life Technologies/Artivion Inc) reduced the incidence of thromboembolic-related complications compared with a previous-generation mechanical prosthesis (St Jude Medical Mechanical Prosthesis; Abbott/St Jude Medical). This second report documents the valve-related complications by individual prostheses and by Western and Developing populations. Methods: The PROSE trial study was conducted in 28 worldwide centers and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The study protocol, and analyses of 10 demographic variables and 24 risk factors were published in detail in 2021. Results: The total patient population (N = 855) included patients receiving an On-X valve (n = 462) and a St Jude Medical valve (n = 393). The overall freedom evaluation showed no differences at 5 years between the prostheses for thromboembolism or for valve thrombosis. There were also no differences in mortality. There were several differences between Developing and Western populations. The freedom relations at 5 years for mortality favored Western over Developing populations. Valve thrombosis was differentiated by position and site: aortic < mitral (P = .007) and Western < Developing (P = .005). In the mitral position there were no cases in Western populations, whereas there were 8 in Developing populations (P = .217). Conclusions: The On-X valve and St Jude Medical valve performed equally well in the study with no differences found. The only differentiation occurred with valve thrombosis in the mitral position more than the aortic position and occurring in Developing more than Western populations. The occurrence of valve thrombosis was also related to a younger population possibly due to anticoagulation compliance based on record review.

PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation : Part 1(Patient Dynamics): Preoperative demographics and preoperative and operative risk factors.

OBJECTIVES: The PROSE trial purpose is to investigate whether the incidence of thromboembolic-related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.-On-X) compared with a previous generation mechanical prosthesis (St Jude Medical-SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. METHODS: The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. RESULTS: The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. CONCLUSIONS: The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Considerations for prostheses choice in multiple valve surgery.

OBJECTIVES: The prosthesis type for multiple valve surgery (replacement of two or more diseased native or prosthetic valves, replacement of two diseased valves with repair/reconstruction of a third, or replacement of a single diseased valve with repair/reconstruction of a second valve) remains inadequately evaluated. The clinical performance of multiple valve surgery with bioprostheses (BP) and mechanical prostheses (MP) was assessed to compare patient survival and composites of valve-related complications. METHODS: Between 1975 and 2000, 1245 patients had multiple valve surgery (BP 785, mean age 62.0 ± 14.7 years; and MP 460, mean age 56.9 ± 12.9 years). There were 1712 procedures performed [BP 969(56.6%) and MP 743(43.4%). Concomitant coronary artery bypass (conCABG) was BP 206(21.3%) and MP 105(14.1%) (p = 0.0002). The cumulative follow-up was BP 5131 years and MP 3364 years. Independent predictors were determined for mortality, valve-related complications and composites of complications. RESULTS: Unadjusted patient survival at 12 years was BP 52.1 ± 2.1% and MP 54.8 ± 4.6% (p = 0.1127), while the age adjusted survival was BP 48.7 ± 2.3% and MP 54.4 ± 5.0%. The predictors of overall mortality were age [Hazard Ratio (HR) 1.051, p < 0.0001], previous valve (HR 1.366, p = 0.028) and conCABG (HR 1.27, p = 0.021). The actual freedom from valve-related mortality at 12 years was BP 85.6 ± 1.6% and MP 91.0 ± 1.6% (actuarial p = 0.0167). The predictors of valve-related mortality were valve type (BP > MP) (2.61, p = 0.001), age (HR 1.032, p = 0.0005) and previous valve (HR 12.61, p < 0.0001). The actual freedom from valve-related reoperation at 12 years was BP 60.8 ± 1.9% and MP85.6 ± 2.1% (actuarial p < 0.001). The predictors of valve-related reoperation were valve type (MP > BP) (HR 0.32, p < 0.0001), age (HR 0.99, p = 0.0001) and previous valve (HR 1.38, p = 0.008) CONCLUSIONS: Overall survival (age adjusted) is differentiated by valve type over 10 and 12 years and valve-related mortality and valve-related reoperation favours the use of mechanical prostheses, overall for multiple valve surgery.

Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement.

BACKGROUND: The burden oral anticoagulation is a limitation of mechanical valve prostheses. OBJECTIVES: The aim of this study was to test whether patients could be safely managed with dual-antiplatelet therapy (DAPT) (aspirin 325 mg and clopidogrel 75 mg) or lower warfarin after On-X mechanical aortic valve replacement (mAVR). METHODS: PROACT (Prospective Randomized On-X Anticoagulation Trial) (n = 576) is a multicenter (41 sites) noninferiority trial. From June 2006 through February 2014, 201 patients ≥18 years of age without thromboembolic risk factors undergoing mAVR were randomized to receive DAPT (n = 99) or standard warfarin plus aspirin (n = 102) 3 months after mAVR (low-risk arm). From June 2006 through October 2009, 375 patients with 1 or more thromboembolic risk factors were also randomized to lower intensity warfarin plus aspirin (international normalized ratio 1.5 to 2.0; n = 185) or standard warfarin plus aspirin (international normalized ratio 2.0 to 3.0; n = 190) 3 months after mAVR (high-risk arm). RESULTS: The low-risk arm was terminated for excess cerebral thromboembolic events (3.12% per patient-year vs. 0.29% per patient-year, p = 0.02) in the DAPT group at up to 8.8-year follow-up (631.6 patient-years), with no differences in bleeding or all-cause mortality. High-risk arm patients experienced significantly lower major (1.59% per patient-year vs. 3.94% per patient-year, p = 0.002) and minor (1.27% per patient-year vs. 3.49% per patient-year, p = 0.002) bleeding up to 8.7-year follow-up (2,035.2 patient-years), with no differences in thromboembolism (0.42% per patient-year vs. 0.09% per patient-year, p = 0.20) and all-cause mortality. CONCLUSIONS: DAPT was associated with higher rates of thromboembolism and valve thrombosis compared with control in the low-risk arm. International normalized ratios were safely maintained at 1.5 to 2.0 in high-risk patients, without differences in mortality or thromboembolic complications. (Randomized On-X Anticoagulation Trial [PROACT]; NCT00291525).

Conventional aortic valve replacement remains a safe option in patients aged > or = 70 years: a 20-year experience.

BACKGROUND AND AIM OF THE STUDY: Increased life expectancy has resulted in the elderly frequently presenting with severe aortic stenosis. It has therefore become important to define indications for conventional aortic valve replacement (AVR) and transcatheter aortic valve implantation (TAVI) in this patient population. Thus, patients aged > or = 70 years undergoing conventional isolated AVR were evaluated for predictors of early and late mortality. METHODS: A retrospective analysis was conducted of prospectively collected data available from 1,061 consecutive patients (age range: 70-94 years) who underwent isolated AVR between 1982 and 2002. The patient age groups were 70-74 years (n = 466), 75-79 years (n = 367), and > or = 80 years (n = 228). The mean follow up was 6.0 +/- 4.4 years, and the total follow up 6,390 patient-years. Twenty-two variables were considered as potential risk factors for early and late mortality. RESULTS: Early mortality was higher in patients aged > or = 80 years than in those aged 70-79 years. Early mortality in patients aged > or = 80 years was lower between 1998 and 2002 than between 1982 and 1997. Multivariate predictors of early mortality were age > or = 80 years, operative status, previous intervention, renal failure, and mitral regurgitation. The early nonfatal complication rate was similar for patients aged 70-79 years and > or = 80 years, but late mortality was lower between 1998 and 2002 than between 1982 and 1997 in patients aged 70-79 years, and in those aged > or = 80 years. The 10-year actuarial survivals after AVR in patients aged 70-74, 75-79, and > or = 80 years were 54 +/- 3.0%, 43 +/- 3.8% and 17 +/- 3.9%, respectively. Multivariate predictors of late mortality were age 75-79 years, age > or = 80 years, peripheral vascular disease (PVD) and chronic obstructive pulmonary disease (COPD). Female gender was shown to be protective. CONCLUSION: Early mortality was higher in patients aged > or = 80 years undergoing AVR, though this has declined recently and is currently at an acceptable level. Other important predictors of mortality in elderly patients undergoing AVR are operative status, previous interventions, renal failure, mitral regurgitation, male gender, PVD, and COPD. Thus, conventional AVR remains a safe treatment option for the elderly patient.

Medtronic Mosaic porcine bioprosthesis: assessment of 12-year performance.

BACKGROUND: The Mosaic porcine bioprosthesis (Medtronic, Inc, Minneapolis, Minn) was approved in 2000 by the US Food and Drug Administration. Clinical performance was evaluated in 6 centers. METHODS: From 1994 to 2000, 797 patients (mean age 69 years) had aortic valve replacement (AVR) and 232 (mean 67 years) had mitral valve replacement (MVR). Concomitant coronary artery bypass grafting was performed with aortic valve replacement (45.4%) and mitral valve replacement (43.5%). Mean follow-ups were 7.5 years for aortic position and 7.3 years for mitral position. RESULTS: Early mortalities were 2.8% for AVR and 3.0% for MVR. Late mortalities were 4.2%/patient-year for AVR and 5.1%/patient-year for MVR. Overall 12-year survivals were 55.8% ± 3.7% for AVR and 43.9% ± 7.4% for MVR. Twelve-year freedoms from valve-related mortality were 87.1% ± 3.1% for AVR and 82.5% ± 7.7% for MVR. Twelve-year freedoms from reoperation were 84.0% ± 3.3% for AVR and 82.5% ± 7.5% for MVR. Freedoms from structural valve deterioration (SVD) by explant reoperation at 12 years for AVR were 93.3% ± 2.6% for patients at least 60 years old and 75.9% ± 9.3% for patients younger than 60 years. Freedoms from SVD by explant reoperation at 10 years for MVR were 95.3% ± 7.8% for patients at least 70 years old and 84.0% ± 9.3% for patients younger than 70 years. Hemodynamic performance data at 1 year for AVR (sizes 21-27 mm) were mean systolic gradient range 13.7 ± 4.8 to 10.3 ± 3.2 mm Hg and effective orifice area range 1.5 ± 0.3 to 2.5 ± 0.4 cm(2). For MVR (sizes 25-31 mm), data were mean diastolic gradient range 6.7 ± 1.7 to 3.7 ± 0.9 mm Hg and effective orifice area range 1.9 ± 0.3 to 2.4 ± 0.6 cm(2). CONCLUSIONS: Overall performance of Mosaic porcine bioprosthesis to 12 years is satisfactory. Freedoms from SVD by explant reoperation were most satisfactory for aortic position in patients at least 60 years old and mitral position in patients at least 70 years old. Overall actuarial freedom from SVD by explant reoperation is encouraging for patients with MVR.

St Jude Medical Epic porcine bioprosthesis: results of the regulatory evaluation.

BACKGROUND: The St Jude Medical Epic heart valve (St Jude Medical, Inc, St Paul, Minn) is a tricomposite glutaraldehyde-preserved porcine bioprosthesis. The St Jude Medical Biocor porcine bioprosthesis is the precursor valve to the St Jude Medical Epic valve. The Epic valve is identical to the Biocor valve except that it is treated with Linx AC ethanol-based calcium mitigation therapy. METHODS: The St Jude Medical Epic valve was implanted in 761 patients (mean age 73.9 ± 9.2 years) between 2003 and 2006 in the US Food and Drug Administration regulatory study in 22 investigational centers. The position distribution was 557 aortic valve replacements, 175 mitral valve replacements, and 29 double valve replacements. Concomitant coronary artery bypass grafting was performed in 50.8% of patients undergoing aortic valve replacement and 36.6% of those undergoing mitral valve replacement. RESULTS: The early mortality was 3.6% in aortic and 2.3% in mitral valve replacement. The follow-up was 1675.5 patient-years with a mean of 2.2 ± 1.2 years/patient. Late mortality was 5.2%/patient-year in aortic and 6.6%/patient-year in mitral valve replacement. The late major thromboembolism rate was 0.98%/patient-year for aortic and 2.6%/patient-year for mitral valve replacement. There were 19 reoperations, including 2 for structural valve deterioration, 1 for thrombosis, 9 for nonstructural dysfunction, and 7 for prosthetic valve endocarditis. The actuarial freedom from reoperation owing to structural valve deterioration for aortic valve replacement at 4 years for age 60 years or less was 93.3% ± 6.4%; for ages 61 to 70 years, 98.1% ± 1.9%; and for older than 70 years, 100% (P = .0006 > 70 vs ≤ 60 years). There were no events of structural deterioration with mitral valve replacement. The actuarial freedom from major thromboembolism for all patients at 4 years was 93.6% ± 1.0%. The 2 cases of structural valve deterioration occurred in aortic valves that became perforated without calcification causing aortic regurgitation. CONCLUSIONS: The performance of the St Jude Medical Epic porcine bioprosthesis is satisfactory at 4 years for both aortic and mitral valve replacement. This study establishes the early clinical performance including durability of this porcine bioprosthesis.

Influence of patient gender on mortality after aortic valve replacement for aortic stenosis.

OBJECTIVE: To assess the influence of gender on mortality after aortic valve replacement for aortic stenosis. METHODS: A retrospective analysis was performed on data prospectively collected from all patients undergoing aortic valve replacement for aortic stenosis. Multivariate regression analysis was performed to evaluate the effect of 22 preoperative and operative variables on early, late, and overall mortality. RESULTS: Aortic valve replacement was performed in 3343 patients with aortic stenosis between 1982 and 2003. The female patients were older, with a smaller body mass index. The women were less likely to have diabetes, chronic obstructive pulmonary disease, previous myocardial infarction, or left ventricular ejection fraction <35% but were more likely to have hypertension or a New York Heart Association III-IV classification. The female patients received a smaller prosthetic valve, with a smaller effective orifice area index (EOAI). The mean follow-up period was 6.18 ± 4.96 years, with a total of 2066.142 years of follow-up. The independent predictors of early mortality for the male patients included age, concomitant surgical revascularization, congestive heart failure, and valve size of ≤21 mm. The independent predictors of late mortality for the male patients included age, concomitant surgical revascularization, diabetes, renal failure, chronic obstructive pulmonary disease, congestive heart failure, and a bioprosthetic valve. The independent predictors of overall mortality for the male patients included age, concomitant surgical revascularization, diabetes, renal failure, heart failure, and valve size of ≤21 mm. For the female patients, the risk factors for early mortality included body mass index <25 kg/m(2); for late mortality included age, concomitant surgical revascularization, New York Heart Association class III-IV, and diabetes; and for overall mortality included age, concomitant surgical revascularization, New York Heart Association class III-IV, and renal failure. Furthermore, male gender was an independent predictor of late (but not early or overall) mortality. CONCLUSIONS: The independent predictors of mortality after aortic valve replacement for aortic stenosis differed between the male and female patients. Male gender increased the risk of late mortality, and a valve size of ≤21 mm increased the risk of early and overall mortality among the male patients only. These differences need to be taken into consideration preoperatively and require consideration during operative management.

Update on technologies for cardiac valvular replacement, transcatheter innovations, and reconstructive surgery.

Since the 2006 Surgical Technology International monograph on valvular prostheses, there have been significant developmental and investigative advances, particularly for transcatheter implantation. Aortic bioprostheses and mechanical prostheses continue to incorporate design changes to optimize hemodynamics and prevent prosthesis-patient mismatch and to have a potential satisfactory influence on survival. There have been continual technological improvements striving to bring forward advances that improve the durability of bioprostheses and reduce the thrombogenicity of mechanical prostheses. There also has been a continuance to preserve biological tissue with glutaraldehyde, rather than clinically evaluate other cross-linking technologies, by controlling or retarding calcification with therapies to control phospholipids and residual aldehydes. The techniques of mitral valve reconstruction have now been well established, and annuloplasty rings have been designed for the potential of maintaining the anatomical and physiological characteristics of the mitral annulus. There has been limited advancement in the past four years for interventional annuloplasty, for remodeling of the length and shape of the dilated annulus, prevention of dilatation of the annulus, and support for the potentially fragile area after partial-leaflet resection. Currently, there continues to be emergence of catheter-based therapies, particularly for management of aortic stenosis but not mitral regurgitation. For management of selected populations with critical aortic stenosis, the techniques for aortic valve substitution have had further advancement for retrograde catheter techniques, as well as apical transventricular implantation. There has not been significant advancement during the past four years to address mitral regurgitation by experimental transcoronary sinus, stent-like devices and transventricular, edge-to-edge leaflet devices. The devices, descriptions, and pictorial images comprising this monograph have been limited to technologies that are considered to be predominant, at least for the immediate duration. The general purpose of the monograph is to serve as an educational document.

Influence of the On-X mechanical prosthesis on intermediate-term major thromboembolism and hemorrhage: a prospective multicenter study.

OBJECTIVES: Long-term thromboembolic and hemorrhagic outcomes after mechanical valve replacement have been well described; however, few studies have described these outcomes after valve replacement with the On-X mechanical prosthesis (On-X Life Technologies, Inc, Austin, Tex). METHODS: Between 2003 and 2008, 737 patients underwent either aortic valve replacement (n = 400), mitral valve replacement (n = 282), or double-valve replacement (n = 55). Longitudinal performance, freedom evaluation, and risk analysis were assessed with regard to major thromboembolism and hemorrhage. Risk modeling was performed with 16 variables inclusive of age, atrial fibrillation, concomitant coronary artery bypass grafting, New York Heart Association class, and ventricular dysfunction. RESULTS: Early mortality was 2.5% (n = 10) for aortic valve replacement and 3.2% (n = 9) for mitral valve replacement. Late mortality for aortic valve replacement was 4.8% per patient-year and 6.0% per patient-year for mitral valve replacement. Five-year freedom from major thromboembolism was 96.5% ± 1.2% for aortic valve replacement and 97.7% ± 0.9% for mitral valve replacement. Five-year freedom from hemorrhage was 93.6% ± 1.8% for aortic valve replacement and 95.7% ± 1.5% for mitral valve replacement. Concomitant coronary artery bypass grafting was predictive of major thromboembolism after aortic valve replacement (hazard ratio, 5.3; P = .02) and antithrombotic hemorrhage after mitral valve replacement (hazard ratio, 4.7; P = .03). No other independent predictors of major thromboembolism or hemorrhage were identified. One thrombosed mitral prosthesis was observed after deliberate discontinuation of anticoagulation. The major thromboembolic events occurred with variation of international normalized ratio levels inclusive of subtherapeutic levels. The majority of hemorrhagic events occurred with high international normalized ratio levels. CONCLUSIONS: The On-X mechanical prosthesis provides favorable intermediate-term results with regard to major thromboembolism and hemorrhage.

Transapical transcatheter aortic valve implantation: follow-up to 3 years.

BACKGROUND: We performed the first human case of successful transapical transcatheter aortic valve implantation on a beating heart in October 2005, and therefore we have the longest follow-up on transapical aortic valve implantation in humans. We now report clinical and echocardiographic outcomes of transapical aortic valve implantation in 71 patients. METHODS: Between October 2005 and February 2009, 71 patients (44 female) underwent transcatheter transapical aortic valve implantation with either 23- or 26-mm Edwards Lifesciences transcatheter bioprostheses. All patients with symptomatic aortic stenosis were declined for conventional aortic valve replacement owing to unacceptable operative risks and were not candidates for transfemoral aortic valve implantation because of poor arterial access. Clinical and echocardiographic follow-ups were performed before discharge, at 1 and 6 months, and then yearly. The mean follow-up was 12.9 +/- 11.5 months with a total of 917.3 months of follow-up. RESULTS: Mean age was 80.0 +/- 8.1 years and predicted operative mortality was 34.5% +/- 20.4% by logistic EuroSCORE and 12.1% +/- 7.7% by The Society of Thoracic Surgeons Risk Calculator. Valves were successfully implanted in all patients. Twelve patients died within 30 days (30-day mortality: 16.9% in all patients, 33% in the first 15 patients, and 12.5% in the remainder), and 10 patients died subsequently. Overall survival at 24 and 36 months was 66.3% +/- 6.4% and 58.0% +/- 9.5%, respectively. Among 59 patients who survived at least 30 days, 24- and 36-month survivals were 79.8% +/- 6.4% and 69.8% +/- 10.9%, respectively. Late valve-related complications were rare. New York Heart Association functional class improved significantly from preoperative 3.3 +/- 0.8 to 1.8 +/- 0.8 at 24 months. The aortic valve area and mean gradient remained stable at 24 months (1.6 +/- 0.3 cm(2) and 10.3 +/- 5.9 mm Hg, respectively). CONCLUSION: Our outcome suggests that transapical transcatheter aortic valve implantation provides sustained clinical and hemodynamic benefits for up to 36 months in selected high-risk patients with symptomatic severe aortic stenosis.

Hemodynamic performance of mitroflow aortic pericardial bioprosthesis - optimizing management for the small aortic annulus.

BACKGROUND: Documentation of the hemodynamics of the Mitroflow aortic pericardial bioprosthesis has been incomplete. The aim of the study was to provide reference effective orifice areas for the implant calculation of effective orifice area indexes to avoid prosthesis-patient mismatch. METHODS: Echocardiograms were evaluated in 55 patients (39 females, 16 males), mean age 77.0 +/- 6.9 years (range 51-90 years). The mean time of the studies was 11.0 months. The prosthesis sizes and numbers evaluated were 19 mm (n = 13), 21 mm (n = 19), 23 mm (n = 13) and 25 mm (n = 10). RESULTS: Peak aortic velocities averaged from 2.2 to 2.7 m/sec, mean gradients from 10.6 to 15.1 mmHg, peak gradients from 20.7 to 29.7 mmHg, and effective orifice area (EOA) from 1.4 to 1.8 cm (2). When accounting for the subaortic velocity, mean gradients averaged from 7.5 to 10.0 mmHg, and peak gradients averaged 15.1 to 23.5 mmHg. The effective orifice area indexes ranged from 0.8 to 1.0 cm (2)/m (2). The mean postoperative left ventricular mass index was 101.6 gm/m (2). CONCLUSIONS: The IN VIVO effective orifice areas by valve size of the Mitroflow aortic pericardial bioprosthesis provide the opportunity of avoiding obstructive characteristics for all valve sizes, including optimizing the management of the small aortic annulus.