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Ann Thorac Surg 2001;71:S232-S235
© 2001 The Society of Thoracic Surgeons

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Valvular bioprostheses over 15 years

Over twenty-year follow-up of the standard Hancock porcine bioprosthesis implanted in the mitral position

^a Division of Cardiac Surgery, University of Verona Medical School, Verona, Italy
^b Division of Cardiology, University of Verona Medical School, Verona, Italy

Address reprint requests to Dr Santini, Division of Cardiac Surgery, University of Verona Medical School, Piazzale Stefani 1, 37126 Verona, Italy
e-mail: fsant{at}yahoo.com

Presented at the VIII International Symposium on Cardiac Bioprostheses, Cancun, Mexico, Nov 3–5, 2000.

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. To define the long-term results of 331 standard Hancock porcine bioprostheses implanted in the mitral position between 1973 and 1980.

Methods. Of 331 patients (225 male patients, 68%), mean age 49 ± 10 years (range 14 to 69 years), 88% were in New York Heart Association functional class III or IV and 77% were in atrial fibrillation. Follow-up time extended more than 20 years (mean 13.9 years, range 0.3 to 24.7 years) for a total of 4,601 patient-years.

Results. Overall operative mortality was 6.3%. At 5, 10, 15, and 20 years, the actuarial survival rate of patients were 71% ± 2%, 46% ± 3%, 30% ± 3%, and 22% ± 2%, respectively. Actuarial estimates of freedom from structural valve deterioration were 95% ± 1%, 67% ± 3%, 32% ± 3%, and 14% ± 3%; from reoperation were 96% ± 1%, 72% ± 3%, 36% ± 4%, and 18% ± 4%; from thromboembolism were 89% ± 2%, 82% ± 3%, 74% ± 4%, and 51% ± 2%; and from anticoagulant-related hemorrhage were 98% ± 1%, 96% ± 1%, 91% ± 1%, and 86% ± 4%. Estimates of freedom from all valve-related mortality at 5, 10, 15, and 20 years were 89% ± 2%, 76% ± 3%, 64% ± 4%, and 48% ± 4%. Multivariate analysis showed younger age to be a significant risk factor for reoperation. Age at operation did not correlate with structural valve deterioration.

Conclusions. The long-term results with the standard Hancock bioprosthesis implanted in the mitral position appear satisfactory, particularly up to 15 years from implantation. Protection from stroke, anticoagulant hemorrhage, and endocarditis was good.

	Introduction

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For the past 30 years, porcine bioprostheses have been the most widely implanted tissue valve substitutes [1–4]. Despite the well-known disadvantage of these devices such as limited long-term durability, the overall performance of porcine bioprostheses has improved over the years probably as a result of better patient selection, particularly with regard to age, valve design, and tissue preservation methods [3–6].

The goal of this retrospective study was to evaluate the long-term performance of one of the pioneering devices, the standard (glutaraldehyde-fixed) Hancock porcine bioprosthesis (sHPB) (Medtronic Inc, Minneapolis, MN), implanted in the mitral position in patients at the University of Verona, Italy.

	Material and methods

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Over 7 years (between 1973 and 1980), 331 patients (225 male, 68%; male-to-female ratio 2.1:1) with a mean age of 49 ± 10 years (range 14 to 69 years), underwent mitral valve replacement with an sHPB. Forty-six patients (14%) had a previous cardiac operation. Two hundred ninety patients (88%) were in New York Heart Association (NYHA) class III or IV, and 77% were in atrial fibrillation.

The most common indication for mitral valve replacement was rheumatic heart disease (67%). All operations were performed with standard cardiopulmonary bypass and moderate systemic hypothermia. Since 1977, myocardial protection was obtained with topical cooling, with or without coronary perfusion, and with cold potassium cardioplegia. Twenty-five patients (7.5%) underwent an associated procedure (aortic valve replacement, n = 17; coronary artery bypass graft, n = 3; atrial septal defect closure, n = 3; tricuspid valve operation, n = 2). Total bypass time was 65 ± 28 minutes (range 26 to 146 minutes) and the aortic cross-clamp time was 49 ± 18 minutes (range 22 to 130 minutes). The patients’ ages at operation and the valve sizes are reported in Figure 1.

View larger version (21K): [in this window] [in a new window]   Fig 1. Patient population according to arbitrarily defined age groups (A). Prosthetic valves implanted according to size (B).

Patients were followed up directly in our outpatient clinic, mailed questionnaires, or contacted directly by telephone. Data including physical examination, laboratory tests, electrocardiography, and echocardiography were collected at regular intervals. Follow-up was 96% complete, comprising a mean follow-up time of 13.9 years, ranging from 0.3 to 24.7 years, for total of 4,601 patient-years.

Mortality, morbidity, and valved-related complications were reported according to Edmunds and coworkers [7]. All continuous data are presented as mean ± standard deviation. Basic methods of univariate analysis included the ² and Student’s t test. Multivariate (Cox model) proportional hazard regression analysis was used to determine the preoperative risk factors that were significant and the independent predictors of valve-related complications. The factors examined included age, sex, year of operation, valve size, NYHA functional class, congestive heart failure, atrial fibrillation, cross-clamp time, and cardiopulmonary bypass time. Actuarial estimates of morbid events were calculated by the Kaplan–Meier survival analysis method. Values for p of less than 0.05 were considered significant.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
The operative mortality rate was 6.3% (21 cases: cardiac rupture in 4, acute myocardial infarction in 2, multiple-organ failure in 7, stroke in 6, acute renal failure in 1, and mediastinitis in 1). Two hundred one patients (65%) died during the follow-up period (138 cardiac deaths [82 valve-related, 56 nonvalve-related], 40 noncardiac deaths, 23 unknown causes). Long-term survival estimates at 5, 10, 15, and 20 years were 71% ± 2%, 46% ± 3%, 30% ± 3%, and 22% ± 2%, respectively (Fig 2).

View larger version (11K): [in this window] [in a new window]   Fig 2. Long-term actuarial estimates of survival. Number of patients at risk for each time interval is in parentheses.

View larger version (17K): [in this window] [in a new window]   Fig 3. Long-term actuarial estimates of freedom from all valve-related events.

A total of 147 patients (47%) underwent reoperation for any form of valve-related complication (structural valve deterioration in 135, nonstructural valve deterioration in 7, thomboembolic events in 5, and endocarditis in 4), with 14 emergent procedures and 14 deaths (9.5%) (low cardiac output in 7; stroke in 3, acute myocardial infarction in 2, acute renal failure in 1, and major hemorrhage in 1). Actuarial estimates of freedom from this event at 5, 10, 15, and 20 years were 96% ± 1%, 72% ± 3%, 36% ± 4%, and 18% ± 4% (Fig 3). Multivariate analysis showed younger age (p = 0.03, OR = 0.97, SE = 0.04) and heart failure (p = 0.04, OR = 11.53, SE = 1.21) to be significant risk factors for reoperation.

Documented thromboembolic episodes occurred in a total of 60 patients (19%), with 81% of these in chronic atrial fibrillation receiving anticoagulation therapy. These events were fatal in 26 cases (43%). Actuarial estimates of freedom from thromboembolic episodes at 5, 10, 15, and 20 years were 89% ± 2%, 82% ± 3%, 74% ± 4%, and 52% ± 2% (Fig 3). Multivariate analysis showed older age (p = 0.04, OR = 1.04, SE = 0.02) and heart failure (p < 0.005, OR = 1.14, SE = 0.04) to be significant risk factors for this event.

A clinically important bleeding event occurred in 18 patients (6%) and caused death in 8 cases (44%). Actuarial estimates of freedom from this event at 5, 10, 15, and 20 years were 98% ± 1%, 96% ± 1%, 91% ± 1%, and 86% ± 4% (Fig 3). Multivariate analysis showed no significant, independent predictors for this complication in our series.

Prosthetic valve endocarditis developed in 6 patients (2%), with 2 deaths (33%). Four patients required reoperation (1 emergently) and all survived. Actuarial estimates of freedom from this event at 5, 10, 15, and 20 years were 99% ± 1%, 99% ± 1%, 97% ± 1%, and 97% ± 1% (Fig 3). Multivariate analysis showed no significant independent risk factors.

A total of 89 patients had valve-related mortality events (28%). Actuarial estimates of freedom from this outcome (including sudden, unexplained deaths) at 5, 10, 15, and 20 years were 89% ± 2%, 76% ± 3%, 64% ± 4%, and 48% ± 4%. Multivariate analysis showed older age (p < 0.005, OR = 1.04, SE = 0.01) to be a significant independent predictor of valve-related mortality (Fig 4). For any form of valve-related morbidity and mortality event, no significant differences were found in actuarial estimates subdivided according to arbitrarily defined age groups (decades, percentiles).

View larger version (12K): [in this window] [in a new window]   Fig 4. Long-term actuarial estimates of freedom from all valve-related mortality. Number of patients at risk for each time interval is in parentheses.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
The purpose of the present review was to evaluate the long-term clinical performance of the standard sHPB implanted in the mitral position, with special emphasis on the incidence of prosthesis-related complications within the second decade of follow-up. Our operative mortality rate of 6% compares favorably with the data quoted in other series reporting figures between 5% and 10% [1, 3, 6, 8]. This result might be partially related to a relatively low-risk patient population, with only 7.5% of the patients undergoing associated procedures and a reoperation rate as low as 14%. Cardiac rupture was the cause of operative mortality in only 4 patients. Left ventricular posterior wall rupture is a frightful complication that has since been correlated to the high profile of the sHPB implanted in the mitral position [9]. Old patient age and associated procedures did not emerge as significant incremental risk factors for operative mortality in our group.

During the follow-up period, 163 patients developed structural valve deterioration with estimates of freedom from this event at 5, 10, 15, and 20 years of 95% ± 1%, 67% ± 3%, 32% ± 3%, and 14% ± 3%, respectively. Overall sHPB performance clearly declined after the first decade, with a consistent drop at the 13th year of follow-up. In the explanted specimen, primary tissue failure was predominantly caused by cusp calcification with perforation or definite rupture, causing severe valve dysfunction [10]. Structural valve deterioration developed progressively in most of the 163 patients, with 132 elective reoperations and only 3 emergency procedures because of sudden prosthesis failure. These data agree with those in previously reported series [5, 6, 8, 11, 12], with the only exception that overall sHPB performance declined later in our experience, and younger age, year at operation, and sex did not emerge as incremental risk factors in our group.

Nonstructural valve deterioration occurred in 13 patients, and required reoperation in 7 cases, 5 of which were treated emergently. In all cases a paravalvular leak was identified as the cause of morbidity. Since the standard application of the pledget-U-buttressed interrupted suture, the incidence of this complication was sharply reduced.

As previously outlined, structural valve deterioration was the leading cause for reoperation in our experience. Younger age and heart failure emerged as significant predictors of reoperation. As expected and confirmed by other series [5, 6, 12], the decreasing incidence of reoperation with increasing age strongly argues in favor of implanting tissue valves in older patients.

Thromboembolism and bleeding events were infrequent complications (19% and 6%, respectively), consistent with the main advantage of implanting bioprosthetic valves; however, when thromboembolism and bleeding events did occur, both were associated with relatively high casualty rates (43% and 44%, respectively). Older age and heart failure emerged as significant risk factors for thomboembolism, suggesting the need to enhance patient surveillance in this subset, with regard to oral anticoagulation regimens and atrial fibrillation control. Currently, we exclude the atrial appendage in patients with atrial fibrillation regardless of the operation that is performed in the heart.

Prosthetic valve endocarditis appeared as an extremely rare event (2%), with actuarial estimates of freedom at 5, 10, 15, and 20 years of 99 ± 1%, 99 ± 1%, 97 ± 1%, and 97 ± 1%. These data compare favorably with previously reported series [3, 5, 6, 11, 12]. Valve-related mortality, defined as the likelihood of a patient dying of any valve-related complication, including sudden, unexplained early and late death compared with previously reported data [3, 6, 12], occurred in 89 patients (28%). The 15-year estimate of freedom from valve-related mortality event was 64% ± 4%. Multivariate analysis showed older age (p < 0.005) to be a significant independent predictor for this event.

In summary, this study confirms the satisfactory long-term performance of the sHPB implanted in the mitral position, particularly within 15 years of implantation. Structural valve deterioration was confirmed as the leading cause of valve dysfunction with an increasing incidence after the fifth year and a consistent drop of performance at the 13th year of follow-up. Dysfunction occurred progressively and emergency operation due to sudden failure was uncommon. Protection from stroke, bleeding events, and prosthetic endocarditis was rewarding.

	References

Top Abstract Introduction Material and methods Results Comment References

 

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