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Background Mechanical heart valves are durable but thrombogenic, and their use requires that the patient receive anticoagulants. In contrast, bioprosthetic valves are less thrombogenic, but they have limited durability because of tissue deterioration.
Methods To compare the outcomes of patients who receive these two types of valves, we randomly assigned 575 men scheduled to undergo aortic-valve or mitral-valve replacement to receive either a mechanical or a bioprosthetic valve. The primary end points were death from any cause and any valve-related complication.
Results During an average follow-up of 11 years, there was no difference between the two groups in the probability of death from any cause (11-year probability for mechanical valves, 0.57; for bioprostheses, 0.62; P = 0.57) or in the probability of any valve-related complication (0.65 and 0.69, respectively; P = 0.39). There was a much higher rate of structural valve failure among patients who received bioprosthetic valves (11-year probability, 0.15 for the aortic valves and 0.36 for the mitral valves) than among those who received mechanical valves (no valve failures; P<0.001). However, this difference was offset by a higher rate of bleeding complications among patients with mechanical valves than among those with bioprosthetic valves (11-year probability, 0.42 and 0.26, respectively; P<0.001) and by a greater frequency of periprosthetic valvular regurgitation among patients with mechanical mitral valves than among those with mitral bioprostheses (11-year probability, 0.17 and 0.09, respectively; P = 0.05).
Conclusions After 11 years, the rates of survival and freedom from all valve-related complications were similar for patients who received mechanical heart valves and those who received bioprosthetic heart valves. However, structural failure was observed only with the bioprosthetic valves, whereas bleeding complications were more frequent among patients who received mechanical valves.
Methods
Patients
From 1977 through 1982, we randomly assigned 575 men who were scheduled to undergo aortic-valve or mitral-valve replacement (but not both) to receive either a Bjork-Shiley spherical-disk mechanical heart valve or a Hancock porcine-heterograft bioprosthetic valve6,7; randomization took place in the operating room. The study was carried out at 13 participating Veterans Affairs medical centers. The protocol was approved by both a central institutional review board and by the institutional review board at each of the centers. Other criteria for eligibility were that the patient have no history of valve replacement, no active endocarditis, no contraindication to anticoagulation with warfarin, a diameter of 
21 mm for an aortic prosthesis or 27 mm for a mitral prosthesis, and a life expectancy, exclusive of cardiac disease, of three or more years and that the patient give informed, written consent. The 110 patients who received a 21-mm or 23-mm aortic prosthesis were randomly assigned to receive a modified-orifice Hancock porcine heterograft or a Bjork-Shiley valve; 181 received mitral-valve prostheses. The 284 patients who received larger aortic valves were randomly assigned to receive either a standard Hancock bioprosthesis or a Bjork-Shiley valve.
A comparison of the base-line characteristics of the two treatment groups documented the expected similarities between patients assigned to receive the two valve types7. The mean age at entry was 59 ±8 years; 76 percent of the patients (437 of 575) were in New York Heart Association functional class III or IV. Angiographically demonstrable coronary artery disease was present in 44 percent of the patients (247 of 563). All the patients were asked to undergo postoperative cardiac catheterization at six months; the results in the 268 who had the procedure showed no important differences between the two groups in valve gradient, orifice area, or left ventricular function8.
Follow-up
Follow-up data on death, valve-related complications, functional status, and adequacy of anticoagulation were collected at semiannual clinic visits from 1977 through 1985; however, subsequent follow-up data collected by means of a mailed questionnaire and by telephone were limited to the occurrence of death and valve-related complications. All suspected valve-related complications and all deaths were reviewed by a committee blinded to the type of valve for a final determination of whether a valve-related complication had occurred. Only two patients were lost to follow-up, but they were considered to be alive because they have not been identified as having died in searches of two national data bases on deaths, the Department of Veterans Affairs Beneficiary Identification and Records Locator Subsystem and the National Death Index.
Data Analysis
Primary End Points
The two primary end points of this trial were the length of time to death from any cause, including death during surgery (operative mortality), and the length of time to the first occurrence of any of the following nonfatal valve-related complications: systemic embolism, clinically important bleeding, prosthetic-valve endocarditis, valve thrombosis, nonthrombotic valve obstruction, prosthetic valvular regurgitation, and reoperation on the randomly assigned valve for any other reason. The deaths of patients who died suddenly and were not examined at autopsy and those whose cause of death could not be classified were coded as valve-related deaths.
Valve-Related Complications
Prosthetic-valve regurgitation was subdivided into perivalvular regurgitation and central valvular regurgitation, as determined by angiography, during surgery, or at autopsy. To be so classified, prosthetic-valve regurgitation, valve thrombosis, or nonthrombotic valve obstruction had to have been sufficiently severe to result in reoperation or death. The protocol defined clinically important bleeding as bleeding resulting in death; a decrease of 2.0 g per deciliter or more in the hemoglobin concentration, the transfusion of two or more units of blood, or both; intracerebral hemorrhage; gross hematuria leading to hospitalization, urologic manipulation, or cessation of anticoagulation or lasting more than 24 hours; or deep-space hematoma or hemarthrosis leading to hospitalization or disability. Clinically important bleeding occurring within 48 hours of the initial cardiopulmonary bypass was not considered valve-related; otherwise, all bleeding episodes that met the above criteria were classified as valve-related complications. A post hoc analysis was performed in which severe bleeding was defined as that resulting in any one or more of the following: transfusion of three or more units, a 20 percent drop in the hemoglobin level, a hemoglobin level below 7.0 g per deciliter, a new neurologic deficit lasting two days or more, or death9. Structural valve failure was defined as late nonthrombotic valve obstruction or central valvular regurgitation (not occurring at the time of the initial operation).
Statistical Analysis
The Kaplan-Meier estimator of survival10 and the log-rank statistic11 were used to compare the length of time to death and the length of time to the first valve-related complication in the two groups. All P values were two-tailed.
Results
Operative Mortality
Operative mortality was 8 percent (44 of 575) for all patients and 11 percent (26 of 247) for the subgroup with coronary artery disease; there was no significant difference between the study groups according to valve type or location. Coronary artery bypass grafting was performed in 79 percent (194 of 247) of the patients with coronary artery disease; there was no significant difference between the groups with bioprosthetic or mechanical valves in either the operative mortality12 or the late survival of these patients. For patients who received bioprosthetic valves, the probability of death from any cause over the 11-year period was 0.68 for patients with coronary artery disease who underwent bypass grafting and 0.64 for similar patients who did not undergo bypass grafting (P = 0.97). For patients who received mechanical valves the comparable figures were 0.64 and 0.67 (P = 0.89).
Death from All Causes
Primary End Point
There were no significant differences in the first primary end point defined in the protocol, the probability of death from any cause, between patients who underwent replacement of the aortic or mitral valve, with or without coronary artery bypass grafting, according to whether the patients were assigned to receive a bioprosthesis or a mechanical prosthesis (Table 1, Figure 1).
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There were also no significant differences between the groups in the following end points examined in the post hoc analysis: death from all causes for the combined group of patients who received prosthetic aortic or mitral valves (11-year probability for bioprosthetic valves, 0.62; for mechanical valves, 0.57; P = 0.57), deaths from cardiac causes only (11-year probability, 0.48 and 0.41, respectively; P = 0.22), and valve-related deaths only (11-year probability, 0.44 and 0.32, respectively; P = 0.07). Nor were there differences according to the type of valve when the results for patients with and without coronary artery disease were evaluated (11-year probability for patients with coronary artery disease, 0.67 and 0.65, respectively; P = 0.65; for patients without coronary artery disease, 0.52 and 0.48, respectively; P = 0.59).
All Valve-Related Complications
Primary End Point
There were no statistically significant differences between the groups in the second primary end point defined in the protocol, the length of time to the first valve-related complication, whether patients received a mechanical or bioprosthetic valve, with the aortic and mitral positions examined separately (Table 1, Figure 2).
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There were also no significant differences in the length of time to the first valve-related complication when we examined the following post hoc end points: all valve-related complications according to the protocol definition of bleeding for both aortic and mitral valves combined (11-year probability for bioprostheses, 0.69; for mechanical valves, 0.65; P = 0.39); and all valve-related complications according to the post hoc definition of serious bleeding for both valve positions combined (11-year probability, 0.61 and 0.48, respectively; P = 0.17), for aortic-valve replacement (0.54 and 0.44, respectively; P = 0.17), and for mitral-valve replacement (0.75 and 0.58, respectively; P = 0.82).
Individual Valve-Related Complications
Systemic Embolism
There was no significant difference in the occurrence of systemic embolism between patients with bioprostheses and those with mechanical valves in either the aortic position (P = 0.49) or the mitral position (P = 0.61). Fifteen percent (10 of 65) of embolic episodes resulted in death.
Clinically Important Bleeding
There were 155 patients with one or more clinically important bleeding episodes (Figure 3), as defined in the original protocol. Bleeding occurred significantly more frequently among patients with mechanical prosthetic valves, whether we analyzed those who underwent aortic-valve replacement or those who underwent mitral-valve replacement (Table 1); the 11-year probability of bleeding complications for both positions combined was 0.42 for mechanical valves and 0.26 for bioprosthetic valves (P<0.001). Nineteen percent (29 of 155) of bleeding episodes resulted in death. Anticoagulation with warfarin was recorded as being used at one or more of the six-month follow-up visits in 32 percent (63 of 196) of the patients with an aortic bioprosthesis and 63 percent (59 of 93) of those with a mitral bioprosthesis. Atrial fibrillation was present in 43 percent (52 of 122) of the patients with bioprosthetic valves who took warfarin at some time during follow-up. Among bleeding episodes in patients who received warfarin while we were collecting prothrombin-time data (1977 through 1985), the most recent prothrombin-time ratio measured before the bleeding episode was in the specified therapeutic range (2.0 to 2.5 times the control value) in 18 percent (22 of 119) of the episodes, below the therapeutic range in 47 percent (56 of 119), above the therapeutic range in 12 percent (14 of 119), and unknown in 23 percent (27 of 119). According to the therapeutic range that is now recommended (1.5 to 2.0 times control), 24 percent of the patients (28 of 119) would have been classified as having excessive anticoagulation at the time of their bleeding episode.
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Using the post hoc definition of serious bleeding,9 108 patients had one or more such episodes. In 8 of these patients (7 percent) the bleeding episode was associated with a surgical procedure (the original valve replacement in 7 and a tooth extraction in 1); in the cases of the remaining patients, the primary site of bleeding was the gastrointestinal tract in 62 (57 percent), the brain in 18 (17 percent), the urinary tract in 11 (10 percent), muscle or joint in 4 (4 percent), and the nose in 5 (5 percent). Thirty-seven patients required the transfusion of three or more units of blood. The differences in the rate of occurrence of serious bleeding between the patients with bioprosthetic valves and those with mechanical valves remained significant for aortic and mitral positions combined (11-year probability, 0.17 and 0.29, respectively; P<0.001), for patients with an aortic-valve prosthesis (0.18 and 0.26, respectively; P = 0.02), and for patients with a mitral-valve prosthesis (0.16 and 0.38, respectively; P = 0.01).
Prosthetic-Valve Endocarditis
There was no statistically significant difference in the rates of occurrence of prosthetic-valve endocarditis between patients who underwent aortic-valve or mitral-valve replacement with bioprostheses and those who received mechanical valves (Table 1). This was a catastrophic complication with a 43 percent mortality (18 of 42).
Prosthetic-Valve Thrombosis
Prosthetic-valve thrombosis was a rare event with an 11-year probability of 0.01 to 0.02 for patients with either type of valve in either position. The difference between the types of valves was not statistically significant for either position (Table 1). Despite its rarity, this was a frequently lethal event with a mortality rate of 83 percent (5 of 6).
Periprosthetic-Valve Regurgitation
Perivalvular regurgitation occurred significantly more often among patients undergoing mitral-valve replacement with a mechanical prosthesis than among those receiving a bioprosthesis (11-year probability, 0.17 and 0.09, respectively; P = 0.05) (Table 1). Similar differences were seen between the groups among patients undergoing aortic-valve replacement (Table 1).
Structural Valve Failure
In 31 patients, all of whom had bioprostheses, there was structural valve failure (Figure 4). The probability of structural failure at 11 years was 0.15 for patients with an aortic bioprosthesis and 0.36 for patients with a mitral bioprosthesis (P<0.001). The mortality associated with structural valve failure was 39 percent (12 of 31); 5 of the deaths occurred at reoperation.
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The distribution of repeat operations on the randomly assigned prosthetic valve according to the type of valve, its location, and the cause is shown in Table 2. There was a trend (P = 0.07) toward a shorter time to reoperation among patients with aortic bioprostheses than among those with mechanical prostheses; the probability of reoperation at 11 years was 0.16 and 0.07, respectively. This difference was due to reoperation for structural valve failure and to the necessity of changing valves at the initial operation (four patients were randomly assigned to receive a bioprosthetic valve that could not be adequately seated or that obstructed a coronary orifice, necessitating the use of a mechanical valve). There was no significant difference in the probability of reoperation among patients with the two types of mitral prosthesis (P = 0.23). However, there was an accelerating rate of reoperation 10 years or more after valve implantation, so that the probability of reoperation at 11 years was 0.47 for patients with the bioprosthetic mitral valve, as compared with 0.21 for those with the mechanical mitral valve. No significant differences in the proportion of each group that was free of the post hoc combined end point of death, reoperation, or both were observed between the patients with a bioprosthetic valve and those with a mechanical valve for both valve positions combined (11-year probability, 0.68 and 0.59, respectively; P = 0.23), for patients with an aortic prosthesis (11-year probability, 0.63 and 0.56, respectively; P = 0.16), or for patients with a mitral prosthesis (11-year probability, 0.77 and 0.67, respectively; P = 0.86).
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Patients with an Aortic Prosthesis
The difference in the distribution of causes of death between patients with a mechanical aortic-valve prosthesis and those with an aortic-valve bioprosthesis was of borderline statistical significance (P = 0.05). Among patients with a mechanical aortic valve, 38 percent of deaths (38 of 99) were attributed to valve-related complications, 20 percent (20 of 99) to nonvalvular cardiac causes, and 41 percent (41 of 99) to noncardiac causes. Among patients with an aortic bioprosthesis, 50 percent of deaths (51 of 103) were valve-related, 25 percent (26 of 103) were due to nonvalvular cardiac problems, and 25 percent (26 of 103) to noncardiac causes. Only 6 percent of deaths (6 of 103) among patients with an aortic bioprosthesis were due to structural valve failure.
Patients with a Mitral Prosthesis
There was no significant difference in the distribution of causes of death between patients who received mitral bioprostheses and those who received mechanical mitral valves. Among patients with a mechanical mitral-valve prosthesis, 56 percent of deaths (30 of 54) were valve-related, 33 percent (18 of 54) were due to nonvalvular cardiac causes, and only 11 percent (6 of 54) were due to noncardiac causes. Among patients with a bioprosthetic mitral valve, 72 percent of deaths (38 of 53) were valve-related, 21 percent (11 of 53) were due to nonvalvular cardiac causes, and 8 percent (4 of 53) were due to noncardiac causes. Structural valve failure accounted for only 11 percent of the deaths (6 of 53) among patients with mitral bioprostheses.
Discussion
Because the much more frequent occurrence of bleeding in patients with mechanical prostheses offset the higher risk of structural valve failure in patients with bioprosthetic valves, we observed no significant differences between the two study groups in the primary end points of this randomized trial -- namely, the probability of dying from any cause or having any valve-related complication. Because our study population included only middle-aged and older men, these results may not apply to women or to younger men.
A previous study from Edinburgh examined this same question and came to different conclusions5. To compare the results of the Edinburgh Heart Valve Trial with ours, we constructed Figure 5, which shows the 12-year event rates in our trial and the Edinburgh trial5. The probability of death at 12 years was slightly lower in the Edinburgh trial, a difference that probably reflects the younger age of the patients and a lower incidence of coronary artery disease. The 12-year probability of endocarditis and bleeding was greater in our trial than in the Edinburgh trial, whereas the probability of reoperation on a bioprosthetic valve was lower. These differences in event rates between the two trials are unlikely to be due to differences in the definitions of complications. Instead, they are most likely to be explained by differences in the intensity of anticoagulation, the base-line characteristics of the patients7 (for example, younger age and a higher percentage of women increase the probability of structural failure in a bioprosthetic valve3), and possibly the intensity of follow-up surveillance.
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The relatively high rates of bleeding in our study were due largely to the relatively intensive anticoagulant therapy. The recommended prothrombin-time ratio in our protocol -- 2 to 2.5 times the control value -- was consistent with clinical practice in the United States in 1975 and 197618 but higher than the current recommendation of 1.5 to 2.0 times control18,19 and also higher than that used in the Edinburgh Heart Valve Trial. Increasing the prothrombin-time ratio from 1.5 to 2.5 doubles the risk of bleeding19. Anticoagulation control seems not to have been a major factor, since only 12 percent of bleeding episodes were associated with prothrombin-time ratios above the range recommended in the protocol.
Although this trial confirms the limited durability of the bioprostheses, as compared with the mechanical valves, that was found in the Edinburgh trial5 and numerous observational studies,3,13,14,15,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40 this finding must be interpreted in the context of the characteristics of the individual patient and the nature of alternative forms of therapy. The probability of death, valve-related complications, and reoperation did not differ significantly between patients with the two types of valves, because bleeding and periprosthetic regurgitation occurred more frequently in patients with the mechanical prostheses. Furthermore, structural valve failure accounted for only 6 percent of deaths and one quarter of all valve-related complications among patients with aortic bioprosthetic valves, and less than half of all valve-related complications and only 11 percent of the deaths among patients with mitral bioprostheses. The rate of reoperation among the patients with bioprostheses was nearly twice that among the patients with mechanical valves. Because the findings of the Edinburgh Heart Valve Trial, our data, and the results of numerous observational studies indicate that the rate of structural failure of bioprostheses may be accelerating, we plan to follow the patients in our study through 1995.
In our study, mortality at reoperation was approximately 25 percent, which is similar to the 30 percent mortality rate reported for the Edinburgh Heart Valve Trial5 and the 20 percent rate reported by Morishita et al.,37 but higher than the 10 percent rate reported by Bortolotti and colleagues,41 the 8.7 percent rate reported by Pansini and associates,38 or the remarkable 4.7 percent reported by Jones et al34. Over one third of the deaths at reoperation in our study occurred in patients with prosthetic-valve endocarditis; the mortality rate of 50 percent in this group is similar to that in many other reports. The mortality at reoperation among patients without prosthetic-valve endocarditis was 19 percent.
Clinical Implications
Because the overall outcomes of patients who received mechanical or bioprosthetic heart valves were similar after an average follow-up of 11 years, the decision about which type of valve to use should be based on the risks of anticoagulant-related bleeding, structural failure of the bioprosthetic valve, and death at reoperation in each individual patient. Thus, we would favor the use of the bioprosthetic valve in older patients (>60 years of age) who are undergoing aortic-valve replacement, because of the increased likelihood of bleeding among the elderly and the low likelihood of structural failure of the bioprosthesis in the remaining expected life of these patients. Because of the teratogenic effect of warfarin, women who desire to become pregnant should receive a bioprosthesis, provided they are willing to accept a high probability of reoperation 10 years or more after valve replacement. We recommend the use of a mechanical prosthesis for most patients undergoing mitral-valve replacement and for most younger patients ( 
60 years of age), because of the very high risk of structural failure in bioprosthetic mitral valves and because younger patients are more likely to outlive the duration of satisfactory bioprosthetic-valve function. These recommendations may need to be altered if the further follow-up planned for this study (to 15 years) shows that the rate of structural failure of bioprostheses continues to accelerate.
Supported by the Department of Veterans Affairs Medical Research Service, Cooperative Studies Program.
Source Information
From the Cardiology Section, Veterans Affairs Medical Center, and the Department of Medicine, University of Colorado School of Medicine, Denver (K.E.H.); the Cardiothoracic Surgery Section, Veterans Affairs Medical Center, and the Department of Surgery, University of Arizona Health Sciences Center, Tucson (G.K.S.); the Cooperative Studies Program Coordinating Center, Veterans Affairs Medical Center, Hines, Ill. (W.G.H., C.O., T.K.); and the Department of Medicine, Section of Cardiology, University of Southern California, Los Angeles (S.R.). The participants in this study are listed in the Appendix.
Address reprint requests to Dr. Hammermeister at the Cardiology Section (111B), Veterans Affairs Medical Center, 1055 Clermont, Denver, CO 80220.
References
The following persons and institutions participated in the Department of Veterans Affairs Cooperative Study on Valvular Heart Disease (former participants are indicated by an asterisk): Offices and laboratory of the cochairmen: Seattle and Denver -- K.E. Hammermeister (cochairman, medical), J. Heller,* W.M. Hamilton,* C. Burchfiel,* J.L. VanDamme,* C.S. Miller,* S. Kelly,* M.A. Olsen,* R. Firmin,* S. Siefken,* C. Hixson,* B.L. Buck,* S. Stokes,* H. Brandmo,* J. Rathbun,* A. Birdwell, and R. Johnson; Tucson, Ariz. -- G.K. Sethi (cochairman, surgical), M. Garrison,* D. Bunting,* L. Rochester,* and M. Haluja.
Department of Veterans Affairs medical centers, investigators, and supporting personnel: Albany, N.Y. -- G. Bousvaros* and M. Silverman*; Asheville, N.C. -- L. Ramesh,* V. Prokhov,* S.M. Scott, T. Maley, and A. Oakes*; Hines, Ill. -- R.P. Croke,* M. Hwang, P. Rice,* C. Thatcher,* M. White,* and L. Murphy*; Miami -- B.R. Alter,* R. Sequeria,* A. Vargas,* F. Wideman,* R. Chahine,* S. Heyman,* L. Keene,* B. Andritsch,* A. Palomo, and P. Wozniak*; Minneapolis -- G. Pierpont, Y. Sako, M. Park,* M. Johnson,* K. McGregor,* P. Kruse,* and S. Ewald*; Oklahoma City -- E. Schechter, R. Elkins, and D. Noel*; Palo Alto, Calif. -- D. Baim,* N. Robert,* J. Giacomini, D.C. Miller, M. Jamond,* and D. Tovey*; Richmond, Va. -- Z. ul Hassan,* S. Szentpetery, K. Wong,* J. Zierenberg,* and J. Mallory*; San Antonio, Tex. -- B. Groves,* S. Sorensen,* M. Crawford, F. Grover, S. Baca Mancia,* and J. Vittitoe*; San Diego, Calif. -- A. Johnson,* R. Shabetai, W.Y. Moores, G. Dennis,* P. Reilly,* L. Prescott,* and C. McNally Nielsen*; Wadsworth, Calif. -- P. Shah,* M. Wong, J.S. Carey,* J. Witting,* B. Smith,* W. Carnegie,* and N. Sadler*; West Haven, Conn. -- R. Zito,* G. Kopf,* R. Shaw,* M. Cleman,* J. Elesteriades, S. Hashim,* E. Pendergast,* and C. Berman*; West Roxbury, Mass. -- E.D. Folland, S. Khuri, S. Karaffa,* L. Painter,* M. Brew,* and C. Carbone.*
Executive Committee: K.E. Hammermeister and C. Burchfiel, Denver, Colo.; G.K. Sethi, Tucson, Ariz.; J. Souchek, W.G. Henderson, and A. Cantor,* Hines, Ill.; S. Khuri, E.D. Folland, and E.M. Barsamian,* West Roxbury, Mass.; S. Rahimtoola, Los Angeles; W. Hamilton, Seattle; and A. Johnson,* San Diego, Calif.
Death and Complications Subcommittee: F.L. Grover, K.E. Hammermeister, S. Rahimtoola, and G. Sethi.
Cooperative Studies Program Coordinating Center, Hines, Ill.: W.G. Henderson, M. Teutsch,* J. Rowe, J. Souchek,* A. Cantor,* C.A. Oprian, S. Mo,* E. Barnes, C. Harrison, D. Hong,* K. Hur,* T. Kim, M.A. Centanni, M.E. Vitek, W. Armstrong, P. Walther,* D. Zulb, and L. Ulmer.
Special Laboratories, Seattle: Pathology -- D. Reichenbach; Hemolysis -- C. Delaney* and G. Madden.*
Oversight Committees: Operations Committee -- D.R. Labarthe (chairman), W.A. Baxley, P. Meier,* P. Canner, and R.M. Nelson; Human Rights Committee -- E. Hagerty (chairwoman), J. Umbel McKoy,* L. Lawson,* P. Peterson,* E. Perez,* E.M. Butler, D. Hall,* M. Feldbush, H.C. Dudley,* J. Hutchinson,* N. Cahill,* P.J. Moran, W. Upholt,* N. Emanuele, B. Harvey, T.M. Schmid, and J. Stinehelfer.
Central Administration, Cooperative Studies Program: D. Deykin and J. Gold, Boston; and P.C. Huang, Washington, D.C.
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Related Letters:
Outcomes after Heart-Valve Replacement
Bloomfield P., Wheatley D. J., Miller H. C., Hammermeister K.E., Sethi G. K.
Extract |
Full Text
N Engl J Med 1993;
329:1278, Oct 21, 1993.
Correspondence
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