EJCTS Click here to go to Edwards website
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Robert T. Miyagishima
Gary L. Grunkemeier
Guy J. Fradet
Samuel V. Lichtenstein
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jamieson, W.R. E.
Right arrow Articles by Lichtenstein, S. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jamieson, W.R. E.
Right arrow Articles by Lichtenstein, S. V.

Eur J Cardiothorac Surg 1999;15:786-794
© 1999 Elsevier Science NL

Bileaflet mechanical prostheses performance in mitral position

W.R. Eric Jamieson, Robert T. Miyagishima, Gary L. Grunkemeier, Eva Germann, Charmaine Henderson, Guy J. Fradet, Lawrence H. Burr, Samuel V. Lichtenstein

St. Paul's Hospital-Heart Center, Vancouver General Hospital, University of British Columbia, Vancouver, Canada

Received 27 October 1998; received in revised form 8 February 1999; accepted 16 February 1999.

Corresponding author. Department of Surgery, 3100-910 West 10th Avenue, Vancouver, Canada V5Z 4E3, Canada Tel.: +1-604-875-4141; fax: +1-604-875-4036


   Abstract
Top
 Abstract
1. Introduction
2. Patient population
3. Methods and statistical...
 4. Results
5. Discussion
References
 
Objective: The experience with the Carbomedics (CM) and the St. Jude Medical (SJM) bileaflet mechanical prostheses was evaluated to determine thromboembolic and hemorrhagic complications and predictive risk factors. Methods: From 1989 to 1994, a total of 625 patients had mitral valve replacement (CM, 240; SJM, 385); 32.5% (203), concomitant procedures and 32.8% (205), previous cardiac surgery, primarily valve replacement procedures. Results: The pre-operative variables did not distinguish the populations, except for previous surgery CM 37.9% and SJM 29.6% (P<0.05). The pre-operative variables (type of prostheses, cardiac rhythm, coronary artery bypass, NYHA III/IV, advancing age, gender, urgency status and previous surgery) were not predictive of overall thromboembolism (TE), major TE, minor TE, prosthesis thrombosis and hemorrhage (P not significant; P=NS). The linearized rate of total TE events for overall MVR was 5.0%/patient-year (CM 4.4; SJM 5.4). The <=30 day major crude rate was 0.44%, while the >30 day late major event rate was 2.0%/patient-year. Of the total TE events 91% of <=30 days and 75%, >30 days had an INR <2.5 at or immediately prior to the event. The thrombosis rate (included in TE events) was 0.63%/patient-year (ten events, four managed successfully with thrombolysis, five successfully with reoperation, and one fatality identified at autopsy). The freedom, at 5 years, from major/fatal TE, thrombosis and hemorrhage from anticoagulation was 88.2%, and 89.5% exclusive of early events. Conclusions: This non-randomized prospective observational evaluation of the CarboMedics and St. Jude Medical prostheses has not revealed any differentiation in performance of the prostheses. The study serves as a single institution experience with the potential for future comparative evaluation.

Key Words: Mechanical prostheses • Mitral position • Thromboembolism


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patient population
3. Methods and statistical...
 4. Results
5. Discussion
References
 
There has been a choice of mechanical prostheses and bioprostheses as valvular substitutes for cardiac valve replacement surgery for 25 years. The first mechanical prosthesis, the Starr–Edwards caged-ball valve (Baxter Healthcare Irvine, CA) was introduced 37 years ago. The developments in mechanical prostheses have been monoleaflet and bileaflet designs, both formulated with pyrolytic carbon in whole or in part. The developments over the past two decades have been introduced to reduce or eliminate valve-related complications, namely thromboembolism and thrombosis, anticoagulant-related hemorrhage and structural failure, as well as to optimize hemodynamic performance [1–29]. The St. Jude Medical mechanical prosthesis (St. Jude Medical, Minneapolis, MN) was introduced in 1977 as the first bileaflet pyrolytic carbon mechanical prosthesis. The St. Jude Medical prosthesis has been the most widely implanted mechanical bileaflet prosthesis [2–4,9–12,14–20,23]. There have been three other bileaflet mechanical prostheses which have reached clinical application: Hemex-Duromedics, now Tekna (Baxter Healthcare, Irvine, CA), Sorin Bicarbon (Sorin, Saluggia, Italy) or Baxter Mira (Baxter Healthcare, Irvine, CA) and CarboMedics (Sulzer–CarboMedics, Austin, TX). The CarboMedics mechanical prosthesis was introduced in 1986 and the clinical investigation resulted in formal approval by the Food and Drug Administration of the United States in 1993.

The CarboMedics mechanical prosthesis has an increasing number of published clinical studies [5,8,13,22,24–27]. The documentation on the St. Jude Medical prosthesis has been very extensive [2–4,9–12,14–20,23]. There has been no randomized or non-randomized trials comparing the clinical performance of bileaflet prostheses. The purpose of this communication is to document the performance of the bileaflet mechanical prostheses, St. Jude Medical and CarboMedics, in a prospective non-randomized study evaluating the overall experience with the prostheses in mitral replacements and to determine predictors of performance.

The St. Jude Medical and CarboMedics mechanical prostheses have distinct differentiating characteristics. The St. Jude Medical prosthesis has pyrolytic carbon over graphite substrate for both housing and leaflets. The leaflets are flat and impregnated with tungsten for radiopacity in special three-axis radiographic views. The CarboMedics, on the other hand, has a solid Pyrolite® carbon housing and flat leaflets of Pyrolite® carbon coated over tungsten loaded graphite substrate. The prosthesis has excellent radiopacity with the radiopaque titanium stiffening ring and increased tungsten content of the leaflet substrate.

The leaflets of the St. Jude Medical prosthesis are orifice oriented and closing forces are supported by the pivot system. The pivot ears are raised above the housing and leaflet motion is by rotation. The CarboMedics prosthesis, on the other hand, has the leaflet pivot retention mechanism within the housing without pivot guards, struts or orifice projections. Leaflet motion with the CarboMedics prosthesis is also by rotation.

The CarboMedics prosthesis has a titanium stiffening ring which prevents deformation of the valve orifice but facilitates rotation of the valve within the sewing ring. The St. Jude Medical prosthesis which as originally introduced was not rotatable. The newly introduced St. Jude Medical Masters series is rotatable but was not utilized in this study interval. For the small aortic annulus both prostheses manufacturers have introduced special versions to support optimization of hemodynamics–the St. Jude Medical Hemdynamic Plus (HP) and the CarboMedics TopHat prostheses. Both of these prostheses are designed with minimization of the external valve diameter.


   2. Patient population
Top
 Abstract
 1. Introduction
2. Patient population
3. Methods and statistical...
 4. Results
5. Discussion
References
 
From September 1989, the time of commencement of the University of British Columbia in the United States - Food and Drug Administration CarboMedics investigational study, to June 1994 the CarboMedics (CM) and St. Jude Medical (SJM) prostheses were evaluated in a non-randomized prospective study. The prosthesis selection was at the discretion of the surgeon.

Mitral valve replacements were performed in 625 patients (male, 257; female, 368). The mean age of the population was 58.5±12.1 (SD) years (range 22–82 years). There were 54.7% NYHA Class III and 22.7% Class IV patients. Of the 625 patients, 317 (59.4%) were in atrial fibrillation preoperatively. The mean follow-up was 2.52±1.57 (SD) years, a total of 1576.3 years. The completeness of follow-up was 99.0%.

Concomitant procedures were performed in 32.5% (203) of the patients, coronary artery bypass in 22.9% (143) of the patients. Of the total population, 32.8% (205) had previous cardiac procedures, primarily valve replacement procedures. There was a preponderance of patients with previous operations in the CM group (37.9% versus 29.6% for SJM) (P<0.05) (Table 1). The patient populations for MVR for the CM and SJM groups were otherwise essentially the same considering the incidence of coronary artery bypass, atrial fibrillation, concomitant procedures, valve pathology and status of procedures (P=NS).


View this table:
[in this window]
[in a new window]
  		Table 1. Comparison of groupsa

 
The CM was implanted in 240 patients (male, 91; female, 149) and the SJM in 385 patients (male, 166; female, 219) in mitral valve replacements (MVR). The mean age of the MVR-CM population was 59.8±11.8 (SD) years (range 24–82 years) and of the SJM population, 57.7±12.2 (SD) years (range 22–81 years) (P=NS). The MVR-CM patients were 56.3% NYHA class III and 22.5% class IV, while for SJM patients, 53.8% and 22.9%, respectively (P=NS). The mean follow-up for the MVR-CM was 2.64±1.54 (SD) years (total 535.1 years) and for SJM was 2.45±1.59 (SD) years (total 925.6 years). The completeness of follow-up was 99.2% and 99.0%, respectively.


   3. Methods and statistical analysis
Top
 Abstract
 1. Introduction
2. Patient population
3. Methods and statistical...
4. Results
5. Discussion
References
 
The ‘Guidelines for Reporting Morbidity and Mortality after Cardiac Valvular Operations’ were used for definitions of valve-related complications, categorization and statistical methods [30]. The recommended definitions of thromboembolic and hemorrhagic events proposed by Bodnar et al. [31] in the article entitled ‘Proposal for Reporting Thrombosis, Embolism and Bleeding after Heart Replacement ’ have been incorporated in the evaluation. The thromboembolic and hemorrhagic complications have been categorized by these authors, as follows:

  1. valve thrombosis,
  2. cerebrovascular accident as occlusive (ischemic) or hemorrhage in origin, in terms of transient ischemic attack (<24 h), reversible ischemic neurological deficit (RIND-minor stroke) (>72 h with complete resolution within 3 weeks), major stroke,
  3. systemic (non-cerebral) embolism,
  4. systemic (non-cerebral) bleeding.

The information on valve-related complications for this study was obtained by direct contact with patients, family physicians, consultants, hospital health records, and official death registries over a closing interval of 6 months in 1995.

The valve-related complications and composite indexes of these valve-related complications were evaluated in the time-related manner by actuarial life-table techniques (Cutler–Ederer method). The Wilcoxon–Gehan statistic was used to provide comparison of complication-free curves. Linearized occurrence rates (events per 100 patient-years or percent per patient-year) were utilized specifically for documenting thromboembolic and hemorrhagic complications. Overall thromboembolic and hemorrhagic rates encompass early events (<=30 days) and late events (>30 days). Late events are expressed separately from the overall events. Hazard function evaluations are demonstrated for thromboembolic and hemorrhagic complications, and valve-related mortality and reoperation for the overall population groups. The predictors of early mortality were determined by logistic regression and the predictors of late mortality and thromboembolism by the Cox proportional hazard regression model (SPSS statistical package V6.1). The parameters evaluated were prosthesis types, cardiac rhythm, coronary artery bypass surgery, NYHA III/IV, advancing age, gender, urgency status and previous valvular surgery. The hazard functions for thromboembolism, thromboembolism and hemorrhage, reoperation and valve-related mortality are expressed at intervals of 6 months.


   4. Results
Top
 Abstract
 1. Introduction
2. Patient population
3. Methods and statistical...
 4. Results
5. Discussion
References
 
The early mortality for the total population of mitral valve replacements was 6.7% (42 events) (CM, 5.4%; SJM, 7.5%). There were two (4.8%) valve-related deaths while cardiac causes were 40.5% (17) and non-cardiac causes and surgical causes were 55% (23). The risk factors of early mortality were NYHA III/IV (odds ratio 3.5, P=0.0002) and previous cardiac procedures (odds ratio 4.6, P=0.033).

The overall mortality and mortality from valve-related complications are detailed in Table 2 for the overall population (including the 95% confidence limits) and by the prosthesis types.


View this table:
[in this window]
[in a new window]
  		Table 2. Mortality and mortality from valve-related complications (overall)a

 
The mortality (early and late valve-related) for the overall patient population was 3.0%/patient-year (47) (CM 2.8 and SJM 3.1%/patient-year). The valve-related rate of late mortality was 0.63%/patient-year. There were three deaths due to major thromboembolism, one due to prosthesis thrombosis and four due to hemorrhage. The risk factors of late mortality were male gender (odds ratio 2.00, CL 1.1–3.6, P=0.02), previous cardiac operations (odds ratio 3.32, CL 0.99–11.08, P=0.05) and NYHA III/IV (odds ratio 1.98, CL 1.05–3.73, P=0.03). The patient survival, at 5 years, was 79.9±2.5%.

The valve-related complications are summarized in Table 3 for overall mitral valve replacement and by prosthesis types (CM and SJM). The freedom from valve-related mortality, excluding early mortality and sudden unexpected deaths was, at 5 years, 97.9±0.7%.


View this table:
[in this window]
[in a new window]
  		Table 3. Valve-related complications (overall and late)a

 
The experience from valve-related reoperations for MVR is shown in Table 4. There were two fatalities from 21 reoperations, reoperative mortality 9.5%. The freedom from reoperation for the overall population was 97.5±0.8% at 3 years and 91.8±2.4% at 5 years.


View this table:
[in this window]
[in a new window]
  		Table 4. Valve-related reoperationa

 
The major consideration of this clinical report is the assessment of thromboembolic complications. Tables 3 and 4 detail thromboembolic and hemorrhagic complications for the overall MVR population but also by the prosthesis-types (CM and SJM). The incidence of total thromboembolic events was 5.0%/patient-year, a total of 79 events (Table 3). The linearized rate for minor events was 2.5%/patient-year (40) and for major events including thrombosis was 2.5%/patient-year (39). There were ten thrombotic events or 0.6%/patient-year. There were no risk factors, inclusive of prosthesis-types and cardiac rhythm, of thromboembolic events, whether considered for overall, major, minor or thrombosis and overall with exclusion of early events (P=NS).

The thromboembolic events and major anticoagulant complications have been considered for two time intervals, <=30 days and >30 days (Table 5). The overall major events (>30 days) (major, reversible, thrombosis and fatal) was 2.0%/patient-year. The linearized rate of overall hemorrhage was 1.5%/patient-year. Of the 625 patients the number of major events > 30 days were two major TE reversible, 18 major TE permanent, three systemic TE major, nine thrombosed prostheses and of the total, three fatalities. There were 23 overall hemorrhagic events with four fatalities requiring hospitalization or outpatient blood transfusions. There were, within the hospital or early period <=30 days, six major thromboembolic events, a rate of 1.0%, with one fatality, 0.2%, and one non-fatal thrombosis event, 0.2%. The early hemorrhagic rate (non-fatal) was also 0.2%, one event.


View this table:
[in this window]
[in a new window]
  		Table 5. Thromboembolic and hemorrhagic events >30 days(late) and <=30 days (early)a

 
Figs. 1 and 2 illustrate the freedom for MVR of thromboembolic and hemorrhagic events overall and exclusive of early events (<=30 days). The figures show the freedoms from major thromboembolism, and overall major/fatal thromboembolism, thrombosis and hemorrhagic events. The freedom from major thromboembolism was, at 5 years, 91.5±1.8% and 92.7±1.7% with exclusion of early events (Fig. 1). The freedom from thrombosis was, at 5 years, 96.2±1.5% and 96.4±1.5% with exclusion of early events. The assessment of overall thromboembolic and hemorrhagic events (Fig. 2) revealed 5 year freedom of 88.2±1.9% and 89.5±1.9% with exclusion of early events.



View larger version (23K):
[in this window]
[in a new window]
  		Fig. 1. Mitral valve replacement – freedom from major thromboembolism overall and with exclusion of early events.

 


View larger version (23K):
[in this window]
[in a new window]
  		Fig. 2. Mitral valve replacement – freedom from major/fatal TE, thrombosis and hemorrhage overall and with exclusion of early events.

 
The hazard rates of overall thromboembolic and hemorrhagic events are demonstrated in Fig. 3. The hazard rates of valve-related mortality and reoperation, including mortality from reoperation are illustrated in Fig. 4.



View larger version (36K):
[in this window]
[in a new window]
  		Fig. 3. Mitral valve replacement – hazard function of thromboembolic and hemorrhagic events.

 


View larger version (31K):
[in this window]
[in a new window]
  		Fig. 4. Mitral valve replacement – hazard function of valve-related mortality and reoperation.

 
The anticoagulant status of patients who experienced thromboembolic events at the various time intervals was determined. The four thromboembolic events in hospital with MVR were all anticoagulated at an INR of <2.5 at or immediately prior to the event. There were 75 MVR post-hospital events and 76% were inadequately anticoagulated. Of the 79 events, 11 events occurred in the time period <=30 days and 91% had an INR <2.5. There were 68 events occurring at >30 days and 75% had an INR <2.5. The rhythm at the time of the events was atrial fibrillation, 33% and normal sinus rhythm, 67%.

There were ten episodes (CM, 6; SJM, 4) of prosthesis thrombosis, 0.63%/patient-year (Table 3 and 5). All these patients occurred out of hospital with one within 30 days of operation. Four patients were managed successfully with thrombolytic therapy and five patients were managed successfully with reoperation. There was one fatality related to thrombosis diagnosed at autopsy. This patient died one year following fourth cardiac surgical procedure and third mitral valve replacement. The patient was in atrial fibrillation and adequately anticoagulated. There were four cases managed successfully with thrombolytic therapy with one minor thromboembolic event. There were five cases managed successfully with reoperation; all had prosthesis replacement. The one case of thrombosis that occurred early after discharge was managed initially with thrombolytic therapy but developed cardiac tamponade and required reoperation. The thrombosis had resolved at surgery but the prosthesis was replaced. Of the ten combined SJM and CM thrombotic cases, nine had an INR of less than 2.5. One SJM case was adequately anticoagulated at the time of the event. Of the mitral valve replacements who had thromboembolic events with an INR <2.5, 33% were in atrial fibrillation and 67% were in normal sinus rhythm.


   5. Discussion
Top
 Abstract
 1. Introduction
2. Patient population
3. Methods and statistical...
 4. Results
5. Discussion
References
 
The major valve-related complications of mechanical prostheses have been anticoagulant hemorrhage, thromboembolism, including thrombosis, and structural failure. The St. Jude Medical prosthesis was introduced in 1977 and has become the most widely utilized mechanical prosthesis [2–4,9–12,14–20,23]. The bileaflet design of the St. Jude Medical prosthesis has been incorporated into the new generation Baxter–Tekna (formerly Duromedics and Hemex), Sorin Bicarbon (Baxter Mira) and CarboMedics prostheses, as well as the investigational ATS (ATS Medical, Minneapolis, MN) and On-X (Medical Carbon Research Institute, Austin, TX) mechanical prostheses. The St. Jude Medical prosthesis has received documentation of clinical performance to 10 years [9,10,16,19,23]. The purpose of this documentation is to report the experience of the performance of the two predominant bileaflet mechanical prostheses, St. Jude Medical and CarboMedics, in mitral valve replacements. The University of British Columbia commenced utilization of the CarboMedics prosthesis in September 1989 as part of the multicentre investigational study [13,24]. The experience with the CarboMedics and St. Jude Medical prostheses between September 1989 and June 1994 inclusive formulate the patient population of this study. The study is an observational evaluation of the two prostheses.

Mechanical prostheses have been utilized for over 35 years as substitutes for diseased native valves. The successful mechanical prostheses have been the Starr–Edwards caged ball prosthesis and various monoleaflet and bileaflet mechanical prostheses. The question over the past 3 decades has been to provide prostheses with the potential for reduction in thromboembolic phenomena and the related complication of anticoagulant or antithromboembolic hemorrhage. The literature has not provided appropriate evaluation to determine the beneficial effect of advancements in prostheses design [1,7,9,13,16,19,24,26–29]. There have been only two randomized trials, of significance, both comparing the performance of the St. Jude Medical bileaflet prosthesis to the Medtronic–Hall (Medtronic Inc., Minneapolis, MN) monoleaflet prosthesis [2,4]. The current knowledge has been derived primarily from recent reports on the clinical performance of individual prostheses [1–29]. The major concern with these reports has been the wide variation of reported results on thromboembolic events. There remains extensive inconsistency of clarification of definition for most reports do not differentiate between major and minor events and do not indicate the standard of reporting. For mitral valve replacement with mechanical prostheses the incidence of thromboembolic rates have ranged between 0.3 and 6.6%/patient-year [1,8,9–11,13,16,20,22,24]. Smith and coauthors [11] have reported the incidence of thromboembolic events to be 0.3%/patient-year for mitral valve replacement for the St. Jude Medical prosthesis. On the other hand, Horstkotte and colleagues [9] have reported unexpected findings with the St. Jude Medical prosthesis with an incidence of 5.1%/patient-year for mitral replacements. These authors when considering only first or most serious of several events, documented incidence of 4.1%/patient-year, for mitral valve replacement. Ibrahim et al. [16] have also reported high total thromboembolic rates with the St. Jude Medical prosthesis, 4.4%/patient-year for mitral valve replacements. Several reports document only events that occur beyond the early 30 day interval and consequently provide an unfair assessment of patient morbidity and mortality [9,13,14,17,23,24]. Jegaden and investigators [18], on the other hand, have expressed concern over the occurrence of major thromboembolism during the early postoperative period, often when anticoagulation has yet to be adequately controlled. There is also limited information provided on the level of anticoagulation at the time of both thromboembolic and hemorrhagic events. The extent of patient follow-up and depth of evaluation, as well as, the adequacy of anticoagulation management are likely contributing factors to the wide range of reported events.

This report attempts to alleviate some of these concerns by reporting total overall events, events occurring <30 days, events occurring >=30 days and classifying events as major (reversible and permanent), minor, fatal and thrombotic occlusion. The study has documented the adequacy of anticoagulation at the time of event occurrence. An INR level of 2.5 was considered as the minimal level of adequacy of anticoagulant management. The study did not determine the anticoagulant status of patients who did not have a thromboembolic event, or at times remote of an event. The influence of anticoagulant management on hospital and post-hospital, and <=30 days and >30 days thromboembolism has been reported in mitral and multiple valve replacements with the mechanical prostheses populations by Jamieson and collaborators [32].

The overall thromboembolic rate, considering both major and minor events, for mitral replacements was 5.5%/patient-year. These results are comparable to the reported results by Horstkotte et al. [9] and Ibrahim et al. [16] with the St. Jude Medical prosthesis. These results are at variance to the literature for the St. Jude Medical prosthesis, the range from other reports to be 0.6–2.5%/patient-year for mitral replacements [10,11,19,20]. The results with the CarboMedics prosthesis are 0.6–2.27%/patient-year for mitral replacements [8,13,22].

The series documenting comparative studies have also showed varying results [2,4,21]. Aramendi et al. [3] compared thromboembolic rates in the mitral position, 5.23%/patient-year for the St. Jude Medical prosthesis and 5.62%/patient-year for the Björk–Shiley prosthesis. The thromboembolic rates for other monoleaflet prostheses have also been extensively varied [1,2,7,11,29,33]. Fiori et al. [4], reporting on a randomized trial for mitral replacements identified the St. Jude Medical prosthesis rate to be 1.6%/patient-year and the Medtronic-Hall prosthesis rate to be 4.9%/patient-year. Butchart and colleagues [33] reported the mitral Medtronic Hall rate to be 3.0%/patient-year while Kim et al. [21] reported 0.8%/patient-year for mitral Medtronic-Hall implantations. Kim and coauthors [21] also reported on the Björk–Shiley Monostrut prosthesis (Alliance Medical Technology, Irvine, CA), 3.0%/patient-year for mitral replacements. Orszulak and colleagues [6] reported a mitral rate of 4.6%/patient-year with Björk–Shiley standard and convex-concave prostheses. This wide ranging reporting of thromboembolic rates must be related to the detailed nature of evaluation and possibly the extent of anticoagulation.

The most important aspect of thromboembolism is the rates of major events, as well as hemorrhagic events. The major event rate in the present series of combined St. Jude Medical and CarboMedics prostheses is 2.47%/patient-year for mitral replacements. The >=30 day event rates was 2.0%/patient-year. The reports by Horstkotte and Ibrahim and colleagues [9,15] range from 1.2–1.4%/patient-year for mitral replacements. The incidence of anticoagulant hemorrhage in these reports have shown less variation. The major hemorrhagic rate in the authors combined series is 1.5%/patient-year for mitral valve replacements. The hemorrhagic rates for the series of St. Jude Medical prosthesis by Horstkotte and Ibrahim and colleagues [9,15] range from 1.8–2.8%/patient-year for mitral replacements. These apparent differences may explain the higher major event rates in the authors series. The inadequacy of anticoagulation in our series of overall thromboembolic events may also be a contributing factor; 91%, and 75% for mitral replacements <30 days and >=30 days, respectively.

The prostheses thrombosis rates for our combined series was 0.63%/patient-year for mitral replacements. The thrombosis rate reported by Orszulak and coauthors [6] for Björk–Shiley standard and concave-convex prostheses was 0.27%/patient-year. Aagaard et al. [22] and Fiane et al. [27] reported a CarboMedics rate of 0.3%/patient-year. Nitter-Hauge et al. [1] documented the thrombosis rate for the Medtronic-Hall monoleaflet prosthesis at 0.1%/patient-year for mitral implants. The rate of prosthesis thrombosis with the St. Jude Medical and the Björk–Shiley Monostrut has been reported as low [4,10–12,16,18–20] In the authors series of the ten mitral events, five were managed successfully with thrombolysis and five with reoperation. There was a fatality identified at autopsy. Of the total ten thrombosed prostheses, nine had INR levels of less than 2.5 at or immediately prior to the event. There were no independent predictors of prosthesis thrombosis including prosthesis-type, thus documenting no difference in propensity to thrombosis with the CarboMedics and St. Jude Medical prostheses.

The fatality rate from thromboembolism has been infrequently reported. The rate in the authors combined series was 0.13%/patient-year for mitral replacements. The reported fatality rates for mitral prostheses is 0.09–0.5%/patient-year [10–12,16,20].

Sudden unexpected death has been considered to be a valve-related mortality [30,34]. In our series the incidence of sudden unexpected death was 0.06%/patient-year for mitral valve replacement. The incidence of sudden death with the St. Jude Medical prosthesis ranges from 0.06–0.9%/patient-year for mitral replacement except the series reported by Fiori et al. [4], 2.5%/patient-year for mitral valve replacement [10,12,18,20]. Rooney and colleagues [35] studied sudden expected deaths in a large series with the Medtronic-Hall prosthesis. A total of 69 deaths were considered sudden or unwitnessed, 70% were submitted to autopsy and 90% of the deaths were non-prosthetic in origin. In our series unexpected deaths were not considered sudden deaths if there was documented coronary artery disease or known history of angina. Butchart [34] reported in an editorial on the Rooney publication that it was illogical to attribute all sudden deaths to the prosthesis in the absence of an autopsy.

The management and results of dealing with thrombosed mechanical prostheses have received limited attention [35–41]. In our series there were ten thrombosed prostheses and five were subjected to reoperation. Deviri and coauthors [36] reported on mortality of surgical management of obstructed mechanical prostheses, namely Björk–Shiley, Medtronic-Hall and St. Jude Medical. The mortality of prosthesis replacement was 12% and prosthesis declotting, 13%. Martinelli and co-investigators [39], in 1991, evaluated 72 thrombosed obstructions of 3637 patients. The overall mortality was 25% with reoperative mortality of 17%, of 62 patients. Of 57 reoperations, valve re-replacement was performed in 37 and debridement in 27. Re-thrombosis rate was 41% of debrided prostheses. Roudaut et al. [42] reported in 1992 on thrombolytic management of 64 patients with 75 episodes of thrombosis. The success rate was 75% (55), while of 18 failures nine came to emergency surgical management. There were nine overall deaths, four due to cerebrovascular accident, four due to cardiac arrest and one due to hemorrhage. There were 11 cases of embolism, four cerebral resulting in death. The event-free success was 63% with mitral prostheses while 85% with aortic prostheses. In the authors series four cases were treated successfully with thrombolysis for mitral prosthesis thrombosis with one minor thromboembolic event. There always is an embolic risk with thrombolysis. Thrombolysis is likely to be successful if the thrombus is of recent origin and there is no pannus formation. It appears that operation for prosthesis thrombosis should be accompanied with re-replacement and not with thrombus removal.

The appropriate anticoagulant management of mechanical prosthesis is unresolved [43–47]. The goal of therapy is to minimize hemorrhagic complications without an increase of thromboembolic events. The recommended range of anticoagulation for patients with mechanical prostheses-INR 3.0–4.5 has been challenged by several studies [43,44,46,48]. Saour et al. [46] compared low dose versus high dose warfarin anticoagulation and found high level of anticoagulation was associated with increased bleeding but no decrease in the rate of systemic embolism. Altman et al. [44] observed the same results comparing INR 2.0–3.0 with 3.0–4.5 with salicylate acid and dipyridamole. Skudicky et al. [43] found that low dose anticoagulation (INR 2.0–2.5) combined with dipyridamole 300 mg/day systemic embolism and valve obstruction was low and little attention to INR was safe.

Butchart and colleagues [49] made a major contribution by recommending anticoagulation to prosthesis thrombogenicity and patient risk factors. These authors compared low anticoagulation (mean INR 2.5) with moderate anticoagulation (mean INR 3.0) and identified that with in the MVR group with the low group was 80% free of all events and 93% free of serious events at 3 years compared to 89% and 98%, respectively, in the moderate group. This study was conducted with the Medtronic–Hall prosthesis and recommended INR of 3.0 for MVR. Turpie and colleagues [47] studied mechanical prostheses and tissue prostheses plus atrial fibrillation or history of thromboembolism with high 3.0–4.5 INR randomized to salicylatic acid (100 mg/day) with no differentiation to valve position. Major hemorrhagic events in this well controlled randomized study revealed a hemorrhagic rate of 8.5%/patient-year for the aspirin group and 6.6%/patient-year for the placebo group. The authors emphasized major systemic embolism, nonfatal intracranial hemorrhage, death due to hemorrhage or death due to vascular causes with respective rates of 3.9%/patient-year and 9.9%/patient-year but major systemic embolism 1.6%/patient-year and 4.6%/patient-year. The authors concluded that the low increase in bleeding was offset by considerable benefit. One must be critical of this study for unacceptable hemorrhagic rates while identifying some benefit against embolism from Aspirin. As indicated by the authors, a less intense anticoagulation regimen should provide a reduction in major bleeding.

Meschengieser and co-authors [50] reported, in 1997, the results of a randomized trial with mechanical prostheses undifferentiated by position. The patients were randomized to INR 2.5–3.5 plus salicylatic acid 100/mg/day or INR 3.5–4.5. The thromboembolic rate was 1.32%/patient-year for the low-intensity +ASA group compared to 1.48%/patient-year for the high intensity groups. The major hemorrhage rates were 1.13%/patient-year and 2.33%/patient-year, respectively. There was one thrombotic case in the low intensity group but no increase in gastrointestinal hemorrhage. The patient population in this study was primarily Starr–Edwards cage-ball and monoleaflet prostheses.

Butchart et al. [49] acknowledged the influence of atrial fibrillation in mitral disease or alone. Atrial fibrillation without valvular heart disease has a rate in excess of 5%/patient-year and falling to 1.5–3.0%/year with anticoagulation [51–53]. The recommended INR of 3.0 for MVR requires some adjustments for stroke risk factors.

The authors study could not identify any influence of prosthesis type on overall, major or minor thromboembolism and thrombosis. The late major TE rates were high (2.0%/patient-year for mitral replacements) and higher including early events <=30 days. The thrombosis rates were high, as well as in other reported series [11,12,16,18,20]. The commencement of anticoagulation, at our hospitals, on the 3rd to 4th day without heparinization may be less than optimal. The long-term management of anticoagulation by numerous family physicians and internists may require reconsideration and possibly home anticoagulation management [48,54,55]. Irrespective of these concerns, our results parallel the embolic rates confirmed with the well conducted studies of Horstkotte et al. and Ibrahim and colleagues [9,16]. The concluding comment is that mechanical bileaflet prostheses, both CarboMedics and St. Jude Medical, in mitral replacement, carry a high risk of thromboembolic and hemorrhagic complications. The authors recognize the need for a randomized trial with current recommendations for anticoagulation and improved system for adequacy of anticoagulation management. This single institution study could serve for future comparative evaluation of the CarboMedics and St. Jude Medical mechanical prostheses.


   References
Top
 Abstract
 1. Introduction
2. Patient population
3. Methods and statistical...
 4. Results
5. Discussion
References
 

  1. Nitter-Hauge S., Abdelnoor M. Ten-year experience with the Medtronic-Hall valvular prosthesis. A study of 1,104 patients. Circulation 1989;80:143-148.
  2. Antunes M.J. Clinical performance of St. Jude and Medtronic–Hall prostheses:a randomized comparative study. Ann Thorac Surg 1990;50:743-747.[Abstract]
  3. Aramendi J.I., Castellanos E., Serrano A., Madiedo J.B., Ortiz De Salazar A., Agosti J. A comparative study of the St. Jude Medical and Bjork–Shiley convexo-concave prostheses in isolated valve replacement. J Thorac Cardiovasc Surg 1991;32(5):557-563.
  4. Fiore A.C., Naunheim K.S., D'Orazio S., Kaiser G.C., McBride L.R., Pennington D.G., Peigh P.S., Willman V.L., Labovitz A.J., Barner H.B. Mitral valve replacement: randomized trial of St. Jude and Medtronic-Hall prostheses. Ann Thorac Surg 1992;54:68-73.[Abstract]
  5. Subotic S., Petrovic P., Boskovic D., Obrenovic B., Sindjelic R., Lovric Z., Djukic P., Vranes M., Curcic S., Matic A. Clinical and functional evaluation of the CarboMedics prosthetic heart valve in the mitral position. Preliminary results. J Cardiovasc Surg 1990;31(4):509-511.[Medline]
  6. Orszulak T.A., Schaff H.V., De Smet J-M., Danielson G.K., Pluth J.R., Puga F.J. Late results of valve replacement with the Bjork–Shiley valve (1973 to 1982). J Thorac Cardiovasc Surg 1993;105(2):302-311.[Abstract]
  7. Daenen W., Van Kerrebroeck C., Stalpaert G., Mertens B., Lesaffre E. The Bjork–Shiley Monostrut valve. Clinical experience in 647 patients. J Thorac Cardiovasc Surg 1993;106:918-927.[Abstract]
  8. de Luca L., Vitale N., Giannolo B., Cafarella G., Piazza L., Cotrufo M. Mid-term follow-up after heart valve replacement with Carbomedics bileaflet prostheses. J Thorac Cardiovasc Surg 1993;106:1158-1165.[Abstract]
  9. Horstkotte D., Schulte H., Bircks W., Strauer B. Unexpected findings concerning thromboembolic complications and anticoagulation after complete 10 year follow up of patients with St. Jude Medical prostheses. J Heart Valve Dis 1993;2:291-301.[Medline]
  10. Kratz J.M., Crawford F.A., Jr, Sade R.M., Crumbley A.J., Stroud M.R. St. Jude prosthesis for aortic and mitral valve replacement: a ten-year experience. Ann Thorac Surg 1993;56:462-468.[Abstract]
  11. Smith J.A., Westlake G.W., Mullerworth M.H., Skillington P.D., Tatoulis J. Excellent long-term results of cardiac valve replacement with the St. Jude Medical valve prosthesis. Circulation 1993;88(5 Pt 2):II49-II54.
  12. Aoyagi S., Oryoji A., Nishi Y., Tanaka K., Kosuga K., Oishi K. Long-term results of valve replacement with the St. Jude Medical valve. J Thorac Cardiovasc Surg 1994;108:1021-1029.[Abstract/Free Full Text]
  13. Copeland J.G., 3rd, Sethi G.K., Bassett J.S., North Amercian Team of Clinical Investigators. Four year experience with the CarboMedics valve: the North American experience. Ann Thorac Surg 1994;58:630-638.[Abstract]
  14. Fernandez J., Laub G.W., Adkins M.S., Anderson W.A., Chen C., Bailey B.M., Nealon L.M., McGrath L.B. Early and late-phase events after valve replacement with the St. Jude Medical prosthesis in 1200 patients. J Thorac Cardiovasc Surg 1994;107:394-407.[Abstract/Free Full Text]
  15. Horstkotte D., Schulte H.D., Bircks W., Strauer B.E. Lower intensity anticoagulation therapy results in lower complication rates with the St. Jude Medical prosthesis. J Thorac Cardiovasc Surg 1994;107:1136-1145.[Abstract/Free Full Text]
  16. Ibrahim M., O'Kank H., Cleland J., Gladstone D., Sarsam M., Patterson C. The St. Jude Medical prosthesis. A thirteen-year experience. J Thorac Cardiovasc Surg 1994;108:221-230.[Abstract/Free Full Text]
  17. Isomura T., Hisatomi K., Hirano A., Kosuga K., Ohishi K. The St. Jude medical prosthesis in the mitral position. Eur J Cardiothorac Surg 1994;8:11-14.[Abstract]
  18. Jegaden O., Eker A., Delahaye F., Montagna P., Ossette J., Durand de Gevigney G., Mikaeloff P.H. Thromboembolic risk and late survival after mitral valve replacement with the St. Jude Medical valve. Ann Thorac Surg 1994;58:1721-1728.[Abstract]
  19. Khan S., Chaux A., Matloff J., Blanche C., DeRobertis M., Kass R., Tsai T.P., Trento A., Neessim S., Gray R., Czer L. The St. Jude Medical valve: experience with 1000 cases. J Thorac Cardiovasc Surg 1994;108:1010-1020.[Abstract/Free Full Text]
  20. Nakano K., Koyanagi H., Hashimoto A., Kitamura M., Endo M., Nagashima M., Tokunaga H. Twelve years’ experience with the St. Jude Medical valve prosthesis. Ann Thorac Surg 1994;57:697-703.[Abstract]
  21. Kim Y.I., Lesaffre E., Scheys I., Stalpaert G., Flameng W.J., Daenen W.J. The Monostrut versus Medtronic Hall prosthesis:a prospective randomized study. J Heart Valve Dis 1994;3:254-359.[Medline]
  22. Aagaard J., Hansen C.N., Tingleff J., Rygg I. Seven-and-a-half years clinical experience with the CarboMedics prosthetic heart valve. J Heart Valve Dis 1995;4:628-633.[Medline]
  23. Baudet E.M., Puel V., McBride J.T., Grimaud J.P., Roques F., Clerc F., Roques X., Laborde N. Long-term results of valve replacement with the St. Jude Medical prosthesis. J Thorac Cardiovasc Surg 1995;109(5):858-870.[Abstract]
  24. Copeland J.G., 3rd An international experience with the CarboMedics prosthetic heart valve. J Heart Valve Dis 1995;4:56-62.[Medline]
  25. Fiane A.E., Saatvedt K., Svennevig J.L., Geiran O., Nordstrand K., Fr{phi}ysaker T. The CarboMedics valve: midterm follow-up with analysis of risk factors. Ann Thorac Surg 1995;60:1053-1058.[Abstract/Free Full Text]
  26. Bernal J.M., Rabasa J.M., Gutierrez-Garcia F., Morales C., Nistal J.F., Revuelta J.M. The CarboMedics valve:experience with 1049 implants. Ann Thorac Surg 1998;65:137-143.[Abstract/Free Full Text]
  27. Fiane A.E., Geiran O.R., Svennevig J.L. Up to eight years follow-up of 997 patients receiving the CarboMedics prosthetic heart valve. Ann Thorac Surg 1998;66:443-448.[Abstract/Free Full Text]
  28. Abe T., Kamata K., Kuwaki K., Komatsu K., Komatsu S. Ten years’ experience of aortic valve replacement with the Omnicarbon valve prosthesis. Ann Thorac Surg 1996;61:1182-1187.[Abstract/Free Full Text]
  29. Akins C.W. Long-term results with the Medtronic-Hall valvular prosthesis. Ann Thorac Surg 1996;61:806-813.[Abstract/Free Full Text]
  30. Edmunds L.H., Clark R.E., Cohn L.H., Miller D.C., Weisel R.D. Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ann Thorac Surg 1988;46:257–259 and Ann Thorac Surg 1996;62:932-935.
  31. Bodnar E., Butchart E.G., Bamford J., Besselaar A.M.P.H., Grunkemeier G.L., Frater R.W. Proposal for reporting thrombosis, embolism and bleeding after heart valve replacement. J Heart Valve Dis 1994;3:120-123.[Medline]
  32. Jamieson W.R.E., Miyagishima R.T., Tyers G.F.O., Lichtenstein S.V., Munro A.I., Burr L.H. Bileaflet mechanical prostheses in mitral and multiple valve replacement surgery. Influence of anticoagulant management on performance. Circulation 1997;96(Suppl II):II134-II140.
  33. Butchart E.G., Lewis P.A., Grunkemeier G.L., Kulatilake N., Breckenridge I.M. Low risk of thrombosis and serious emboli events despite low-intensity anticoagulation. Experience with 1,004 Medtronic Hall valves. Circulation 1988;78:166-177.
  34. Butchart E.G. The significance of sudden and unwitnessed death after heart valve replacement. J Heart Valve Dis 1994;3:1-4.[Medline]
  35. Rooney S., Moreno de la Santa P., Lewis P.A., Butchart E.G. Sudden death in a large prosthetic valve series based on a single prosthesis:experience with the Medtronic Hall valve. J Heart Valve Dis 1994;3:5-9.[Medline]
  36. Deviri E., Sareli P., Wisenbaugh T., Cronje S.L. Obstruction of mechanical heart valve prostheses: clinical aspects and surgical management. J Am Coll Cardiol 1991;17(3):646-650.[Abstract]
  37. Guerrero Lopez F., Vazquez Mata G., Reina Toral A., Rodriguez Bailon I., Fernandez Mondejar E., Aranegui Lasuen P. Thrombolytic treatment for massive thrombosis of prosthetic cardiac valves. Intensive Care Med 1993;19:145-150.[Medline]
  38. Ledain L.D., Ohayon J.P., Colle J.P., Lorient-Roudaut F.M., Roudaut R.P., Besse P.M. Acute thrombotic obstruction with disc prostheses:Diagnostic considerations and fibrinolytic treatment. J Am Coll Cardiol 1986;7:743-751.[Abstract]
  39. Martinell J., Jimenez A., Rabago G., Artiz V., Fraile J., Farre J. Mechanical cardiac valve thrombosisIs thrombectomy justified?. Circulation 1991;8:III70-III75.
  40. Renzulli A., De Luca L., Caruso A., Verde R., Galzerano D., Cotrufo M. Acute thrombosis of prosthetic valves:A multivariate analysis of the risk factors for a lifethreatening event. Eur J Cardio-Thorac Surg 1992;6:412-421.[Abstract]
  41. Silber H., Khan S.S., Matloff J.M., Chaux A., DeRobertis M., Gray R. The St. Jude valve. Thrombolysis as the first line of therapy for cardiac valve thrombosis. Circulation 1993;87:30-37.[Abstract/Free Full Text]
  42. Roudaut R., Labbe T., Lorient-Roudaut M.F., Gosse P., Baudet E., Fontan F., Besse P., Dallocchio M. Mechanical cardiac valve thrombosis. Is fibrinolysis justified?. Circulation 1992;86:II8-II15.
  43. Skudicky D., Essop M.R., Wisenbaugh T., Skoularigis J., Essop A.R., Dullabh A., Bedhesi S., Strugo V., Sareli P. Frequency of prosthetic valve-related complications with very low level warfarin anticoagulation combined with dipyridamole after valve replacement using St. Jude Medical prostheses. Am J Cardiol 1994;74:1137-1141.[Medline]
  44. Altman R., Rouvier J., Gurfinkel E., D'Ortencio O., Manzanel R., de La Fuente L., Favaloro R.G. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg 1991;101:427-431.[Abstract]
  45. Horstkotte D., Bergemann R., Althaus U., Ebell J.B., Chares M., Dahm M. and Participating Heart Center. German experience with low intensity anticoagulation (GELIA): protocol of a multi-center randomized prospective study with the St. Jude Medical valve. J Heart Valve Dis 1993;2:411-419.[Medline]
  46. Saour J.N., Sieck J.O., Mamo L.A.R., Gallus A.S. Trial of different intensities of anticoagulation in patients with prosthetic heart valves. N Engl J Med 1990;322:428-432.[Abstract]
  47. Turpie A.G., Gent M., Laupacis A., Latour Y., Gunstensen J., Basile F., Klimek M., Hirsh J. Comparison of Aspirin with placebo in patients treated with Warfarin after heart-valve replacement. N Engl J Med 1993;329:524-529.[Abstract/Free Full Text]
  48. Hirsh J., Fuster V. Guide to anticoagulant therapy. Part 2: Oral anticoagulants. Circulation 1994;89(3):1469-1480.[Free Full Text]
  49. Butchart E.G. Prosthesis-specific and patient-specific anticoagulation. In: Butchart E.G., Bodnar E., eds. Current issues in heart valve disease, thrombosis, embolism and bleeding. London: ICR, 1992:293-317.
  50. Meschengieser S.S., Fondevila C.G., Frontroth J., Santarelli M.T., Lazzari M.A. Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves. J Thorac Cardiovasc Surg 1997;113:910-916.[Abstract/Free Full Text]
  51. Halperin J.L., Hart R.G. Atrial fibrillation and stroke:new ideas, persisting dilemmas. Stroke 1988;19:937-941.[Free Full Text]
  52. Lundstrom T., Ryden L. Haemorrhagic and thromboembolic complications in patients with atrial fibrillaton on anticoagulant prophylaxis. J Intern Med 1989;255:137-142.
  53. Anonymous, SPAF Study Group Investigators. Preliminary report of the stroke prevention in atrial fibrillation study. N Engl J Med 1990;322:863–868.[Abstract]
  54. Cortelazzo S., Finazzi G., Viero P., Galli M., Remuzzi A., Parensan L., Barbui T. Thrombotic and hemorrhagic complications in patients with mechanical heart valve prosthesis attending an anticoagulation clinic. Thromb Haemost 1993;69(4):316-320.[Medline]
  55. White R.H., McCurdy S.A., Von Marensdorf H., Woodruff D.E., Jr, Letgoff L. Home prothrombin time monitoring after the initiation of warfarin therapy: a randomized, prospective study. Ann Intern Med 1989;III(9):730-737.



This article has been cited by other articles:


Home page
 J. Thorac. Cardiovasc. Surg.Home page
A. J. Bryan, C. A. Rogers, K. Bayliss, J. Wild, and G. D. Angelini
Prospective randomized comparison of CarboMedics and St. Jude Medical bileaflet mechanical heart valve prostheses: Ten-year follow-up
J. Thorac. Cardiovasc. Surg., March 1, 2007; 133(3): 614 - 622.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
L. S. De Santo, G. Romano, A. D. Corte, F. Tizzano, A. Petraio, C. Amarelli, M. De Feo, G. Dialetto, M. Scardone, and M. Cotrufo
Mitral mechanical replacement in young rheumatic women: Analysis of long-term survival, valve-related complications, and pregnancy outcomes over a 3707-patient-year follow-up
J. Thorac. Cardiovasc. Surg., July 1, 2005; 130(1): 13 - 19.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
G. L. Grunkemeier and Y. Wu
"Our complication rates are lower than theirs": Statistical critique of heart valve comparisons
J. Thorac. Cardiovasc. Surg., February 1, 2003; 125(2): 290 - 300.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
K. H. H. Lim, M. Caputo, R. Ascione, J. Wild, R. West, G. D. Angelini, A. J. Bryan, and S. A. M. Calafiore
Prospective randomized comparison of CarboMedics and St Jude Medical bileaflet mechanical heart valve prostheses: An interim report
J. Thorac. Cardiovasc. Surg., January 1, 2002; 123(1): 21 - 32.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Robert T. Miyagishima
Gary L. Grunkemeier
Guy J. Fradet
Samuel V. Lichtenstein
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jamieson, W.R. E.
Right arrow Articles by Lichtenstein, S. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jamieson, W.R. E.
Right arrow Articles by Lichtenstein, S. V.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS