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Ann Thorac Surg 2000;69:457-463
© 2000 The Society of Thoracic Surgeons

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Original Articles

A single-center experience with 1,378 CarboMedics mechanical valve implants

^a Wessex Cardiothoracic Centre, Southampton General Hospital, Southampton, United Kingdom

Address reprint requests to Dr Dalrymple-Hay, Department of Cardiothoracic Surgery, Southampton General Hospital, Tremona Rd, Southampton SO16 6YD, UK
e-mail: mdh{at}btinternet.com

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. The CarboMedics bileaflet prosthetic heart valve was introduced in 1986. We first implanted it in March 1991. The purpose of this study was to analyze our clinical experience with this valve.

Methods. Between March 1991 and December 1997, 1,378 valves were implanted in 1,247 patients, 705 men (56.5%) and 542 (43.5%) women with a mean age of 62 ± 11.9 years (± the standard deviation). Follow-up is 99% complete and totals 3,978 patient-years.

Results. The early mortality rate was 4.4% (55/1,247). The survival rates at 1 year and 5 years were 91.8% ± 0.8% (± the standard error of mean) (n = 1,062) and 79.2% ± 1.4% (n = 281), respectively. Freedom from valve-related complications (linearized rate, 4.9% per patient-year) at 1 year and 5 years was 90.6% ± 0.8% (± the standard error of the mean) (n = 996) and 80.6% ± 1.4% (n = 243), respectively. Linearized rates for various complications were as follows: bleeding events, 1.73% per patient-year; embolic events, 1.76% per patient-year; operated valvular endocarditis, 0.18% per patient-year; valve thrombosis, 0.10% per patient year; and nonstructural dysfunction, 1.21% per patient-year. Freedom from reoperation at 1 year and 5 years was 98.6% ± 0.3% (± the standard error of the mean) (n = 1,070) and 97.7% ± 0.5% (n = 285), respectively.

Conclusions. Midterm results demonstrate that the CarboMedics prosthetic heart valve exhibits a low incidence of valve-related complications.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
The CarboMedics prosthetic heart valve (CarboMedics, Inc, Austin, TX) was introduced into clinical practice in 1986 and became the mechanical implant of choice in our unit in March 1991. It is a second-generation pyrolytic carbon rotatable bileaflet heart valve with several design features that distinguish it from the St. Jude Medical mechanical heart valve. It was approved for clinical use by the Food and Drug Administration in September 1993.

We have implanted mainly the standard aortic and mitral valves. Additional models include the "Top-Hat" supraannular prosthesis, which repositions the valve components from within the annulus to the sinuses of Valsalva. It has been used in patients with small aortic roots as an alternative to root enlargement and in patients having double-valve replacement. The "R" series has also been used as an alternative in patients with a small aortic root. This valve incorporates a reduction in external diameter with no reduction in internal diameter. There is also a composite aortic valve and conduit.

Our experience comprises 1,378 prostheses implanted in 1,247 patients. The series includes 63 "Top-Hat" prostheses, 54 "R" series, and 1,261 standard prostheses. The purpose of this study is to analyze our clinical experience with these valves.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Data collection
All patients aged 18 years or older who underwent mechanical valve replacement with a CarboMedics prosthesis between March 1991 and December 1997 are included. Prior to January 1997, data were collected in a retrospective manner; after this date, all data were collected prospectively.

All patients underwent two-dimensional transthoracic echocardiography prior to hospital discharge. The charts of patients who had implantation between March 1991 and December 1997 were reviewed. At the time of this study, the patients were contacted, and a written questionnaire concerning valve-related complications was sent to them. The general practitioners for the patients were also contacted and questioned concerning valve-related complications. Where necessary for clarity, the local hospitals were also contacted.

Since January 1997, all valve-related complications have been collected prospectively at 6-month intervals by written questionnaires to patients. Confirmation of valve-related complications was collected from the general practitioner and hospital records. For patients who died before January 1997, a review of the general practice, local hospital, and our hospital notes was performed to ensure as complete a collection of valve-related complications as possible. All intraoperative and postoperative hospital events are included in the valve-related complication rates.

Early mortality includes 30-day deaths and hospital deaths that occurred after 30 days but on the same admission as valve implantation. Late death incorporates all patients who have died and were not classified as early deaths. Survival data were obtained by contact with their own doctors, the UK Heart Valve Registry (Hammersmith Hospital, London), and the Office of National Statistics. Cause of death was ascertained from death certificates. Follow-up is 99% complete and totals 3,948 patient-years: aortic valve replacement (AVR), 2,495 patient-years; mitral valve replacement (MVR), 1,096 years; and double-valve replacement (DVR), 357 years. Data were collected until August 8, 1998.

Operative technique
Operations were performed using cardiopulmonary bypass with moderate hypothermia and blood or crystalloid cardioplegia depending on the preference of the surgeon. Suture technique was with simple interrupted 2-0 Ethibond sutures (Ethicon), pledgeted horizontal mattress 2-0 Ethibond sutures, or continuous runs of 2-0 Prolene (Ethicon). The mitral valves were usually implanted in an anti-anatomic position. Where possible, the mitral subvalvular apparatus was preserved.

Anticoagulation
A regimen of warfarin sodium was started for every patient the evening after operation. The international normalized ratio (INR) was checked 3 days postoperatively, and intravenous administration of heparin was begun if the INR was lower than 2. Heparin was discontinued when the INR rose higher than 2. The target range for the INR was 2.5 to 3 for patients with aortic prostheses and 3 to 3.5 for those with mitral prostheses. Patients who underwent coronary artery bypass grafting (CABG) were not given aspirin.

Statistical analysis
All valve-related deaths and complications were defined in compliance with the guidelines established by the Ad Hoc Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity [1]. All continuous variables are expressed as the mean ± the standard deviation. Variables were compared using unpaired t tests, ² tests, and Fisher’s exact tests as appropriate. The relationship between preoperative and operative variables and mortality was explored using logistic regression. Survival curves were obtained using the method described by Kaplan and Meier [2] and include all early deaths. Survival curves were compared using log-rank and generalized Wilcoxon tests. The Cox proportional hazards model [3] was used to relate variables to survival. Probability values of less than 0.05 were considered significant.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Patient data
A total of 1,378 CarboMedics mechanical prostheses were implanted in 1,247 patients, 876 (63.6%) in the aortic position and 502 (36.4%) in the mitral position. There were 705 male (56.5%) and 542 female patients (43.5%) with a mean age of 61.67 ± 11.9 years (± the standard deviation). There were more male patients in the aortic group and more female patients in the mitral group (p < 0.05). The majority of patients were in New York Heart Association functional classes III and IV preoperatively. Of the patients, 219 (17.6%) were having a reoperation, and 773 (62%) underwent operation on an elective basis. Preoperative patient data by type of operation are shown in Table 1.

View larger version (19K): [in this window] [in a new window]   Fig 1. Valve sizes implanted.

Factors significantly associated with an increased risk of operative mortality included the following: sex (female worse) (p = 0.05); higher preoperative New York Heart Association status (p < 0.001); reoperation (p = 0.01); increasing age (p = 0.01); operative category (emergency worst) (p < 0.001); valve replaced (DVR worse than MVR, which was worse than AVR) (p < 0.005); of operation type (DVR + CABG worst) (p < 0.001); performance of CABG (p = 0.04); ischemic time (p < 0.001); and cardiopulmonary bypass time (p < 0.001). However, only operative category (p = 0.03) and cardiopulmonary bypass time (p = 0.01) remained significant on multiple logistic regression.

Three patients required reoperation within 30 days. The first had had a previous MVR with a 2M Starr-Edwards valve in 1967 after a failed closed valvotomy. Endocarditis subsequently developed, and a 23-mm Björk-Shiley valve was implanted in 1981. Before the current operation, he had had increased breathlessness and pleural effusions. At operation, the annulus was enlarged by excising the fibrous ring almost back to ventricular muscle, and a 29-mm CarboMedics valve was implanted. Two hours after he arrived in the intensive care unit, the blood pressure began to fall, and the left atrial pressure rose. A transesophageal echocardiogram showed that one leaflet of the valve was stuck in the closed position. At reoperation, the leaflet had become stuck on a very narrow shelf of tissue on the ventricular side of the valve, the valve was rotated through 90 degrees, and the leaflets moved freely. Another patient required re-replacement of the valve for prosthetic valve endocarditis, the initial indication for operation being endocarditis. One patient who was receiving high doses of steroids for polymyalgia rheumatica had reoperation for a parprosthetic leak.

There was substantial improvement in New York Heart Association functional class at 2 months postoperatively. Of the patients, 74% were in class I and 20%, class II.

Late mortality
The total number of late deaths was 152. Valve-related mortality due to an identifiable cause accounted for 31 (20.4%): bleeding event, 5; intracerebral hemorrhage, 2; thromboembolic stroke, 20; thrombosed valve, 3; and endocarditis, 1. Six were sudden deaths with no postmortem information. Of the remaining 115 late deaths, which were not valve related, 56 were due to cardiac causes and 59, noncardiac causes.

The survival rates (shown ± the standard error of the mean) at 1 year and 5 years were 91.8% ± 0.8% (n = 1,062) and 79.2% ± 1.4% (n = 281), respectively (Fig 2). Patients who underwent AVR exhibited significantly better survival than those who underwent MVR or DVR (log-rank, p = 0.001; generalized Wilcoxon, p = 0.001). There was no difference in survival between patients undergoing operation for aortic stenosis versus aortic regurgitation or between those with mitral stenosis versus mitral regurgitation.

View larger version (13K): [in this window] [in a new window]   Fig 2. Overall survival.

Late morbidity
Valve-related complications
A valve-related complication occurred in 195 patients (linearized rate, 4.9% per patient-year). Freedom from valve-related complications at 1 year and 5 years was 90.6% ± 0.8% (± the standard error of the mean) (n = 996) and 80.6% ± 1.4% (n = 243), respectively (Fig 3). Valve-related complications for each implant position were 103 for AVR (linearized rate, 4.1% per patient-year), 69 for MVR (linearized rate, 6.3% per patient-year), and 23 for DVR (linearized rate, 6.4% per patient-year).

View larger version (11K): [in this window] [in a new window]   Fig 3. Freedom from valve-related complications.

Bleeding events
Sixty-nine patients (linearized rate, 1.73% per patient-year) experienced a major hemorrhage requiring hospitalization, transfusion, or both: 41 with AVR (linearized rate, 1.6% per patient-year); 25 with MVR (linearized rate, 2.3% per patient-year); and 3 with DVR (linearized rate, 0.8% per patient-year). The INR at the time of the event was available for 43 (62%) of these patients, 17 had a prolonged (>4.0) INR.

Thromboembolic episodes
Embolic episodes occurred in 70 patients (linearized rate, 1.76% per patient-year): 41 with AVR (linearized rate, 1.6% per patient-year), 16 with MVR (linearized rate, 1.5% per patient-year), and 13 with DVR (linearized rate, 3.6% per patient-year). The thromboembolic episodes were central in 67 patients (44% permanent) and peripheral in 3.

Four patients had valve thrombosis (linearized rate, 0.10% per patient-year): 1 with AVR (linearized rate, 0.04% per patient-year), 2 with MVR (linearized rate, 0.18% per patient-year), and 1 with DVR (mitral valve) (linearized rate, 0.28% per patient-year). The INR at the time of valve thrombosis in these patients was 1, 2.9, 4.3, and unknown. Two patients were admitted with acute cardiac failure to another hospital and were not referred for surgical intervention. One of the 2 patients who underwent emergency redo valve replacement for valve thrombosis died within 30 days of reoperation; the other is alive.

Operated valvular endocarditis
Seven patients required reoperation for prosthetic valve endocarditis (linearized rate, 0.18% per patient-year): 3 with AVR (linearized rate, 0.12% per patient-year) and 4 with MVR (linearized rate, 0.36% per patient-year). One required reoperation early, within 30 days after implantation (the initial indication for operation was endocarditis), and the remaining 6 underwent reoperation more than 30 days after initial implantation.

Freedom from reoperation
Twenty-three patients required reoperation as a consequence of a morbid event. The most common indications for reoperation were paraprosthetic leak (11 patients) and prosthetic valve endocarditis (7). Two patients required reoperation for valve thrombosis, 2 for pannus ingrowth, and 1 to rotate the valve. Freedom from reoperation at 1 year and 5 years was 98.6% ± 0.3% (± the standard error of the mean) (n = 1,070) and 97.7% ± 0.5% (n = 285) (Fig 4).

View larger version (10K): [in this window] [in a new window]   Fig 4. Freedom from reoperation.

	Comment

Top Abstract Introduction Material and methods Results Comment References

The operative mortality rate in this series (4.4%) compares favorably with that in the majority of other series using alternative mechanical prosthesis: Arom and associates [4], St. Jude Medical, 5.7%; Aoyagi and colleagues [5], St. Jude Medical, 5.0%; Czer and coauthors [6], St. Jude Medical, 8.3%; Keenan and associates [7], Medtronic-Hall, 10.3%; and Akalin and co-workers [8], Omniscience, 8.9%. The operative mortality rate was also lower than that in other CarboMedics mechanical valve series containing more than 500 patients: Copeland [9], Bernal [10], and their co-workers, 7%; Fiane and associates [11, 12], 4.9%; and Rodler and colleagues [13], 9%.

The primary message of this study is to define the incidence of late valve-related complications with the CarboMedics mechanical valve. It is accepted that there may be errors because all the data were not collected prospectively. However, it is considered very unlikely that any valve-related complications of a serious nature would be forgotten by the patient or not recorded in the notes of their doctor, local hospital, or cardiac surgical team.

Unwanted bleeding events (linearized rate, 1.73% per patient-year) occurred with a similar incidence to that in other CarboMedics series [10, 14] and is similar to that reported with other bileaflet valves [15]. There was no significant difference in bleeding rate between AVR, MVR, and DVR. Self-monitoring of levels of anticoagulation by patients at home may lead to a decrease in bleeding events.

Thromboembolic complications (linearized rate, 1.87% per patient-year) had an incidence similar to that in previous CarboMedics series [13, 14]. There were more thromboembolic events in patients having MVR (16 of 371) and DVR (13 of 131) than AVR (41 of 745), but this difference did not reach significance (p = 0.07). Thromboembolic complications also vary according to the level of anticoagulation and the type of prosthesis. No allowance has been made for INR levels, but the incidence does not differ significantly from that in other bileaflet mechanical valve series [15].

The composite thromboembolism and bleeding index has been created to try to show comparisons between prostheses with allowance for variations in INR. A value of 3.29 (AVR, 3.28; MVR, 3.74; DVR, 4.13) for this series is not significantly different from those previously reported [15].

The incidence of nonstructural dysfunction in this series merits further discussion. On initial inspection, the linearized rate of 1.21% per patient-year appears high. However, 45 (93.7%) of these events were paraprosthetic leaks of which only 11 were hemodynamically significant and required reoperation. This reoperation rate is lower than that in other mechanical valve series [16–18]. Of the 11 reoperations: ten involved the mitral position and one, the aortic position. The initial indication for operation was endocarditis in 3 patients. Eight of the mitral valves with paravalvular leaks were inserted with a continuous suture technique. Every patient underwent two-dimensional transthoracic echocardiography prior to discharge, and therefore the 34 patients with trivial regurgitant jets not clinically apparent are included.

Of interest, however, we noticed a larger number of paraprosthetic leaks in valves implanted in the mitral position with a continuous suture technique compared with an interrupted technique. The continuous technique was used by more than one surgeon, and therefore the leaks are not likely to be due to any one individual’s poor performance. The incidence of paraprosthetic leak has decreased since mitral valves have been implanted using an interrupted technique only.

The incidence of operated valvular endocarditis (linearized rate, 0.18% per patient-year) after valve replacement is not significantly different from that in other mechanical valve series [11, 16–19]. The incidence of valve thrombosis is lower than that in the majority of other mechanical valve series [5, 6, 12, 14, 15]. We have not experienced any increase in the incidence of valve thrombosis in mitral implants.

In conclusion, our results demonstrate that the CarboMedics valve can be implanted with an acceptable operative morbidity and mortality and that in the midterm, this valve exhibits a low incidence of valve-related complications.

	References

Top Abstract Introduction Material and methods Results Comment References

 

1. Edmunds L.H., Jr, Clark R.E., Cohn L.H., Grunkemeier G.L., Miller D.C., Weisel R.D. Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ann Thorac Surg 1996;62:932-935.[Abstract/Free Full Text]
2. Kaplan E.L., Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481.
3. Cox D.R., Oakes D. Analysis of survival data. London: Chapman & Hall, 1984.
4. Arom K.V., Nicoloff D.M., Kersten T.E., Northrup W.F., III, Lindsay W.G., Emery R.W. Ten years’ experience with the St. Jude Medical valve prosthesis. Ann Thorac Surg 1989;47:831-837.[Abstract]
5. 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]
6. Czer L.S., Chaux A., Matloff J.M., et al. Ten-year experience with the St. Jude Medical valve for primary valve replacement. J Thorac Cardiovasc Surg 1990;100:44-55.[Abstract]
7. Keenan R.J., Armitage J.M., Trento A., et al. Clinical experience with the Medtronic-Hall valve prosthesis. Ann Thorac Surg 1990;50:748-753.[Abstract]
8. Akalin H., Corapcioglu E.T., Ozyurda U., et al. Clinical evaluation of the Omniscience cardiac valve prosthesis. Follow-up of up to 6 years. J Thorac Cardiovasc Surg 1992;103:259-266.[Abstract]
9. Copeland J.G., III, Sethi G.K., North American team of clinical investigators for the CarboMedics prosthetic heart valve. Four-year experience with the CarboMedics valve. Ann Thorac Surg 1994;58:630-638.[Abstract]
10. Bernal J.M., Rabasa J.M., Gutierrez-Garcia F., Morales C., Nistal J.F., Revuelta J.M. The CarboMedics valve. Ann Thorac Surg 1998;65:137-143.[Abstract/Free Full Text]
11. 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]
12. Fiane A.E., Saatvedt K., Svennevig J.L., Geiran O., Nordstrand K., Frøysaker T. The CarboMedics valve. Ann Thorac Surg 1995;60:1053-1058.[Abstract/Free Full Text]
13. Rödler S.M., Moritz A., Schreiner W., End A., Dubsky P., Wolner E. Five-year follow-up after heart valve replacement with the CarboMedics bileaflet prosthesis. Ann Thorac Surg 1997;63:1018-1025.[Abstract/Free Full Text]
14. Copeland J.G., III The CarboMedics prosthetic heart valve. Semin Thorac Cardiovasc Surg 1996;8:237-241.[Medline]
15. Akins C.W. Results with mechanical cardiac valvular prostheses. Ann Thorac Surg 1995;60:1836-1844.[Abstract/Free Full Text]
16. Vallejo J.L., Gonzalez-Santos J.M., Albertos J., et al. Eight years’ experience with the Medtronic-Hall valve prosthesis. Ann Thorac Surg 1990;150:429-436.
17. Fernandez J., Laub G.W., Adkins M.S. 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]
18. Copeland J.G., III An international experience with the CarboMedics prosthetic heart valve. J Heart Valve Dis 1995;4:56-62.[Medline]
19. Khan S., Chaux A., Matloff J., et al. The St. Jude Medical valve. Experience with 1,000 cases. J Thorac Cardiovasc Surgery 1994;108:1010-1020.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Robert K. Lamb James L. Monro Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dalrymple-Hay, M. J.R. Articles by Monro, J. L. Search for Related Content PubMed PubMed Citation Articles by Dalrymple-Hay, M. J.R. Articles by Monro, J. L.