|Year : 2017 | Volume
| Issue : 1 | Page : 17-23
Midterm outcomes of mechanical versus bioprosthetic valve replacement in middle-aged patients: An Indian scenario
Dheeraj Sharma1, Anula Sisodia2, Sanjeev Devgarha2, Rajendra Mohan Mathur2
1 Department of Paediatric Cardiac Surgery, Superspeciality Paediatric Hospital and Postgraduate Teaching Institute Noida, Uttar Pradesh, India
2 Department of Cardiothoracic and Vascular Surgery, SMS Medical College, Jaipur, Rajasthan, India
|Date of Web Publication||8-Mar-2017|
Dr. Dheeraj Sharma
House No. 530, Raja Park, Jaipur - 302 004, Rajasthan
Source of Support: None, Conflict of Interest: None
Objective: The goal of this study is to evaluate and compare the midterm outcomes of bioprosthetic heart valve replacement in terms of survival, valve-related events, quality of life, and economic aspects of treatment in population age 45 years and above in females and 48 years in males and their comparison with mechanical valve recipients.
Materials and Methods: The patient population under age group of 45–60 years is randomly divided into two groups: One receiving bioprosthetic valves and other receiving mechanical valves. Patients were followed up and data are analyzed.
Results: The overall 10-year survival was similar in patients receiving bioprosthetic heart valve and mechanical heart valves. The incidence of major bleeding episodes was very high with mechanical valves (mitral valve replacement [MVR] = 14.3% and aortic valve replacement [AVR] =7.2%) as compared to 0.6% and 0.8% with bioprosthetic MVR and AVR, respectively. About 1.02% of patients with tissue valves have episodes of thromboembolism versus 8.3% patients with mechanical valves. Acute valve thrombosis rates were high in mechanical valve (3.1% vs. 0.0%). Incidences of endocarditis were also more with mechanical valve replacement group (2.3% vs. 0.3%). The quality of life was also better in patients with bioprosthetic valves.
Conclusions: Bioprosthetic heart valves seem to be more beneficial in the Indian scenario as compared to mechanical valves because of low incidence of mortality and valve-related events and better quality of life.
Keywords: Bioprosthesis, bleeding, comparison, endocarditis, heart valves, mechanical, thromboembolism
|How to cite this article:|
Sharma D, Sisodia A, Devgarha S, Mathur RM. Midterm outcomes of mechanical versus bioprosthetic valve replacement in middle-aged patients: An Indian scenario. Heart India 2017;5:17-23
|How to cite this URL:|
Sharma D, Sisodia A, Devgarha S, Mathur RM. Midterm outcomes of mechanical versus bioprosthetic valve replacement in middle-aged patients: An Indian scenario. Heart India [serial online] 2017 [cited 2018 Jun 22];5:17-23. Available from: http://www.heartindia.net/text.asp?2017/5/1/17/201745
| Introduction|| |
Although many advances have been made in the design and construction of prosthetic heart valves since the first successful human valve replacement performed by Starr and Edwards and Harken et al. in 1960, none of the currently available prosthetic heart valves approach the normal heart valve in either hemodynamic function or freedom from valve-related complications. The mechanical valves offer satisfactory hemodynamic function and have advantage of long-term durability but are thrombogenic, and patients require lifelong rigid protocol of anticoagulation with them and are associated with their side effects. Bioprosthetic heart valves are less thrombogenic and do not require anticoagulation for long term; however, they have problems with durability. In elderly and young patients, we have some relatively clear guidelines for type of valve to be preferred, but guidelines remained to be defined for middle-aged patients in age group of 45–60 years, especially in the Indian scenario where the target population differs markedly from Western countries in terms of life expectancy, economical factors, general make of body, access to medical facilities and literacy, and awareness about the health problems. This study is a prospective and retrospective study to evaluate the midterm outcomes of currently available bioprosthetic and mechanical heart valves in patients of age group of 45–60 years.
| Materials and Methods|| |
A total of 3254 patients were studied extended over a period of 15 years, and out of these, 295 patients received bioprosthetic heart valves out of which 2995 who received mechanical valves and 259 who received bioprosthetic valves were in age group of 45–60 years who had first time aortic valve replacement (AVR), mitral valve replacement (MVR), or double valve replacement (DVR) who received prostheses that are still commercially available today. This study spans from January 1999 to December 2014. To start the study, formal clearance from Ethical Committee was taken.
Follow-up information was obtained by personal interviews and was completed by telephone interviews. The questionnaire consisted of the Nottingham health profile (NHP), assessing quality of life, and general questions concerning postoperative complications, further stay in hospital care, New York Heart Association (NYHA) status, dietary habits, etc. Answers indicating serious events such as bleeding, reoperation, and endocarditis were verified by telephone contact. The NHP contains 38 subjective statements divided into six sections as follows: energy, pain, emotional reaction, sleep, social isolation, and physical mobility. The number of statements in each section varies from three in the energy section to nine in the emotional reaction section. Scale scores range from 0 to 100, with a lower score indicating a better-perceived quality of life.
Data were analyzed with the software package SPSS (SPSS Inc., Chicago, Illinois, USA). All continuous data were expressed as mean (standard error of the mean) and compared by the Mann–Whitney test. Dichotomic variables were evaluated by the univariable Chi-square test and Fisher's exact test.
As the scores for each section of the NHP were not normally distributed, we converted the scores into a binary variable. A score below the 75% quartile was coded as 0, and a score above or equal to this value was coded as 1, which corresponds to an impaired quality of life in the respective NHP section. Deterioration of the NYHA class after the operation was also coded as a binary variable: 0 was assigned to patients who were in the same or a lower NYHA class and 1 was assigned to patients who were in a higher NYHA class.
Choice of prosthesis
The selection of a mechanical or bioprosthetic valve was made following a detailed preoperative discussion between the surgeon, patient, and family members (when applicable). The pros and cons of mechanical or bioprosthetic valves were described, including the need for anticoagulation after mechanical valve implantation or the possible need for reoperation after tissue valve implantation. The decision of mechanical or bioprosthesis selection was left entirely to the individual patient and his/her caregivers. After properly explaining the pros and cons of every type of valve and associated complications and risks of surgery, informed consent was taken from patient itself and their attendants.
The prosthesis model implanted was at the discretion of the operating surgeon.
Patients with mechanical prostheses or chronic atrial fibrillation (AF) were anticoagulated with warfarin according to guidelines in effect at the time as previously described. Briefly, these consisted of a target prothrombin time or international normalized ratio of 2.0–3.0 after mechanical AVR and 2.5–3.5 after mechanical MVR. The addition of aspirin (81 mg daily) to warfarin/coumarin was left to the discretion of the surgeon. In patients who underwent bioprosthetic valve implantation, warfarin/coumarin anticoagulation was used for 4 months after operation. Anticoagulants were subsequently discontinued if sinus rhythm was maintained, and no other indication of anticoagulation was present. Nonanticoagulated patients were kept on aspirin only. Patients who developed anticoagulation in postoperative period were anticoagulated according to AF protocol.
Midterm outcomes after valve replacement surgery, including survival and freedom from reoperation, were compared between patients with mechanical and bioprosthetic valves. Prosthesis-related complications were recorded according to the guidelines for reporting morbidity and mortality after cardiac valvular operations. Briefly, stroke was defined as the presence of a neurological deficit lasting more than 3 weeks and was confirmed with computerized tomography of the head., Bleeding events were classified, as major, if they required surgery, hospital admission, blood transfusion, were intracranial in location or caused death. Reoperation was defined as any operation that repaired, altered, or replaced a previously operated valve., [Table 1] shows the number of patients with different valve replacements, and [Table 2] shows the operative and preoperative characteristics of patient population of different type of valves.
| Results|| |
Early postoperative mortality
Early postoperative mortality was 4.3% and 5.9% after mechanical AVR and MVR, respectively. On the other hand, the early mortality following bioprosthetic MVR and AVR was 6.6% and 4.7%, respectively. Double valve recipients have early mortality similar to MVR in respective category [Figure 1].
Preoperative risk factors for operative mortality were pulmonary artery hypertension, advanced NYHA class, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), deranged liver function test, hypertension, and obesity.
There was no difference in operative mortality between the recipients of mechanical and of biological prostheses (P = 0.929).
Stay in Intensive Care Unit
Mean stay in intensive care (including intermediate care) was 6 days; 23% of patients stayed in the Intensive Care Unit longer than 5 days. Risk factors for a prolonged stay in intensive care were age more than 70 years, history of renal disease, hypertension, and advanced NYHA class.
There was no overall difference between the bioprosthesis and mechanical prosthesis groups (P = 0.35) but patients who were in NYHA Class IV before the operation had an increased risk of a prolonged stay.
Duration of mechanical ventilation
The mean duration of ventilation was 14 h. 14% of patients had prolonged ventilation (>1 day). Predictors for prolonged ventilation were age above 70 years, COPD, CHF, pulmonary artery hypertension, and emergency procedure.
For all patients receiving mechanical valves, no significant difference in the risk of prolonged ventilation was found (P = 0.38).
There was no significant difference in midterm survival after AVR and MVR, after 10 years between the two valve type groups (P = 0.25 and 0.97, respectively). However, survival in the first 5 years is more with bioprosthetic heart valves as they are not associated with high incidences of severe bleeding and stroke and fatal complications such as valve thrombosis which are more associated with mechanical valves because of strict anticoagulation protocol. Diabetes mellitus, advanced NYHA class, history of renal disease, AF, higher age, and male sex were significantly associated with survival duration. The overall 5-, 10-year survival was 76.0% ± 2.1%, 53.2% ± 4.2% after mechanical AVR; 83.6% ± 5.7%, 61.1% ± 12.6% after tissue AVR; 72.0% ± 3.2%, 52.1% ± 4.6%, after mechanical MVR; and 84.1% ± 4.1%, 67.9% ± 7.4% after tissue MVR, respectively. The overall 5- and 10-year survival after DVR was 76.9% ± 6.3% and 54.1% ± 10.1%, respectively [Figure 2].
The incidence of thromboembolic episodes is much higher in patients receiving mechanical heart valves (MVR = 8.3% and AVR = 5.1%) as compared to bioprosthetic group (MVR = 1.02% and AVR = 0.9%). On multivariate testing, there was a tendency toward more thromboembolic events among patients with a history of smoking [Figure 3].
Following MVR, independent risk factors for a thromboembolic event included the presence of a mechanical valve (P = 0.0009) and female gender (P = 0.03). Preoperative left atrial diameter, preoperative NYHA class, left ventricular grade, and year of surgery had no significant effect on thromboembolism after AVR or MVR.
For incidence of thromboembolism at mitral position, there is significant difference between mechanical and bioprosthetic heart valves (P = 0.0009).
Severe bleeding episodes
The incident of major bleeding episode is also significantly higher in mechanical valve group (MVR = 14.3% and AVR = 7.2%) as compared to bioprosthetic valve group (MVR = 0.6% and AVR = 0.8%). The presence of mechanical valve is associated with increased incidence of bleeding (P < 0.0001). In addition, the presence of mechanical valve is associated with more incidences of bleeding than bioprosthetic ones, but the incidence is not statically significant (P = 0.16). Bleeding is seen in about 10.1% cases of mechanical valve DVR as compared to 1.1% cases of bioprosthetic group [Figure 4].
Acute valve thrombosis is a life-threatening complication and is more associated with mechanical valves as the bioprosthetic heart valves tend to degenerate over time gradually. The incidence among mechanical valve group is 3.1% for MVR and 1.2% for AVR. There is no incidence of valve thrombosis in bioprosthetic group. The presence of mechanical heart valve is clearly a risk factor of valve thrombosis and is associated with increased mortality (P = 0.0175). Incidences of valve thrombosis for DVR are similar to MVR group, and in most of the situations, only mitral valve was involved.
The incidence of endocarditis following mechanical valve replacement (MVR = 2.3% and AVR = 1.1%) is also higher than the bioprosthetic group (MVR = 0.3% and AVR = 0.2%). The association of endocarditis with mechanical valve is higher for mitral position than aortic position, but the association is not statistically significant (P > 0.05 for both positions). The incidence of endocarditis was nearly similar to MVR group for DVR.
The incidence for reoperation later in life is nearly similar in both groups, and there was no significant difference among two groups at any position (P = 0.45 for mitral and P = 0.75 for aortic position). Reoperation rates were 0.9% for mechanical MVR and 1.2% for bioprosthetic MVR. For AVR, rates were 1.03% for mechanical and 1.23% for bioprosthetic group. For DVR, the reoperation rates were 2.1% for mechanical and 2.45% for bioprosthetic group.
Quality of life
The results of the NHP questionnaire were compared with results of the general population. The incidence of a score higher than the 75th quartile was 23% per patient year for energy, 18% for pain and emotional reaction, 29% for sleep, 26% for social isolation, and 30% for physical mobility.
Patients requiring anticoagulation had nearly a twofold increased risk for an impaired emotional reaction. Although no significant statistical differences were found between recipients of biological and of mechanical valves and between patients requiring anticoagulation and patients not requiring anticoagulation in all sections up to 30% of mechanical valve recipients would like to change their decision in favor of bioprosthetic heart valves. The most commonly cited reason for the preference of bioprosthetic heart valves is compulsion of changing the dietary habits and lifestyle, especially in young patients, patients involved in various sports, patients who require frequent air travels and those living in rural remote areas. Life restrictions due to rigid anticoagulation protocol are also a major cause of dislike toward mechanical heart valves.
Energy (P = 0.56, P = 0.82), pain (P = 0.26, P = 0.36), sleep (P = 0.59, P = 0.24), social isolation (P = 0.70, P = 0.81), and physical mobility (P = 0.68, P = 0.32, respectively).
Patients with mechanical heart valves need to take anticoagulants lifelong to keep the valves functional. These drugs are expensive and are not routinely available in remote rural areas as well as patient had to visit their doctor for routine monitoring of the coagulation profile, all these factors impose great economical stress on patient and in time of crisis may lead to discontinuation of drugs which may lead to lethal complications. The problem may aggravate several times in case of female patients due to various socioeconomical hurdles and poor literacy rates which was even more aggravated during menstruation and pregnancy. On the other hand, bioprosthetic heart valves do not need anticoagulation for lifelong thus are free from economic and socioeconomic drawbacks associated with mechanical valves.
| Discussion|| |
Valve replacement in the middle-aged adult leads to a difficult choice between the lifelong anticoagulation of a mechanical prosthesis versus a bioprosthesis with limited long-term durability necessitating eventual reoperation. In this follow-up, study of 3254 patients between 45 and 60 years of age who underwent AVR and/or MVR with modern prostheses, multivariate analyses indicated that: (1) Long-term survival is equivalent between patients who underwent AVR and those who underwent MVR, with no significant survival difference between patients implanted with a mechanical versus a bioprosthetic valve in any of the implant positions; (2) the incidence of acute valve failure due to valve thrombosis is a life-threatening complication and is more associated with mechanical valve at mitral position, especially in early postoperative period; (3) the incidence of thromboembolic events and bleeding events is greater in patients with mechanical valves, especially those with MVR; (4) the incidence of reoperation is relatively similar in both the types of heart valves; and (5) incidences of endocarditis are also more common with mechanical valve group, especially at mitral position.
The ultimate aim of heart valve surgery is to extend life expectancy and improve quality of life. This study demonstrated that among middle-aged patients, survival does not appear to be affected by the type of prosthesis. These results confirm those reported by others who have also found that the choice of prosthesis does not have a significant effect on midterm survival after valve replacement in patients younger than 65 years of age., However, our study shows that in the Indian scenario survival in the first 5 years is more with bioprosthetic heart valves as they are not associated with high incidences of severe bleeding and stroke and fatal complications such as valve thrombosis which are more associated with mechanical valves because of strict anticoagulation protocol, this is also due to fact that population living in remote rural areas do not have access to medical facilities and they are always at risk of treatment discontinuation and are frequently lost to follow-up. Regarding quality of life, Perchinsky et al. studied the quality of life of 200 patients aged 51–65 years who had undergone either mechanical or tissue AVR 2–12 years earlier. Mechanical valve patients were more bothered by valve sounds, were more concerned about the frequency of medical visits and blood tests, and were more worried about the possibility of anticoagulant-related bleeding events. Bioprosthetic valve patients, on the other hand, were more fearful of the need for reoperation. According to Perchinsky et al., 97% of patients reported that they would make the same decision again with regard to valve replacement, with no significant difference between the two groups. However, the present study seems to contradict the results of the previous studies as about 30% patients with mechanical heart valves want to change their decision.
In patients older than 65 years of age, evidence supports the use of bioprostheses because of low rates of structural valve deterioration and a low incidence of thromboembolic and hemorrhagic complications.,,,,, However, in younger patients, tissue valves develop early calcification due to an increased turnover of calcium, fatigue-induced lesions, and collagen degeneration., While more promising results of newer generation, bioprostheses have been reported in younger populations, younger age remains a risk factor for reoperation after implantation of a bioprosthesis. Carrier et al. reported an impressive 10-year freedom from valve replacement of 93% ± 3% for patients 55–65 years old with Carpentier–Edwards pericardial valves in the aortic position. These figures are more or less similar for bioprosthetic AVR patients observed in this cohort.
Although mechanical prostheses are used frequently for valve replacement in middle-aged patients, they have important drawbacks, including the need for lifelong anticoagulation.
The results of this cohort study confirm the results presented by other groups demonstrating a higher incidence of thromboembolic , and bleeding , complications with mechanical valves compared to bioprostheses. Major bleeding occurred more often following mechanical MVR among the middle-aged patients in this study, likely related to the more aggressive anticoagulation and higher incidence of AF in MVR patients. Fortunately, thromboembolic and hemorrhagic complications occur less frequently and result in less death in patients less than 65 years of age compared to older patients., Nonetheless, the need for long-term anticoagulation and the associated restrictions on an active lifestyle are a burden that should not be underestimated.
Coming to the scenario in India and Southeast Asia where the life expectancy is in the mid-60s and illiteracy with poverty is prevalent and patient population has poor compliance, as well as health care is not available in remote areas, our study shows that these patients might be better suited for bioprosthetic valves as they are less demanding to patient and less monitoring and follow-up are required and are better tolerated economically in the postoperative period. According to our study, the bioprosthetic valves are better suited to the Indian population also the fact that life expectancy of patients with valvular heart disease requiring surgery is 10–20 years on an average depending on preoperative NYHA class and the presence of rheumatic activity (in the Indian scenario) and most of cardiac deaths related to valvular events is due to severe bleeding and thromboembolic events it would be better to provide these patients with bioprosthetic heart valves which usually lasts 10–15 years and also have very less incidence of valve-related events. The patient with bioprosthetic valves can be examined and evaluated at 1, 5, 7, 10, 12, and 15 years and in case reoperation is required for valve-related event, patient can be taken for surgery. As it is well established that mortality of redo surgery is more or less similar to first operation, and the additional cost of second operation is largely similar to the expenditures on anticoagulation, cost of repeated monitoring of coagulation profile, and cost associated with regular visits to clinicians in patients with mechanical valves. Hence, our study which is largest study of its type favors liberalizing the age for implantation of bioprosthetic heart valves from 65 to 50 years, especially in the Indian scenario.
| Conclusions|| |
Although valve replacement in a middle-aged patient is a common clinical scenario, very little published data exists supporting the use of one valve type or the other in this particular age group. The findings of this study may allow patients and clinicians to better understand and quantify long-term survival and the risk of major events after valve replacement in middle-aged adults.
As the largest series of middle-aged patients to date, this study suggests that mechanical valves may have a higher rate of major complications compared to tissue valves during midterm follow-up, this is specially in context of Indian and subcontinental countries where the health facilities are not easily amenable in remote areas, illiteracy rate, and poverty is high, health is on low priority, and compliance of patient is extremely poor and the life expectancy is somewhere around early 60s.
While definitive conclusions await the accumulation of additional follow-up and further study, at this time, the data do support lowering the usual cutoff for implantation of a tissue valve below the age of 65 to at least 50 years as the life expectancy in Indian and Southeast Asian countries is in early 60s which does not reach the Western cutoff of 65 years for implantation of bioprosthetic heart valves.
Nonetheless, we believe that decisions regarding the choice of prosthesis need to be individualized and discussed between the patient and the treatment team. Factors that must be taken into account include the presence of comorbidities affecting long-term survival, the risks and inconvenience of anticoagulation, the risks associated with reoperation, lifestyle issues, and patient personal preferences and also the demographic and socioeconomic profile of target population.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kohlmann T, Bullinger M, Kirchberger-Blumstein I. German version of the Nottingham Health Profile (NHP): Translation and psychometric validation. Soz Praventivmed 1997;42:175-85.
Ruel M, Masters RG, Rubens FD, Bédard PJ, Pipe AL, Goldstein WG, et al.
Late incidence and determinants of stroke after aortic and mitral valve replacement. Ann Thorac Surg 2004;78:77-83.
Edmunds LH Jr., Clark RE, Cohn LH, Grunkemeier GL, Miller DC, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ad Hoc Liaison Committee for standardizing definitions of prosthetic heart valve morbidity of the American Association for Thoracic Surgery and the Society of Thoracic Surgeons. J Thorac Cardiovasc Surg 1996;112:708-11.
Ruel M, Kulik A, Rubens FD, Bédard P, Masters RG, Pipe AL, et al.
Late incidence and determinants of reoperation in patients with prosthetic heart valves. Eur J Cardiothorac Surg 2004;25:364-70.
Jamieson WR, von Lipinski O, Miyagishima RT, Burr LH, Janusz MT, Ling H, et a
l. Performance of bioprostheses and mechanical prostheses assessed by composites of valve-related complications to 15 years after mitral valve replacement. J Thorac Cardiovasc Surg 2005;129:1301-8.
Carrier M, Pellerin M, Perrault LP, Pagé P, Hébert Y, Cartier R, et al.
Aortic valve replacement with mechanical and biologic prosthesis in middle-aged patients. Ann Thorac Surg 2001;71 5 Suppl: S253-6.
Khan SS, Trento A, DeRobertis M, Kass RM, Sandhu M, Czer LS, et al.
Twenty-year comparison of tissue and mechanical valve replacement. J Thorac Cardiovasc Surg 2001;122:257-69.
Perchinsky M, Henderson C, Jamieson WR, Anderson WN Jr., Lamy A, Lowe N, et al.
Quality of life in patients with bioprostheses and mechanical prostheses. Evaluation of cohorts of patients aged 51 to 65 years at implantation. Circulation 1998;98 19 Suppl: II81-6.
Frater RW, Furlong P, Cosgrove DM, Okies JE, Colburn LQ, Katz AS, et al.
Long-term durability and patient functional status of the Carpentier-Edwards Perimount pericardial bioprosthesis in the aortic position. J Heart Valve Dis 1998;7:48-53.
Cosgrove DM, Lytle BW, Taylor PC, Camacho MT, Stewart RW, McCarthy PM, et al.
The Carpentier-Edwards pericardial aortic valve. Ten-year results. J Thorac Cardiovasc Surg 1995;110:651-62.
Rizzoli G, Bottio T, Thiene G, Toscano G, Casarotto D. Long-term durability of the Hancock II porcine bioprosthesis. J Thorac Cardiovasc Surg 2003;126:66-74.
Masters RG, Haddad M, Pipe AL, Veinot JP, Mesana T. Clinical outcomes with the Hancock II bioprosthetic valve. Ann Thorac Surg 2004;78:832-6.
O'Brien MF, Harrocks S, Stafford EG, Gardner MA, Pohlner PG, Tesar PJ, et al.
The homograft aortic valve: A 29-year, 99.3% follow up of 1,022 valve replacements. J Heart Valve Dis 2001;10:334-44.
Langley SM, McGuirk SP, Chaudhry MA, Livesey SA, Ross JK, Monro JL. Twenty-year follow-up of aortic valve replacement with antibiotic sterilized homografts in 200 patients. Semin Thorac Cardiovasc Surg 1999;11 4 Suppl 1:28-34.
Berrebi AJ, Carpentier SM, Phan KP, Nguyen VP, Chauvaud SM, Carpentier A. Results of up to 9 years of high-temperature-fixed valvular bioprostheses in a young population. Ann Thorac Surg 2001;71 5 Suppl: S353-5.
Gross C, Klima U, Mair R, Brucke P. Aortic homografts versus mechanical valves in aortic valve replacement in young patients: A retrospective study. Ann Thorac Surg 1998;66 6 Suppl: S194-7.
Carpentier SM, Carpentier AF, Chen L, Shen M, Quintero LJ, Witzel TH. Calcium mitigation in bioprosthetic tissues by iron pretreatment: The challenge of iron leaching. Ann Thorac Surg 1995;60 2 Suppl: S332-8.
Jamieson WR, Miyagishima RT, Grunkemeier GL, Germann E, Henderson C, Lichtenstein SV, et al
. Bileaflet mechanical prostheses for aortic valve replacement in patients younger than 65 years and 65 years of age or older: Major thromboembolic and hemorrhagic complications. Can J Surg 1999;42:27-36.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]