Asian Cardiovasc Thorac Ann 1998;6:174-178
© 1998 Asia Publishing EXchange Pte Ltd
Effects of Pregnancy on Long-Term Follow-Up of Mitral Valve Bioprostheses
Mustafa Emir, MD,
Gürkan Uzunonat, MD,
Birol Yamak, MD,
A Tulga Ulus, MD,
M Kamil Göl, MD,
Zafer Iscan, MD,
S Fehmi Katircio
lu, MD,
Binali Mavita
, MD,
Ouz Tademir, MD,
Kemal Bayazit, MD
Department of Cardiovascular Surgery Türkiye Yüksek  htisas Hospital Ankara, Turkey
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For reprint information contact: Birol Yamak, MD Department of Cardiovascular Surgery Türkiye Yüksek Ihtisas Hospital Sihhiye, Ankara 06100, Turkey Tel: 90 312 310 3080 Ext. 1247 Fax: 90 312 466 3202 E-mail: ulus{at}escortnet.com
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ABSTRACT
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Between 1986 and 1990, 304 females between 11 and 45 (mean, 33.9 ± 6.9) years of age underwent isolated mitral valve replacement with a bioprosthesis. Thirty-nine of the 285 survivors experienced 48 pregnancies during the late follow-up period (group 1). Structural valve deterioration occurred in 25 (64.1%) of these patients and in 70 (28.4%) of the 246 patients (group 2) who did not become pregnant (p < 0.01). The mean time at which structural valve deterioration occurred was 7.01 ± 1.19 years postoperatively (range, 4.74 to 8.36 years) for group 1 patients and 6.76 ± 1.34 years (range, 2.33 to 10.17 years) for group 2 patients (p > 0.05). Freedom from structural valve deterioration at 10 years was 22.9% ± 8.11% for group 1 and 29.24% ± 6.09% for group 2 (p > 0.05). We concluded that pregnancy did not influence the long-term outcome after mitral valve replacement with a bioprosthesis.
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INTRODUCTION
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Biological cardiac valve substitutes have been used to avoid anticoagulant-related complications in young patients.1–4 Although bioprostheses provide a good quality of life with low rates of thromboembolism, anticoagulant-related bleeding, and valve thrombosis, they have relatively high rates of structural valve deterioration, especially in the younger patient population.5–10 On the other hand, oral anticoagulants must be used after valve replace-ment with a mechanical prosthesis and these drugs are contraindicated during pregnancy because of the risk of hemorrhage and fetal mortality or malformations.11–13
In addition to the cardiovascular effects of pregnancy, it also accelerates the degeneration of bioprostheses. It has been shown that acute structural valve deterioration during pregnancy is an immune process that takes place as a result of increased calcium metabolism. Calcification of a bioprosthesis may be caused by increased plasma immunoglobulins, osteoid plasmocytosis, and histiocytic or other cellular infiltrates.4,12,14 This study was designed to evaluate the long-term effects of pregnancy in respect of structural valve deterioration in women of childbearing age who had undergone isolated mitral valve replacement.
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MATERIALS AND METHODS
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Between 1986 and 1990, 304 females aged between 11 and 45 years underwent isolated mitral valve replace-ment with a Liotta Bioimplant (Bioimplant Canada, Inc., Quebec, Canada) at the cardiovascular surgery clinic of Türkiye Yüksek Ihtisas Hospital. Patients who had valves other than the mitral valve replaced concomitantly or alone were not included in this study. The mean age at operation was 33.9 ± 6.9 years.
Physical examination, telecardiography, electrocardio-graphy, and echocardiography were the preoperative diagnostic tools. Cardiac catheterization was performed on patients over 40 years of age as well as on those suspected of having multiple valve disease, or when the symptoms and echocardiographic findings did not corre-late, or in the presence of serious pulmonary hypertension. The functional status of a patient before and after the operation was classified according to the New York Heart Association (NYHA). The indication for valve replace-ment surgery was in NYHA functional class III or IV.
OPERATIVE TECHNIQUE
All operations were performed with standard techniques of cardiopulmonary bypass using a membrane oxygenator (Terumo-Capiox E; Terumo Corp., Tokyo, Japan). Mode-rate total body hypothermia (28°C to 30°C), cold potas-sium cardioplegia, and topical cooling were used for myocardial protection. All valve replacements were per-formed with simple interrupted sutures. Pledget-supported U-sutures were used when the annulus was heavily calcified. The posterior leaflet was preserved in 11 patients who had only mitral insufficiency with annular dilatation. Additional procedures are summarized in Table 1.
FOLLOW-UP
All patients received 2.5 mg sodium warfarin, 225 mg dipyridamole, and 250 mg aspirin daily during the first 3 postoperative months. After this period, they received only antiplatelet therapy. Postoperative follow-up infor-mation was obtained by examination at 2, 8, and 20 months and yearly thereafter. In some cases, a question-naire was mailed to the patient or follow-up was conducted by telephone interview. Patients were divided into two groups during the follow-up period: group 1 comprised 39 patients who experienced 48 pregnancies; the remaining patients who did not become pregnant were assigned to group 2.
STATISTICAL ANALYSIS
The Kaplan-Meier method was used for calculating actuarial probability of survival and morbidity events. Multivariate (Cox model) proportional hazard regression analysis was used to determine the preoperative risk factors that were significant independent predictors of valve-related complications. A p value of less than 0.05 was considered statistically significant. All results are reported as mean ± standard deviation.
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RESULTS
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The mean age of the 39 patients in group 1 was 30.1 ± 6.6 years. The patients in group 2 had a mean age of 34.6 ± 6.7 years.
HOSPITAL MORTALITY
Death from any cause during operation, or within 30 days if the patient was discharged, or at any time if the patient was not discharged was designated a hospital mortality. Nineteen patients died early after surgery or before discharge. Most of the deaths were attributed to low cardiac output. The overall hospital mortality rate was 6.3%.
FOLLOW-UP
The mean follow-up of hospital survivors was 4.86 ± 0.8 years (range, 1 to 10.45 years) and it was 95.3% com-plete. The total cumulative follow-up period was 2012.1 patient-years. Follow-up was 100% complete for the patients in group 1. The 10-year actuarial survival rate was 93.47% ± 4.56% for group 1 patients and 68.06% ± 6.8 % for group 2 patients (p > 0.05). The overall actuarial survival rate at 10 years was 73.73% ± 5.29% (Figure 1).
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Figure 1. Actuarial survival rates: overall and by group (p > 0.05). Group 1 = patients who experienced pregnancy. Group 2 = patients who did not experience pregnancy.
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Ten incidents of thromboembolic complications were recorded during the follow-up period. The actuarial estimate showed the freedom from thromboembolism to be 94.09% ± 4.07% for group 1 and 95.1% ± 1.91% for group 2 patients at 10 years (p > 0.05). Freedom from thromboembolism for all patients was 94.75% ± 1.74% (Figure 2).
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Figure 2. Freedom from thromboembolism: overall and by group (p > 0.05). Group 1 = patients who experienced pregnancy. Group 2 = patients who did not experience pregnancy.
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During the 10-year follow-up period, 95 of the 285 surviving patients experienced structural valve deteriora-tion. Of the 39 patients who experienced 48 pregnancies during this period (group 1), 25 (64.1%) had structural deterioration. Of the 246 patients (group 2) who did not experience pregnancy, 70 (28.4%) suffered structural valve deterioration (p < 0.01). On the other hand, the mean time at which structural valve deterioration was detected was 7.01 ± 1.19 years (range, 4.74 to 8.36 years) for group 1 compared with 6.76 ± 1.34 years (range, 2.33 to 10.17 years) for group 2 (p > 0.05). Freedom from structural valve deterioration at 10 years was 22.9% ± 8.11% for group 1 and 29.24% ± 6.09% for group 2. The overall probability of living without structural deterioration at 10 years was 26.18% ± 4.18% (Figure 3).
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Figure 3. Freedom from structural valve deterioration: overall and by group (p > 0.05). Group 1 = patients who experienced pregnancy. Group 2 = patients who did not experience pregnancy.
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Twenty patients from group 1 (51.2%) and 63 patients from group 2 (26.14%) underwent reoperation. The freedom from reoperation at 10 years was calculated as 28.10% ± 9.56% for group 1 compared with 23.8% ± 10.6% for group 2 (p > 0.05). Two patients in group 2 who had structural valve deterioration died in the hospital while waiting for reoperation. Ten other patients who were in New York Heart Association functional class II declined reoperation. The overall freedom from reopera-tion at 10 years was 21.51% ± 9.53% (Figure 4).
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Figure 4. Freedom from reoperation: overall and by group (p > 0.05). Group 1 = patients who experienced pregnancy. Group 2 = patients who did not experience pregnancy.
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Twenty-eight (71.7%) of the patients who had a biopros-thetic mitral valve replacement and subsequent preg-nancy, suffered a valve-related complication during the long-term follow-up compared to 88 (36.5%) patients in group 2 (p < 0.01).
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DISCUSSION
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Although replacement of a heart valve is a standard procedure, the ideal valve design remains elusive. All prostheses are associated with a degree of valve-related complications that limits their clinical use. For this reason, clinical success after valve replacement is evaluated by patient survival and freedom from valve-related com-plications such as reoperation, thromboembolism, and hemorrhage related to the use of anticoagulants.15 The choice of prosthesis is generally dependant on the surgeon's preference but the age of the patient is critical to the decision to use a mechanical or a bioprosthetic valve.5 Although mechanical prostheses have a greater long-term durability, this advantage must be weighed against their thrombogenicity and the obligatory use of anticoagulants.5,6,15 Bioprostheses gained early popularity because of their avoidance of thromboembolism and anticoagulant-related hemorrhage. However, structural deterioration is the main reason (90%) for reoperation in patients with bioprosthetic valves in contrast to mechanical valves where thromboembolic complications are the major problem.1,16 Because of their greater durability, mechanical valves are preferred in younger age groups.7,17–20 However, for women of childbearing age who desire pregnancy, bioprosthetic valves are generally recommended because of the teratogenic effects of anticoagulant therapy and the risk of hemorrhage.7
Stroke volume and heart rate increase in pregnancy to peak at the 32nd week with cardiac output increased to 40% above the normal value. Circulating blood volume also increases by 40%, mainly due to increased plasma volume. Because of large arteriovenous fistulas in the placenta, peripheral vascular resistance decreases with a consequent decrease in systemic blood pressure. Although the increased plasma volume causes pulmonary vaso-dilatation, pulmonary artery pressure is stable.21 Concen-trations of circulating coagulation factors increase during pregnancy. The platelet cycle is accelerated causing de-creased fibrinolytic activity and a state of hypercoagula-bility. As a result, there is increased risk of deep venous thrombosis, left atrial thrombosis, mitral stenosis, and thrombus at the site of a prosthetic heart valve. Biological prostheses reduce this risk and are associated with lower fetal and maternal mortality and morbidity.4,11,21–22
Sbarouni and Oakley13 reported no maternal mortality but a 35% incidence of emergency reoperation because of structural valve deterioration among patients with bio-prosthetic valves who experienced pregnancy. Jamieson and colleagues22 reported a 56.1% rate of valve-related complications (mainly structural valve deterioration) in 52 patients who had 94 pregnancies from a series of 237 women under 35 years of age who received bioprosthetic valves. The incidence of structural valve deterioration was 50.9% in women who had a pregnancy compared to 39.6% in women who did not experience pregnancy. In our study, the rate of structural valve deterioration was 64.1% for patients who had a pregnancy compared with a significantly lower rate of 28.4% for those who did not become pregnant. However, the mean interval between surgery and the onset of structural valve deterioration was not significantly different in the two groups and the 10-year freedom from structural valve deterioration was also not significantly different. Pregnancy was also shown to increase the rate of structural valve deterioration of Carpentier-Edwards bioprostheses.7 Badduke and colleagues4 found a much higher rate of valve-related complications among patients who had bioprosthetic valve replacements and became pregnant. They also reported that the period between operation and reoperation in these patients was not statistically different from those who did not experience pregnancy.
The rates of thromboembolic complications associated with bioprostheses are lower than those found with mechanical valves. In our study, only 10 patients had thromboembolic complications and the freedom from thromboembolic complications at 10 years was similar in the two groups. In view of this, we concluded that bioprosthetic valve replacement should be recommended for women of childbearing age who desire pregnancy but it should be regarded as a temporary solution. The increased structural valve deterioration in this age group causes high rates of reoperation and patients who wish to become pregnant should be informed of the benefits and risks associated with bioprosthetic valves.
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Acknowledgments
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Statistical analyses were performed by Kenan Köse at the department of biostatistics, University of Ankara.
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ABSTRACT
INTRODUCTION
