Prospective Observational Study

Management Issue in Pregnant Patients with Mechanical Prosthetic Valves in Rural and Semi-urban North Indian Population at a Tertiary Care Institution.
Varuna Varma*, MCh., Nirmal Gupta*, MCh., Amrit Gupta MS**. *Department of CVTS, **Department of Maternal and Reproductive Health, SGPGIMS, Raibareli Road, Lucknow, India. 226014. Corresponding author: Prof Nirmal Gupta Head of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Email: nirmal.gupta@sgpgi.edu.in Abstract: Objectives: To evaluate the most effective, practical and uniform Anticoagulation Regimen suited to rural and semi-urban Indian pregnant women with mechanical heart valves with low socio-economic status and to observe its impact on the pregnancy outcomes. Material Methods: Between April 2002- till May 2013, 683 married young women aged between 19-35 years (child bearing age) received mechanical prosthetic valves at a single unit.All women received only oral Nicoumalone as anticoagulant as standard drug of care under supervision of an obstetrician trained to manage high-risk pregnancies at a medical university hospital at our MRH unit. Results: 27 women died within 30 days following operation due to cardiac causes. In the remaining six hundred and fifty-six (656) women another 69 died or were lost to follow-up. The median follow-up of 587 survivors (who are in regular follow-up) was 6.5 years. 69women out of 587 became pregnant during this period on 1 or multiple occasions. 43 women had successful deliveries and rest 26 had single or multiple stillbirths. Incidence of stillbirth in those who delivered successfully was lower. Fetal mortality was 37.68% and none of the pregnant women had valve thrombosis .All 33women showed successful outcome except 6 children out of 43who developed anticoagulation related embryopathy. Conclusion: Our Experience showed that Heparin is neither effective nor safe for long-term use in pregnancy. The fetal outcome was slightly better in women taking the combination of heparin in the first trimester and warfarin thereafter and this protocol is widely recommended.

Introduction: Many young women in India suffer with valve disease and undergo replacement procedure both before and after marriage. Rheumatic heart valve disease continues to be widespread amongst rural and semi-urban north Indian population Women residing in these part of North India with mechanical heart valves on anticoagulants having pregnancy itself comes under a bracket of High Risk and brings out a unique challenge in their management at tertiary centre despite the standard of maternal and cardiac care is systematic and easily available to all. Despite improvements in general education girl child is still neither favoured in pregnancy nor in sickness. We have studied the effects of uniqueness this social problem and its impact of the pregnancy outcomes. Clinical Methods and Material: Study Patients This is a eleven year experience of prospective observational study in patients operated and managed by a single surgeon between April 2002- till May 2013. Six-hundred and eighty three married young women aged between 19-35 years (child bearing age) received mechanical prosthetic valves either single or double valve. Of these 656 women, 69 (10.5 %) were lost to follow-up and 27 (3.9 %) died within 30 days of operation. The median regular follow-up of 587 survivors was 6.5 years. Management during Pregnancy Patients were managed jointly by the department of Cardiovascular and Thoracic Surgery and the department of Maternal and Reproductive Health (MRH) of the same hospital 1st Trimester: Discontinue oral Nicoumalone completely and start on Unfractionated Heparin. 2nd and 3rd Trimester : Continue oral Nicoumalone (until week 36). 36th week onwards (Prior to delivery): Heparin only till delivery. Post Partum Period: Start anticoagulants along with Heparin, 6 hours after delivery. Results: A. Outcomes of pregnancy: {Fig 1}

Distribution of pregnancy outcome in pregnancy with valve replacement

50 45 40 35 30 25 20 15 10 5 0 successful pregnancies abortions still births 2 21 46

No of patients

Outcome

Fig 1 : showing 46 (64.31%) women had successful deliveries and 23 (37.68%) had single or repeated abortions or stillbirth.

B. Mode of delivery: Fig 2

Mode of delivery
35

30 27 25

no. of patients

20

19

15

10

0 LSCS NVD

Mode of delivery

Fig 2 : showing a higher incidence of section was due to obstetrical reasons. Fetal indications like IUGR and foetal distress formed a major indication where 19 women had LSCS and 27 had normal vaginal delivery. C. Fetal complications

ICH
Anomaly DNB Fetal distress Preterm delivery IUGR No complications 0 5 10 15 20

Fig 3: Higher incidence of fetal problems were inherent to the general nutritional status of the mother, effect of medication they were on and the side effects. D. Maternal complications and associated medical disease : Different life threatening maternal complications were encountered in these pregnant women and were managed effectively, being cared in tertiary situations. Discussion: Pregnancy is a hypercoagulable state with a higher risk of thromboembolic complication during pregnancy with maternal mortality 1% - 4%.(1) Mechanical heart valves are inherently prone for increased thromboembolic events and acute hemodynamic problems due to mechanical dysfunction caused by valve thrombosis and pannus formation. Advanced heart disease associated with poor knowledge about pregnancy related issues, appropriate maternal care during pregnancy, malnutrition, increased pulmonary artery pressures, high incidence of right-sided valve and ventricular dysfunction along with chronic Atrial fibrillation also posses a greater challenge in these patients. The problems associated in management of these patients are awareness, compliance and complications associated with anticoagulation. This is associated with increased foetal wastage. In our series, the foetal wastage among women receiving anticoagulants was 37.68% .There is increased risk of warfarin embryopathy when used during the first trimester with continuing risk of central nervous system damage throughout pregnancy. (2-4) Heparin is safer for the fetus as it does not cross the placenta but carries a high risk of fetal loss

from retro-placental haemorrhage as well as maternal bleeding complications. Heparin instead of warfarin has been recommended for use during the first trimester and after the 36th week but long-term heparin is not without any complications.( 5-8) A review of reported experiences are summarized in Table: 1 Larrea et al reported a lower incidence of fetal complications in women receiving intravenous heparin in the first trimester and warfarin thereafter than in those taking warfarin throughout but at the expense of increased maternal mortality(9) In our present series mild embryopathy occurred in 5 (13.95 %) of the 43 successful pregnancies where as the incidence of embryopathy is lower with use of IV unfractionated heparin in the first 3 months (during 6th to 12th weeks of pregnancy). ( 10 )

TABLE 1: Review of literature on outcome of pregnancies in patients with prosthetic heart valves Our Study Total pregnancy Succesful births Abortions Valve thrombosis 69 43(62.3%) 21(30.43%) 0% Oakley et al 62 61(98.4%) 1(1.6%) 4(6.5%) Pawan Kumar et al 47 40(85.5%) 7(14.9%) 2(4.2%) Larrae et al 47 36(76.6%) 11(23.4%) 3(7.9%)

Western studies reveal a good outcome of pregnancy in majority of women with prosthetic heart valves as compared to our series where abortion rates are more due to poor nutrition, compliance and low socioeconomic status . Heparin is neither effective nor safe for long-term use in pregnancy because of risk of both thromboembolism and bleeding with hazard to mother and fetus However the use of heparin during pregnancy does not result in a better outcome of pregnancy ( 5 ) In 135 published cases, the infants in one-eighth were stillborn, in one-fifth premature (a third of whom died) and at most, apparently normal in two-thirds. The fetal outcome was slightly better in women taking the combination of heparin in the first trimester and warfarin thereafter and this scheme is widely recommended. Maternal thrombo-embolism is a problem. This is particularly important during pregnancy when the concentration of most coagulation factors in the blood is increased and fibrinolysis is decreased (11-13) Satisfactory anticoagulation is mandatory. It is worth noting that in our series none of the women were observed with Valve thrombosis as improvement in one aspect occurs at the cost of the other.

Conclusion: Decision regarding anticoagulation in pregnancy requires intense counseling done at multiple sittings in terms of complete prospective follow-up to predict the efficacy and safety of any regime in pregnancy. Thus risk is associated with inadequate dosing and monitoring. Meticulous monitoring must be emphasized which Underscores the need to develop local innovative solutions for local problems in vast and varied country like India. References: 1. Chan WS, Arch Int Med 2000; 160(2): 191 Med 1916. 2. Hall JG. Embryopathy associated with oral anticoagulant therapy. Birth Defects. 1965; 12: 133140. 3 3. Sahul WL, Emery H, Hall JG. Chondrodysplasia punctata and maternal warfarin use during pregnancy. Am J Dis Child. 1975; 129: 360362. 4. Hall JAG, Paul RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med. 1980; 68: 122140. 5. Hall JG, Pauli RM, Wilson KM. Maternal and foetal sequelae of anticoagulation during pregnancy. Am J Med, 1980; 68: 122-40. 6. Harrison EC, Roschke EJ. Pregnancy in patients with cardiac valve prostheses. Clinical Obstetrics and Gynaecology, 1975; 18: 107-23. 7. Hirsh J, Cade JF, O'Sullivan EF. Clinical experience with anticoagulant therapy during pregnancy. Br Med J, 1970; 1: 270-3. 8. Hirsh J, Cade JF, Gallus AS. Anticoagulants in pregnancy: A review of indications and complications. Am Heart, 1972; 83: 301-5 9. Larrea JL, Nunez L, Reque JE, Gil Aguado M, Matarros R, Mingues JA. Pregnancy and mechanical valve prostheses is a high risk situation for the mother and the fetus. Ann Thorac Surg 1983;36:459-63. 10. Chan WC, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical valves: a systemic review of the literature. Arch Int Med. 2000;160: 191196.) 11.Shaper AG, Macintosh DM, Evans CM, Kyobe J. Fibrinolysis and plasminogen levels in pregnancy and the puerperium. Lancet, 1965; 2: 706-8. 12.Todd ME, Thompson JH, Bowie ETW, Owen CA. Changes in blood coagulation during pregnancy. Mayo Clin Proc, 1965; 40: 370-83. 13. Brakman P. The fibrinolytic system in human blood during pregnancy. Am J Obstet Gynaec,1966; 94: 14-20.