CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 326 AFRICA about 2 468 pregnancies and 1 874 women.31 Only 46 titles were eligible and included in the final analysis.31 This was mainly due to widespread heterogeneity and strict inclusion criteria. The authors further noted that a serious limitation of the metaanalysis was the high degree of bias between studies.31 In this analysis, almost 30% of the studies reported the older ball-and-cage type valves.31 Contemporary practice has advocated a move away from the highly thrombogenic ball-andcage valves to the newer single tilting or bi-leaflet type.34 The Starr Edwards ball-in-a-cage valves are now obsolete and production was stopped in 2007.34 It is to be noted that over half a million of these valves were implanted from 1960 to 2007, with about 300 000 implanted in the last seven years of its production.34 The main problem with this valve was the formation of pannus and the inability to accurately measure gradients due to its unique non-central flow. The meta-analysis further failed to risk-stratify patients in terms of valve type, primary valvular disease and valve position. Only 26% of studies highlighted whether the primary valvular pathology was rheumatic or congenital in origin.33 Few studies used UFH and LMWH.33 This reflects a deficiency in the literature, as the heparins confer a safety benefit to the foetus since it does not cross the placenta. D’Souza et al. reported a TEC risk in pregnant women on VKA as only 2.7% (1.4–4.0).31 This risk increased to 5.8 % (3.8– 7.7) in women using sequential therapy, 8.7% (3.9–13.4) in women on LMWH and 11.1% (2.8–19.6) in women on UFH.33 With VKAs, sequential treatment and LMWH, maternal mortality occurred in 0.9% (0.4–1.4), 2.0% (0.8–3.1) and 2.9% (0.2–5.7), respectively, live births in 64.5% (48.8–80.2), 79.9% (74.3–85.6) and 92.0% (86.1–98.0), respectively, and anticoagulant-related foetal/neonatal adverse events (embryopathy or foetopathy) in 2.0% (0.3–3.7), 1.4% (0.3–2.5) and 0%, respectively.31 Steinberg et al. conducted a systematic review and metaanalysis in 2016 with the goal of including studies using adjusted doses for UFH and LMWH, dependent on aPTT and anti-Xa targets, respectively.1 It is now well known that the use of LMWH without monitoring can lead to catastrophic TEC.1 Furthermore they wanted to reflect a more contemporary population and excluded studies with > 10% use of the older, more thrombogenic ball-and-cage prostheses.1 They further attempted to elucidate whether foetal risk with warfarin is dose dependent.1 Previous studies with low-dose warfarin < 5 mg showed warfarin to be less teratogenic in comparison to higher doses. Furthermore, they found no significant difference in foetal risk observed between women taking < 5 mg daily warfarin and those on a LMWH regimen (risk-adjusted ratio: 0.9; 95% CI: 0.3–2.4).1 In addition, they only included studies where the valve position was documented, and excluded the right-sided tricuspid and pulmonary valves.1 However, they did not capture data on primary valve pathology and the presence of RHD, which is of relevance in Africa and LMIC. The meta-analysis focused on studies that shared a very similar geographical cluster and this may inadvertently have affected outcome data. Adverse events could not be stratified according to trimester as this information was not readily available. This is important as bridging with heparins normally occurs in the first trimester and in the two weeks prior to planned delivery (Fig. 4). A variability of 44% (95% CI: 18–82%) for averaged risk estimates of maternal composite and 81% (95% CI: 67–90%) for averaged risk estimates for foetal composite outcome was reported. This variability was the result of a significant degree of heterogeneity between studies. Of interest is that this metaanalysis reported a much lower risk of adverse maternal outcome with dose-adjusted LMWH than previously reported. Both these meta-analyses showed that VKA had the fewest maternal complications but also the fewest live births. In contrast, LMWH was associated with more live births but an increase in maternal complications. Author recommendations The authors’ current practice is in line with some of the discussions above, and is as summarised in Figs 5 and 6. • The option of MHV vs BPV should be discussed with women desiring fertility, if available • Pros and cons of both valves should be discussed • If wanting to delay pregnancy preferably offer non-hormonal LARC • If MHV, counsel to continue VKA until pregnancy achieved • Counsel to book her first antenal appointment at first missed period • Cardiology assessment • Risk stratify by primary valve pathology, valve type and valve position • Offer ECG and echocardiography • Treat co-morbidities • Identify obstetric risks, e.g. history of pre-eclampsia, pre-term labour • Start folic acid • Continue RHD prophylaxis with oral penicillin • Lifestyle changes, smoking cessation Prenatal first trimester • Expert centre for pregnancy and cardiac disease • Counsel on maternal and foetal risks associated with cardiac disease and pregnancy (see Fig. 6) • Discuss and offer regimens for anticoagulation (see Fig. 5) • Use shared decision-making approach with extensive counselling of all risks and benefits with each regimen • Echocardiography: to assess the performance of the prosthetic valves, assess the systolic function, pulmonary pressures and to look for any new valvular heart disease that may require treatment • Bridge to IV UFH at 36 weeks (if on warfarin) or 37 weeks (if on dose-adjusted LMWH) • Manage in an obstetric high care • Vigilant monitoring for possible complications (see Fig. 6) • Routine non-invasive blood pressure, pulse, oxygen saturation, respiratory rates and 3-lead ECG • Routine intravenous antibiotics for 24 hours are administered for RHD prophylaxis • Anticoagulation can be restarted 4-6 hours post normal vaginal delivery • Anticoagulation can be delayed up to 12 hours post caesarean section. This is to ensure that the risk of bleeding is reduced • A fine balance between bleeding and thrombosis risk must always be considered • IV UFH is generally used again to bridge women back to warfarin • Basic postpartum care such as breastfeeding, contraception, counselling on pre-pregnancy clinic for future pregnancies and cardiology follow-up appointments should be made. Antenatal Peripartum MHV: mechanical heart valves, BPV: bio-prosthetic valves, LARC: long-acting reversible contraception, VKA: vitamin K antagonists, ECG: electrocardiogram, RHD: rheumatic heart disease, IV UFH: intravenous unfractionated heparin, LMWH: low-molecular weight heparin Fig. 5. Author recommendations for anticoagulation in pregnant women with mechanical heart valves at Inkosi Albert Luthuli Central Durban, South Africa.
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