Pulmonary hypertension: diagnosis and managementBMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f2028 (Published 16 April 2013) Cite this as: BMJ 2013;346:f2028
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We are grateful to Dr Morton for emphasizing the importance of contraception in women of childbearing age with pulmonary hypertension. In particular, for highlighting hysteroscopic insertion of a micro-insert system (Essure) as a potentially preferred method of sterilization. We discussed pregnancy and contraception in our review but welcome the opportunity to address this topic in more detail in response to Dr Morton’s comments.
We accept and indeed have noted that maternal mortality is high, but this has improved over the period of the last decade, and is estimated at between 17-33% 1. We agree that the risks are particularly high in the immediate post-partum period but deterioration during the first two trimesters without intervention is associated with an extreme risk of death reflecting an inability to meet the cardiac demands of pregnancy 2. In this setting surgical termination may be associated with cardiovascular collapse but in more stable patients, surgical termination can be performed safely in experienced hands. However, the emotional effects of termination should not be underestimated in this vulnerable population.
Consequently women are counseled regarding these high risks 3 but key in this process is the ability to offer a choice of contraception and to recognize that the needs of individual patients and the motivation behind decisions will be varied. Given the high maternal mortality the optimal approach should provide high levels of efficacy with usual rather than perfect use.
We agree that progesterone only, are preferred to oestrogen containing contraceptives and with perfect use all are highly effective. Etonogestrel implants have the benefit of not requiring compliance with 12 weekly injections, which is a limitation of intramuscular medroxyprogesterone and remembering to take oral desogestrel daily. Nonetheless some patients prefer to take oral medications over injections and others do not like the idea of an implant. It should also be noted that intramuscular injections can be given safely to patients on oral anticoagulation and indeed many of our patients have successfully used this form of contraception.
The levonorgestrel releasing intrauterine coil is highly effective as a form of contraception and also has the advantage of reducing the heaviness of menstrual periods, which are frequently seen in women on warfarin and sildenafil (which can cause vascular engorgement). We appreciate that a vagal response can occur at the time of insertion and failure to recognize this can cause cardiovascular collapse. However, insertion in a hospital environment, as recommended in our review, by practitioners familiar with these patients dramatically minimizes these risks.
Surgical sterilization is less effective than the perfect use of other methods described above but may be considered in patients with pulmonary hypertension at the time of Caesarean section in appropriately counseled patients. Hysteroscopic insertion of a micro-insert system offers the prospect of a permanent method of contraception and has been suggested as a “preferred” method of contraception. For some patients, particularly young women presenting for the first time with a new diagnosis of pulmonary hypertension the concept of an irreversible form of contraception may not be acceptable or appropriate. Indeed, we have managed patients with chronic thrombo-embolic pulmonary hypertension who have presented with severe disease which has been cured by pulmonary endarterectomy and who have gone on to have subsequent successful pregnancies.
Dr Morton has also helpfully raised the importance of interactions between treatment for pulmonary arterial hypertension and hormonal contraceptive preparations, namely that the endothelin receptor antagonist bosentan is an enzyme inducer. This is not an issue with intramuscular medroxyprogesterone due to the high doses of progesterone but this interaction is important with oral desogestrel where we would advise taking double dose or in patients receiving the etonogestrel implant the option would be to add oral desogestrel or insert 2 implants. In addition, increasing the dose of emergency hormonal contraception is essential. Ambrisentan, an alternative endothelin receptor antagonist, which is not an enzyme inducer can be used in women of childbearing age and avoids these interactions.
Finally, it should be recognized that despite the high risks of pregnancy some women with pulmonary hypertension will decline contraception and actively plan pregnancy. These patients should be recognized and supported and managed in specialist centres where the chance of a positive outcome can be maximized 4.
In summary many of the contraceptive needs of women with pulmonary hypertension are similar to women in general and choice is key to ensuring adherence and efficacy. The major difference is that the price of contraceptive failure in pulmonary hypertension is very high. Access to family planning advice by specialists experienced with this group of patients is therefore key and is a further advantage of having a network of specialized pulmonary hypertension centres.
1 Bedard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J 2009; 30:256-265.
2 Kiely DG, Condliffe R, Wilson V, Gandhi S, Elliot C. Pregnancy and pulmonary hypertension: a practical approach to management. Obsteric Medicine 2013 (in press).
3 Kiely DG, Elliot CA, Webster VJ, Stewart P. Pregnancy and pulmonary hypertension: new approaches to the management of a life threatening condition. In: Steer PJ, Gatzoulis MA, Baker P, editors. Heart Disease and Pregnancy. London: RCOG Press; 2006. pp. 211–29.
4 Kiely DG, Condliffe R, Webster V, et al. Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach. BJOG 2010; 117:565-574
Competing interests: No competing interests
I thank Kiely et al for their comprehensive review of the diagnosis and management of pulmonary hypertension (PH).1 An important aspect of management not addressed in their review is advice regarding contraception. A significant proportion of subjects with PH are women of child-bearing age, whose disease may be idiopathic, or secondary to connective tissue disease or congenital heart disease. PH in pregnancy is associated with a 25-56 % maternal mortality, the risk of death being greatest peripartum. Surgical termination in second trimester may be associated with critical cardiovascular collapse. Bosentan and warfarin are teratogenic.
Contraception advice for women with PH is complex.2,3 Oestrogen containing contraceptive medication is avoided because of increased risk of thromboembolism. Due to enzyme induction bosentan may reduce the efficacy of etonorgestrel (Implanon) implants. The risk of contraceptive failure is high with progestogen-only contraceptive pills. Surgical sterilisation in young women is associated with higher late failure rates with the risk of ectopic pregnancy as well as the risk of vagal reaction at the time of the procedure. Surgical sterilisation and the insertion of the levonorgestrel-releasing intrauterine device (Mirena) may also be asssociated with vagal reactions and cardiovascular collapse. The need for strict compliance with 12 weekly injections and the risk of intramuscular haemorrhage in subjects treated with warfarin may make Depo-Provera less desirable. Vasectomy may not be appropriate for the male partner of women with PH as he may outlive her and wish to father children in a subsequent relationship.
Overall hysteroscopic insertion of a micro-insert system (Essure) may be the preferred method of sterilisation for women with PH.4 The procedure may be performed without anaesthetic, though contraceptive methods must be continued for 3 months afterwards until permanent tubal occlusion is confirmed radiologically.
1. Kiely DG, Elliot CA, Sabroe I, Condliffe R. Pulmonary hypertension: diagnosis and management. BMJ. 2013 ; 16:346:f2028.
2. Lara B, Fornet I, Goya M, López F, De Miguel JR, Molina M et al. Contraception, pregnancy and rare respiratory diseases. Arch Bronconeumol. 2012 ;48:372-78.
3. Thorne S, Nelson-Piercy C, MacGregor A, Gibbs S, Crowhurst J, Panay N et al. Pregnancy and contraception in heart disease and pulmonary arterial hypertension. J Fam Plann Reprod Health Care. 2006; 32:75-81.
4. Hemnes AR, Robbins IM. Hysteroscopic sterilization in women with pulmonary vascular disease. Mayo Clin Proc. 2008 ;83:1188-89.
Competing interests: No competing interests
We have read with interest the review article by Kiely et al.1 and would like to shares some thoughts and comments regarding the importance, challenges and objectives to meet proper global education and training for physicians treating pulmonary hypertension (PH). We think that education and training during internal medicine residency programs, pulmonary and cardiovascular diseases fellowship programs on PH has lagged behind the dramatic therapeutic advances achieved for diverse forms of PH in the last 25 years.2 Global education in PH should include training objectives at different levels (the generalist, the general specialist and the PH specialist), requiring substantial organization and effort.
Deano et al. 3 determined the accuracy of PH diagnoses in three PH referral centers of excellence, finding a significant number of patients being misdiagnosed, misclassified and prescribed inappropriate PH-specific therapies. A survey of 453 physicians (94% of them pulmonologists) found that approximately 30% of physicians did not perform right heart catheterization (RHC) for definitive diagnosis of PH prior to initiation of PH-specific therapies, basing their diagnoses only on echocardiographic findings.4 As emphasized in PH current guidelines5, physicians should refer patients early in the diagnostic work-up to PH referral centers, even if the work-up is incomplete, since delayed referrals to PH centers has been a continuing problem. We believe that despite some efforts, the issues of global education and training for generalists and general specialists (pulmonologists and cardiologists) continues to be very limited for PH and more intensive and targeted initiatives are needed.
1. Kiely DG, Elliot CA, Sabroe I, Condliffe R. Pulmonary hypertension: diagnosis and treatment. BMJ 2013;346:f2028.
2. Elliott CG, Barst RJ, Seeger W, Porres-Aguilar M, Brown LM, Zamanian RT, Rubin LJ. Worldwide physician education and training in pulmonary hypertension: Pulmonary vascular disease: the global perspective. Chest 2010;137:Suppl 6: 85S-94S.
3. Deano RC, Glassner-Kolmin C, Rubenfire M, Frost A, Visovatti S, McLaughlin VV, Gomberg-Maitland M. Referral of patients with pulmonary hypertension diagnoses to tertiary pulmonary hypertension centers. JAMA Intern Med 2013; Apr 8:1-7. doi: 10.1001/jamainternmed.2013.319. [Epub ahead of print]
4. Minai OA, Nathan SD, Hill NS, Badesch DB, Stoller JK. Pulmonary hypertension in lung diseases: survey of beliefs and practice patterns. Respir Med 2010;104:741-748.
5. McLaughlin VV, Archer SL, Badesch DB, et al. American College of Cardiology Foundation/American Heart Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report from the American College of Cardiology Foundation Task Force on expert consensus documents and the American Heart Association. Circulation 2009;119:2250-2294.
Competing interests: No competing interests