Heart Disease in Pregnancy - part 10 pps

Table 23.1 Typical failure rates Pearl index of contraceptive methods pregnancies per 100 women-years of use Method ‘Typical’ failure rate ‘Best use’ failure rate No contraception used b

Pulmonary hypertension

Primary pulmonary hypertension usually occurs as a sporadic condition, with apredominance of women, but occasional families showing autosomal domi-nant inheritance have been reported.24It has been found to be caused by the

BMPR2 gene on chromosome 2.25

Autoimmune disorders

Autoimmune disorders have been discussed in Chapter 11 Most of them arenot inherited as single gene disorders, but often show familial aggregations.However, they may have a direct clinical effect on the fetus as, for example, insystemic lupus erythematosus (SLE) SLE is an autoimmune disorder with amarked female predominance The heart is involved in up to 25% of cases, inthe form of pericarditis with or without pericardial effusion Cardiac symptoms

do not necessarily predominate, the disease being a multisystem disorder, butaffected women can have significant obstetric problems, including recurrentmiscarriages, pre-term labour and an exacerbation of symptoms during preg-nancy Offspring of affected mothers may have complete heart block requiringsupportive treatment in the neonatal period These problems appear to resultfrom the passage of autoantibodies across the placenta

Table 22.2 General recurrence risks in congenital heart disease

Percentage risk

Half-sibling or second-degree relative 1–2

Offspring of isolated case:

Two affected siblings (or sibling and parent) 10

More than two affected first-degree relatives 50

Table 22.3 Offspring risks for specific congenital heart lesions

Ventricular septal defect 9.5 2.5

Persistent ductus arteriosus 4 2

Hypertrophic cardiomyopathy is frequently inherited as an autosomal nant disorder The onset of symptoms is usually in early adult life rather than inchildhood It may cause sudden arrhythmia Early diagnosis can lead to effec-tive treatment There are now a number of genes identified including cardiacbeta-myosin heavy chain gene, the cardiac troponin T gene, and the alpha-tropomyosin gene.26,27Fetal echocardiography will not recognize the adult-onset cardiomyopathies and prenatal diagnosis will depend on identifying thecausative mutation in the family Preconceptual referral to a specialized centerwould be recommended

domi-Idiopathic dilated cardiomyopathy is also a heterogeneous group of ders, but occasionally may show an inherited pattern Most families are con-sistent with autosomal dominant inheritance, although occasional familieswith autosomal recessive inheritance and X-linked inheritance have been re-ported.28,29The variability in expression may also make counseling difficult.Review of the family history may help elucidate the inheritance pattern, but

disor-in small families it is often considered best to offer echocardiographic ing of all first-degree relatives to detect occult disease

screen-Coronary artery disease and myocardial infarction

Coronary heart disease has numerous causes, both genetic and environmental

It is rarely cited as a cause for concern in terms of risk to offspring However, milial hypercholesterolemia is an autosomal dominant disorder that is consid-ered to account for about 10–20% of early coronary heart disease and, if this hasbeen diagnosed in a parent, it is worth considering testing the children, so thatearly preventive measures can be introduced Although the risk of inheritingthe gene is 50% in such families, the risk of heart disease is considerably lessthan this, as a result of multiple confounding factors The basic defect in familialhypercholesterolemia is a low-density lipoprotein receptor deficiency, and thegene is located on chromosome 19 Mutations have been identified in manycases, and provide an accurate means of screening in some families.30

fa-References

1 Kelly TE Clinical Genetics and Genetic Counseling Chicago: Year Book, 1986.

2 Holt M, Oram S Familial heart disease with skeletal malformations Br Heart J

1960;22:236–42.

3 Hurst JA, Hall CM, Baraitser M Syndrome of the month: the Holt–Oram syndrome

J Med Genet 1991;28:406–10.

4 Li QY, Newbury-Ecob RA, Terrett JA et al Holt–Oram syndrome is caused by

mutations in TBX5 — a member of the Brachyury (T) gene family Nat Genet 1997;15:

21–9.

5 Tartaglia M, Mehler EL, Goldberg R et al Mutations in the protein tyrosine

phos-phatase gene PTPN11 cause Noonan syndrome Nat Genet 2001;29:465–8.

6 Sharland M, Burch M, McKenna WM, Patton MA A clinical study of Noonan

syn-drome Arch Dis Child 1992;67:178–83.

7 Sarkozy A, Conti E, Diglio MC et al Clinical and molecular analysis of 30 patients with

multiple lentignes LEOPARD syndrome J Med Genet 2004;41;e68.

8 Milewicz DM, Pyeritz R, Crawford ES, Byers PH Marfan syndrome: defective tion, synthesis and extracellular matrix formation of fibrillin by cultured dermal

secre-fibroblasts J Clin Invest 1992;89:79–86.

9 Ward OC A new familial cardiac syndrome in children J Irish Med Assoc 1964;

54:103–6.

10 Splawski I, Shen J, Timothy KW et al Spectrum of mutations in long QT syndrome

genes KVLQT1, HERG, SCN5A, KCNE1 and KCNE2 Circulation 2000;102:1178–

85.

11 Jervell A, Lange-Nielsen F Congenital deaf-mutism, functional heart disease and

prolongation of Q–T interval and sudden death Am Heart J 1957;54:59–68.

12 Schmidt MA, Ensing GJ, Michels VV, Carter GA, Hagler DJ, Feldt RH Autosomal

dominant supravalvular aortic stenosis: large three-generation family Am J Med

Genet 1989;32:384 –9.

13 Nickerson E, Greenberg F, Keating MT, McCaskill C, Shaffer LG Deletions of the

elastin gene at 7g11.23 occur in 90% of patients with Williams syndrome Am J Hum

Genet 1995;56:1156–61.

14 Ellis RWB, Van Creveld S A syndrome characterised by ectodermal dysplasia,

poly-dactyly, chondro-dysplasia and congenital morbus cordis Arch Dis Child 1940;

15:65–84.

15 Ruiz-Perez VL, Tompson SW, Blair HJ et al Mutations in two non-homologous genes

in a head-to-head configuration cause Ellis–van Creveld syndrome Am J Hum Genet

(Kartagener syndrome) Am J Hum Genet 2001;68;1030–5.

18 Ryan AK, Goodship JA, Wilson DI et al Spectrum of clinical features associated with

interstitial chromosome 22q11 deletions: a European collaborative study J Med Genet

1997;34:798–804.

19 Dennis NR, Warren J Risks to the offspring of patients with some common

congeni-tal heart defects J Med Genet 1981;18:8–16.

20 Emanuel R, Somerville J, Inns A, Withers R Evidence of congenital heart disease in

the offspring of parents with atrioventricular defects Br Heart J 1983;49:144 –7.

21 Zellers TM, Driscoll DJ, Michels VV Prevalence of significant congenital heart defects

in children of parents with Fallot’s tetralogy Am J Cardiol 1990;65:523–6.

22 Harper PS Practical Genetic Counselling, 6th edn Oxford: Butterworth-Heinemann,

2004.

23 Nora JJ, Berg K, Nora AH Cardiovascular Diseases Genetics, epidemiology and prevention.

Oxford: Oxford University Press, 1991.

24 Thompson P, McRae C Familial pulmonary hypertension: evidence of autosomal

dominant inheritance Br Heart J 1970;32:758–60.

25 Lane KB, Machado RD, Pauciolo MW et al Heterozygous germline mutations in BMPR2 encoding TGF-beta receptor cause familial primary pulmonary hyperten-

sion Nat Genet 1998;26:81–4.

26 Geisterfer-Laurence AAT, Kass S, Tanigawa G et al A molecular basis for familial

hypertrophic cardiomyopathy Cell 1990;62:999–1006.

27 Elliott P, McKenna WJ Hypertrophic cardiomyopathy (review) Lancet 2004;363:

1881–91.

28 Berko BA, Swift M X-linked dilated cardiomyopathy N Engl J Med 1987;316:

1186–91.

29 Muntoni F, Cau M, Ganau A et al Deletion of muscle promotor region associated with

X linked dilated cardiomyopathy N Engl J Med 1993;329:921–5.

30 Goldstein JL, Hobbs HH, Brown MS Familial hypercholesterolemia In: Scriver CR,

Beaudet AL, Sly WS et al (eds), The Metabolic and Molecular Bases of Inherited Disease,

8th edn London: McGraw-Hill, 2000.

advan-When should contraceptive advice be given?

Arguably, all women should have access to appropriate contraceptive advicebefore they choose to become sexually active This is especially true of womenwho have a medical condition (in this case, cardiac disease) in which pregnancyrepresents a particular risk Improved nutrition and the liberalization of manysocieties have led to a dislocation of the age at which women become sexuallymature and able to conceive (which can be as early as 11 or 12 years of age), theage at which they can legally become sexually active (commonly 16 years ofage) and the age at which their parents would expect them to become sexuallyactive (which may be some years later) Thus, it can be difficult for the cardiolo-gist to know when to start introducing the idea of contraception into their con-sultations The appropriate time will vary according to the individual needs ofthe woman, and the society in which she lives

327

Copyright © 2007 by Blackwell Publishing

My personal view is that basic sex education, including knowledge of ception, should have been given by the time a woman is able to become preg-nant This is not to encourage her to undertake sexual activity earlier (indeed,there are many advantages to delaying sexual activity until the woman is psy-chologically mature enough to cope with long-term relationships, not the least

contra-of which includes reducing the risk contra-of sexually transmitted infection and tility), but to empower young women in situations in which she may be coerced

infer-by a partner or even her family into an early sexual relationship Ideally, mation about contraception should be embedded in a broader education aboutpersonal relationships and responsibilities In the personal view of the author,all cardiologists providing pediatric cardiology services should arrange to assessand plan the contraceptive education needs of their patients when they reachabout 12 years of age, and either provide information themselves, or arrange for

infor-an appropriate professional with a knowledge both of contraception infor-and heartdisease to provide it instead Ideally, the family of the very young woman withheart disease should be involved in this process, especially her mother How-ever, the rights of the patient herself take precedence over the family view ifthese are at odds

Contraceptive advice can profitably be given at the same time as a discussionwith the woman about the long-term impact of her cardiac condition on herlongevity, lifestyle and child-bearing potential I have personally come acrossmany women who have been given inadequate or misleading advice about thelong-term prognosis for their condition (often in an understandable attempt toprotect a young and optimistic woman from the sobering appreciation of theimplications of her condition) or the risk to them of becoming pregnant Somehave happily embarked on a pregnancy, only to be faced with a substantial risk

of death if they continue to term, or the emotionally traumatic alternative oftermination of pregnancy

The normal female desire to have children is not generally lessened by havingheart disease and, for some women, this may lead them to choose surgical repair

of their condition earlier than is otherwise necessary, so as to reduce the risk ofpregnancy Alternately, she may choose to delay child bearing until after sur-gery becomes necessary on medical grounds In other women, their conditionwill deteriorate as they get older, and they may need to be advised to have theirchildren as early as relationships allow

Discussing these difficult issues in a sensitive and supportive manner requiresskill, patience and understanding It is vital that the patient’s values are consid-ered paramount, not those of physicians or her family All too often the woman

is presented by one or both of these groups with views that either minimize potential hazards or exaggerate them The excuse is that this is ‘in the patient’sbest interests’ There is only one attitude that is in the best interests of thewoman concerned, and that is to tell her the truth She has a right to be pre-sented with as accurate a prognosis as possible for both mother and baby whenpregnancy is discussed, and to be given an account of any potential hazards of

procedures for contraception and sterilization The woman who is aware thatshe may die within a few years may, at the extremes, have one of two diametri-cally opposed attitudes One is that, if she is going to die, she would not want toleave a young child on his or her own, in the care of others The other is that shewould have done a good job in producing a healthy baby, who, if the motherdies, will live on, develop and be a credit to her memory Many women will find

it very hard to make a choice between these two alternatives and, for them, tensive counseling may be necessary

ex-The effectiveness of contraceptive methods

The failure rate of any particular method of contraception is expressed using the

‘pearl index’, which is the number of pregnancies that occur per 100 years of use It should be borne in mind that there is a ‘typical’ failure rate based

women-on the experience of the average user, and a ‘best use’ failure rate based women-on theoptimal use of the technique For some methods, these will be very different(e.g the effectiveness of the use of condoms is very dependent on how well theyare used) whereas for others, such as the IUCD, there is essentially no user-dependent component and therefore no difference in the failure rates Typicalfailure rates for the various methods are shown in Table 23.1

Table 23.1 Typical failure rates (Pearl index) of contraceptive methods (pregnancies per

100 women-years of use)

Method ‘Typical’ failure rate ‘Best use’ failure rate

No contraception used by normally fertile couple 85 85

Combined oral contraceptive pill 5 <1

Daily low-dose oral progestogen 5 2

Depot Provera (intramuscular injection of a <1 <1

progestogen)

Progestogen implants (e.g Norplant) <1 <1

Vaginal hormonal ring (e.g Nuvaring) Not yet established <1

Methods available that have no direct influence on

heart disease in the woman

‘Natural’ methods

There are a variety of techniques that use our understanding of how conceptionoccurs to try to prevent pregnancy Although often called ‘natural’, many seemfar from natural in practice, e.g abstinence is completely effective but for manydefeats the purpose of having a relationship! The so-called ‘safe period’ relies onthe assumption that the average woman ovulates 14 days from the beginning ofher last menstrual period Conception usually occurs only if intercourse takesplace around the time of ovulation (sperm can remain viable for up to 72 hoursand the egg for about 24 hours before fertilization occurs) Unfortunately, manywomen have irregular cycles and so they cannot rely on timing alone There arevarious devices measuring temperature (the woman’s temperature rises byabout 0.5°C after ovulation as a result of secretion of progesterone from theovary) or the viscosity of the cervical mucus These methods can usually detectwhen ovulation has occurred, and intercourse more than 48 hours after ovula-tion is unlikely to result in a pregnancy until after the next period

The likelihood of conception for each act of intercourse before the next strual period is only about 1% Unfortunately, ovulation does not always occurreliably 14 days after the beginning of the menstrual period, and sometimes occurs even as early as day 5 (occasionally, even before the menstrual flow hascompletely stopped) Thus, the likelihood of conception between the end of theperiod and day 12 is about 4% for each act of intercourse This means that pen-etrative intercourse is relatively safe for only about 10 days a month, and manycouples find this irksome (it is sometimes known as the ‘rhythm and blues’method) The temperature method is prone to disruption if the woman becomes pyrexial, e.g from a cold, and many women find obtaining a goodsample of cervical mucus difficult

men-Barrier contraception

Male withdrawal before each ejaculation is often emotionally unsatisfactory forboth partners It is also often difficult for the male partner to time withdrawalaccurately so that ejaculation occurs before he has withdrawn In addition, asmall number of sperm are often released into the vagina before orgasm and fullejaculation, and pregnancy can occur if even a single sperm reaches the egg Forall these reasons, the failure rate of this technique is usually unacceptable forwomen for whom pregnancy presents serious risks

Male and female condoms have the advantage that they protect against ually transmitted infections (STIs) However, they require considerable skill touse correctly, and many couples fail to acquire adequate instruction Many cou-ples find that male condoms interfere with the spontaneity of sexual inter-course Both female condoms and diaphragms can be inserted well in advance

sex-of intercourse, but require premeditation Female condoms are made sex-ofpolyurethane rather than latex or rubber, and make rustling noises in use,

which some people find offputting! All of these methods should be used gether with a spermicide (most of which contain nonoxynol-9) if optimum success in preventing pregnancy is to be obtained However, all of them haverelatively high failure rates Whether they are suitable for use by couples where the woman has heart disease therefore depends critically on how impor-tant it is to avoid pregnancy If effectiveness is a priority, then clearly these tech-niques are not appropriate.

to-Cervical caps have to be individually fitted for each woman and cover onlythe cervix, rather than sitting between the posterior fornix and the retropubicvagina as shown for the diaphragm in Figure 23.1 They are difficult to use cor-rectly and are no longer widely available

Lactational amenorrhea

In technologically undeveloped communities, prolonged breast-feeding is atraditional method of spacing pregnancies The optimum time interval betweenpregnancies, in terms of minimizing the risk of ectopic pregnancy, miscarriageand placenta praevia, is 2 years This probably relates to changes in the vascularsupply to the uterus Pregnancy increases blood flow to all parts of the uterus,and therefore early conception after pregnancy tends to result in abnormal im-plantation sites; once pregnancy changes have resolved, the major blood supply

to the uterus is at the fundus, where implantation is optimal In communitieswhere breast-feeding is almost continuous throughout a woman’s life, the average interpregnancy interval is about 2 years Unfortunately, the absence ofmenstruation associated with breast-feeding is not a guarantee that ovulationhas not occurred, because a menstrual period happens only after release of anovum that is not fertilized or that does not implant successfully Therefore, thefirst sign a woman may have that she has conceived again can be the swelling ofher abdomen, or morning sickness Thus, lactation is not a reliable contracep-tive method However, together with a barrier method of contraception, or theprogestogen-only pill (see later) the failure rate is probably acceptable unlessanother pregnancy is completely contraindicated

very widely used Claims have been made for ‘method failures’ of less than0.1/100 woman-years, but everyday clinical experience is that the overall fail-ure rate is of the order of 1–5/100 woman-years The combined pill works

by suppressing ovulation Most of the pregnancies are probably the result of

‘patient failures’, with the woman forgetting to take her pill A missed pill is unlikely to result in conception during most of the pill-taking cycle, but ovariansuppression is at its lowest during the pill-free week, during which endometrialwithdrawal bleeding occurs (usually interpreted by the woman as a ‘period’),and thus missed pills just before or just after the pill-free week have the highestrisk of allowing an unwanted conception Some failures may be the result ofgastrointestinal upsets with intestinal hurry and decreased absorption, and co-incident administration of drugs such as rifampicin, phenytoin, phenobarbital,phenylbutazone and antibiotics, which speed metabolism or reduce absorption

of the synthetic sex hormones Women with heart disease are a well-motivatedgroup, who generally read the instructions or are well instructed, and their fail-ures with the pill should be at the lower end of the range Recovery of fertilityafter ceasing to take an oral contraceptive is a bit slower than after other meth-ods of contraception, but 80% of previously fertile women have had a babywithin 18 months and 95% within 3 years

Risks of oral contraceptives in patients with heart disease

The main concern is the risk of thromboembolic problems, including pulmonary embolism, biochemical changes predisposing to deterioration ofatherosclerosis, hypertension, myocardial infarction in older women and he-modynamic changes consequent on fluid and electrolyte retention These haz-ards have perhaps been overestimated in the past, because of overemphasis onisolated cases and the fact that when they were first introduced the amounts ofsynthetic sex hormones in contraceptive pills were substantially higher thanthey are today Moreover, the content of combined pills has evolved and threegenerations of progestogens have been introduced, for example

Thrombosis and embolism

The propensity of estrogen to increase the risk of venous thromboembolism hasbeen appreciated since the first report of this effect in 1961 This resulted in aprogressive decrease in the dose of estrogen used, so that currently most employ

a dose of 30μg or even less However, multiple studies in the 1990s have shownthat even this low dose is associated with a three- to sixfold increased relativerisk of venous thromboembolism.2The risk is highest during the first year ofuse, but persists even with prolonged use However, because the baseline risk ofvenous thromboembolism (VTE) is low in young healthy women (estimated as

1 VTE/10 000 women per year), the absolute risk remains low (3–6 VTE/10 000women per year using oral contraception) These figures relate to combinedoral contraceptives using norethisterone (first-generation progestogen) or lev-onorgestrel (second-generation progestogen) Third-generation progestogenssuch as gestodene and desogestrel, introduced because of their more favorable

effect on metabolic profiles, have since been shown to double the risk of the VTEfurther and formulations using them are therefore particularly unsuitable forwomen at risk of VTE.3,4All these risks are substantially increased in womenwith thrombophilias such as factor V Leiden or protein C deficiency Other riskfactors include maternal obesity.

Provided that women with either a personal or family history of VTE are cluded, the risk of either a thrombosis or an embolism in the average womantaking a modern estrogen–progestogen oral contraceptive is low, of the order of

ex-1 in 3300/year, even though it is three times higher than in women not takingthese preparations On the other hand, the comparable risk of thrombosis orembolism in a pregnancy that the contraceptive would have prevented is 10 per

10 000 pregnancies, twice as high as in women taking a contraceptive pill Thus,the risk of VTE is probably acceptable when the need to avoid pregnancy is ashigh as it is in women with significant heart disease Nevertheless, these issuesmust be brought to the patient’s notice and ultimately the choice must be left

to her

The position with patients taking oral anticoagulants remains unclear On theone hand, they are protected against the risk of thrombosis, but, on the other,they are by definition a high-risk group If a patient on prophylactic anticoagu-lants strongly desires oral contraception and has a strong case for really effectivecontraception, such as previous failures with other procedures, then the un-known nature of the risk must be explained before acceding to her wishes.Many doctors would deny oral contraceptives to a patient on full anticoagula-tion for an artificial heart valve, but information to support such a stance is notavailable

Biochemical changes and atherosclerosis

In the past, the balance of evidence was that the estrogen components of a bined pill tended to increase high-density lipoprotein (HDL)-cholesterol, whichshould reduce the risk of atherosclerosis, whereas progestogens appear to lowerHDL-cholesterol and counterbalance the estrogen effect Some progestogensalso raise low-density lipoprotein (LDL)-cholesterol, which might have a dele-terious effect However, overall the general effect on cardiovascular risk wasthought either to be neutral5or possibly even positive The perception of neu-trality has been supported by the Women’s Health Initiative trial of hormone re-placement therapy,6which reported a hazard risk for breast cancer of 1.26, forstroke 1.41 and no effect overall on the risk of cardiovascular disease If a patientconsidered to be at risk for atherosclerosis requests oral contraception, it maywell be prudent to estimate plasma lipids before starting the combined oral con-traceptive pill If the levels are normal, the risk is unlikely to be substantial;however, probably the estimation of plasma lipids should be repeated after 2months of taking the pill and every 3 months thereafter

com-Hypertension

The combined oral contraceptives can cause hypertension in a small number ofnormotensive women, but with careful monitoring of blood pressure (BP) this

is not a major prospective contraindication to their use However, there is someevidence that the combined oral contraceptive is contraindicated in womenwho are already hypertensive, and should be discontinued if hypertension isdetected.7

It is therefore wise to be cautious in this respect in women with heart disease.Those who are normotensive and wish to take an oral contraceptive shouldhave their BP checked 1 month after starting, again at 2 months and thereafterwhen the prescription is renewed Women with heart disease who are alreadyhypertensive are best advised of the risk, albeit small, of their hypertension deteriorating If they feel that their reasons for taking an oral contraceptive outweigh this risk, then monthly checks on BP are desirable

Myocardial infarction

Soon after oral contraceptives were first marketed in the 1960s, case reportslinked their use to the occurrence of myocardial infarction Over the past fewdecades, numerous studies have examined the cardiovascular complicationsassociated with oral contraceptive use, and have reached conflicting conclu-sions However, a recent meta-analysis of 19 case–control studies and four co-hort studies8has found that current users of the oral contraceptive pill have anoverall adjusted odds ratio of myocardial infarction of 2.48 compared withnever users Use of the oral contraceptive pill interacted with other risk factorssuch as smoking, hypertension, hypercholesterolemia and mutation in the pro-thrombin gene, resulting in odds ratios as high as 9 Interestingly, the overallodds ratio for past users was not significantly different from never users, being1.15 (with confidence interval, CI = 0.98−1.35) As a result, women with pre-disposing factors for ischemic heart disease should be strongly advised not totake the combined estrogen–progestogen oral contraceptive pill Patientsknown to have coronary artery disease should be told that these preparationsare absolutely contraindicated

Use of the oral contraceptive pill in

other cardiac conditions

The World Health Organization (WHO) has classified contraindications intofour grades, the first being no contraindication, the second where the advan-tages of the method generally outweigh the theoretical or proven risks, the thirdwhere the theoretical or proven risks usually outweigh the advantages (so thatanother method would be preferable, but a woman may still choose the method for personal reasons), and the fourth an unacceptable health risk Table23.2 indicates the varieties of heart disease in the various categories of contraindication

Progestogen-only oral contraceptives

Not only do these contraceptives not contain estrogen, the dose of progestogen

is also much lower than in the combined pill They do not usually prevent

Table 23.2 Cardiac contraindications to use of the combined oral contraceptive pill

WHO grade 2 (advantages WHO grade 3 (risks WHO grade 4

outweigh risks) outweigh advantages) (contraindicated)

Dysrhythmias other Atrial fibrillation or flutter

than atrial fibrillation

or flutter

Uncomplicated valve Pulmonary hypertension or

lesions including pulmonary vascular disease

mitral and bicuspid Pulmonary arteriovenous

aortic valve prolapse malformation

Prosthetic or tissue Bileaflet mechanical valve in Björk–Shiley or Starr–Edwards

heart valves mitral or aortic position on valves, even on warfarin

warfarin Fully surgically corrected Heart disease or thrombosis Poor left ventricular function

congenital heart disease well controlled on warfarin (left ventricle ejection

with careful supervision of fraction <30%) INR

Non-reversible trivial All known interatrial Dilated left atrium ( >4cm)

left-to-right shunts, communications – risk of Cyanotic heart disease

e.g small VSD or trivial paradoxical embolism

patent ductus arteriosus

Repaired coarctation Repaired coarctation with

without aneurysm or aneurysm or hypertension

hypertension

Uncomplicated Marfan Marfan syndrome with

syndrome aortic dilatation, unoperated

Uncomplicated pulmonary Post-surgery Fontan heart,

Hypertrophic obstructive Dilated cardiomyopathy or

pregnancy related or with residual left ventricular

other cardiomyopathy, dysfunction

fully recovered with

normal heart on Any past venous or arterial

echocardiography thromboembolic event,

not on warfarin INR, international normalized ratio; IUCD, intrauterine contraceptive device; VSD, ventricular

septal defect; WHO, World Health Organization.

After Guillebaud 9

ovulation, but rely on preventing the midcycle increases in cervical mucus meability, thus preventing sperm penetration into the female genital tract Asthey do not prevent ovulation, they are less reliable than combined estrogen–progestogen preparations, with failure rates of 2–5/100 woman-years, andmissing a single pill can result in pregnancy For this reason, they require a highdegree of patient motivation and are not suitable for women who find it difficult

per-to remember per-to take the pill every day Problems with irregular bleeding andepisodes of amenorrhea, leading to suspicions of pregnancy, are common As aresult, discontinuation rates with the method are high — many women request

an alternative after 1–2 years As a result of their relatively high failure rate, theyare not suitable for women at very high cardiac risk, for whom a pregnancywould be disastrous, e.g in women with significant pulmonary hypertension.The main reason for the promotion of the progesterone-only pill has been theassumption that, because there is no estrogen, and the progestogen dose is low,the effects on thrombosis and the cardiovascular system must be much less thanwith the combined pill Unfortunately, there is a paucity of well-conducted stud-ies, and the data sheet, even for norethisterone, which has been in use for over

40 years, says that it is contraindicated in women with previous bolism However, there is no evidence to support this assertion and papers arenow appearing that support the view that thrombosis is unlikely to be a serious risk with the progesterone-only pill.2,10Moreover, a recent review ofpublished literature suggests that the progesterone-only pill does not induce hypertension and is probably not contraindicated in women with hyperten-sion.11Nor is there any significant evidence of metabolic disturbance with theiruse For these reasons, many authorities (including Guillebaud9) suggest thatthe progesterone-only pill is suitable for motivated women with structural heartdisease who can cope with some irregularity in their menstrual pattern

thromboem-Contraception postpartum may be particularly important to the cardiac tient, who may wish to postpone or prevent another pregnancy In about 20%

pa-of women, the combined oral contraceptive pill will reduce breast milk tion, which appears to be unaffected using the progestogen-only oral contra-ceptive As lactational amenorrhea is quite an effective contraceptive on itsown, there seems to be a logic in combining the two However, it must be emphasized that the body of literature supporting the use of the progesterone-only pill is much smaller than that for the combined preparation

produc-Recently, a new progestogen-only pill (Cerazette) has been introduced taining 75μg desogestrel This does suppress ovulation, and therefore has a fail-ure rate similar to that of the combined oral contraceptive pill Moreover, theincreased effectiveness prolongs its efficacy if the woman forgets to take her pill,

con-so increasing the time that the woman can remember to take her pill and restorecontraceptive efficacy, up to 12 hours after the missed dose This improved effi-cacy makes it more suitable for women with high-risk cardiac lesions Cerazette

is metabolized after ingestion into etonorgestrel, which is used in the gen implant system Implanon It can therefore be used to test a woman’s toler-ance of this hormone before the implant is inserted surgically

progesto-Other forms of progestogen contraception

Vaginal rings

Vaginal rings releasing a progestogen (desogestrel) are already available in theUSA and in some European countries They have proved very popular in stud-ies, with excellent cycle control and very few contraceptive failures The ring isremoved for 1 week out of 4, to allow a withdrawal bleed It is too early to saywhether they will be suitable for women with heart disease

Injectable depot progestogens

Injectable progestogens, such as depot medroxyprogesterone acetate, are onesolution to poor patient compliance, because they are administered by a nurse

or similar professional, and relieve the patient of the responsibility for bering to take pills Medroxyprogesterone injections need to be given only onceevery 12 weeks to be effective They have been repeatedly endorsed by theWHO and the International Planned Parenthood Federation, and are currentlyavailable for long-term contraceptive use in more than 130 countries Despitethis, they are used by fewer than 2% of women in the UK, because of concernsfrom women and professionals about the irregular uterine bleeding that theycan provoke, especially when being discontinued Nevertheless, women whofind it difficult to take pills regularly may find it a preferable alternative to IUCDs

remem-or sterilization The cardiovascular contraindications are essentially the same asfor the progesterone-only pill

Implants

One of the early subcutaneous progestogen implants to be introduced, plant, turned out to be difficult to remove, resulting in legal action from somewomen This naturally had an adverse effect on public and professional confi-dence However, more recently, Implanon has been introduced successfullyinto the UK It is a single 40 mm long tube, 2 mm in diameter, and is far easier toinsert than Norplant It contains etonorgestrel A major advantage is an ex-tremely low failure rate, with current reports of less than one failure per 1000insertions.12It is inserted into the upper non-dominant arm under local anes-thetic; training in insertion is necessary Removal is easy but also needs training.The risks associated with its use are likely to be similar to those with the otherprogestogens Twenty percent of women become amenorrheic with its use, butmany women develop irregular periods instead, and this is the most commonreason why its removal is requested It currently needs to be removed and re-placed every 3 years

Nor-Emergency contraception

The ‘morning-after’ pill

The ‘morning-after ’pill is intended to prevent implantation if taken within 3days of unprotected intercourse The most widely used regimen consists of a

total of 100 μg ethinylestradiol and 500μg levonorgestrel repeated after

12 hours It is unwise to give a cardiac patient such a large dose of estrogen even for a short time, and systemic upsets — nausea, vomiting, headaches anddizziness — are common A single dose (1.5 mg) of levonorgestrel (Levonelle) ismore effective (1% pregnancy rate if used within 72 hours), has fewer side effects and is less prothrombotic, but it interacts with warfarin, increasing theinternational normalized ratio (INR) up to four times However, insertion of

an IUCD is effective even up to 5 days after unprotected intercourse, and this is probably the preferred alternative in women who need on-going contraception

Intrauterine contraceptive devices

These devices have been described as the best available contraceptive for a portion of parous women at certain times in their reproductive lives They relieve the couple of taking day-to-day responsibility for contraception, apartfrom verifying the presence of the device monthly, after menstruation, by pal-pating the strings in the cervix Failure rates of modern copper-containingIUCDs are comparable with oral contraceptives The original ICUDs were madeentirely of plastic (e.g the Lippes loop) but they had an unacceptable failure rateand have been completely superseded by copper and progestogen-bearing devices Once inserted, they are licensed to be effective for 3 and 5 years respectively

pro-Complications of the insertion procedure

About 10% of women develop tachycardia during insertion of an IUCD, and2% will develop a bradycardia or develop a transient arrhythmia Vasovagalsyncope caused by dilatation of the cervix without analgesia or anesthesia canoccur during insertion of a device; this phenomenon has been witnessed personally by me However, it is rare; a recent review of 545 IUCD insertions reported only one case.13A cardiac patient should therefore be prepared for insertion of a device with a premedication including atropine, and insertionconducted under hospital conditions rather than in a family planning clinic In-sertion should be done by an experienced practitioner, with a skilled anesthetist

in attendance in case of complications Perforation of the uterus when a device

is inserted is rare, occurring in about 1 in 1000 insertions A copper-bearing vice that has perforated should be removed promptly to prevent bowel adhe-sions forming The implications for a patient with heart disease are those of thelaparoscopy or laparotomy that is likely to be necessary for removal A basic rulefor the prevention of perforation during insertion is to discontinue the attemptpromptly if the patient is not fully relaxed or experiences significant pain

de-The risk of infection

The vagina and cervix always contain micro-organisms The cervical glands andmucus plug present an anti-bacterial barrier to their ascent into the uterus.When they are introduced into the upper genital tract, some of these organismsare potentially pathogenic The hazard can be much reduced by antiseptic