Heart Disease in Pregnancy - part 8 pptx

Arte-rial samples should be taken with the patient sitting up if possible.25,33 The electrocardiogram The ECG Table 17.4 may reveal evidence of right ventricular overload with clockwise

Physical signs are often deceptively few Clinical signs of acute right lar failure can be subtle Tachypnea is the most frequent followed by tachycar-dia The jugular venous pressure may be raised and there may be increased leftparasternal pulsation, a third heart sound gallop and widely split second sound.The lungs are usually clear but there may be focal crackles as surfactant is lostfrom non-perfused segments of lung At this stage the arrival of further emboliwill very probably be fatal, but otherwise the evidence of acute cor pulmonalehas usually resolved in just a day or two.

strik-A low PCO2may be coupled with a low PO2sometimes contributed to by tral right-to-left shunting if the foramen ovale is patent This can lead to con-comitant stroke, which may dominate the clinical scene The association ofhypoxemia with hypocapnia and a respiratory alkalosis is always highly sugges-tive of pulmonary embolism but hypoxemia is not invariable.24,25

cen-Recurrent PE

Patients with shortness of breath and features of pulmonary hypertension mayhave had recurrent episodes of PE or give no such history but show widespreadperfusion defects on scanning

An underlying thrombophilia is likely but sometimes tests reveal toimmune disease with lupus or Behçet syndrome, and the pulmonary

au-hypertension has resulted from pulmonary arteritis with thrombosis in situ

rather than embolism In rare cases pulmonary angiography or cardiac netic resonance imaging (CMRI) may show multiple pulmonary artery branchstenoses

mag-Paradoxical embolism

Elevation of right atrial pressure favors paradoxical passage of emboli if theforamen ovale is patent A devastating stroke or unexplained systemic em-bolism should lead to a search for a cardiac source and suspicion of paradoxicalembolism, so concomitant PE and occult DVT should also be sought.26,27

Echocardiography with injection of a sonicated indicator while the patientperforms a Valsalva maneuver will force a right-to-left shunt, with passage ofbubbles through the defect and their appearance in the left atrium The tech-nique is more sensitive if imaging is performed from the transesophageal ap-proach If patency of the foramen ovale is revealed after systemic embolism,device closure should be performed

Non-thrombotic PE

Amniotic fluid, fat, tumor or air may embolize to the lungs.28,29Fat embolismmay occur after major fractures Progressive pulmonary hypertension may re-sult from multiple microtumor embolism in chorioncarcinoma This sometimesdevelops years after a normal pregnancy or abortion A pregnancy test should

be performed if there is clinical suspicion Air embolism is a complication of tral venous lines and special care is necessary when the right atrial pressure israised, in case of patency of the foramen ovale A much smaller amount of airthan is tolerated on the right side can have devastating consequences when re-leased into the systemic circulation

cen-Embolism of amniotic fluid is usually asymptomatic and is common tum but, rarely, it causes sudden collapse during or after delivery, particularlyafter surgical delivery in multiparous patients but is distinguished by the dis-seminated vascular coagulopathy that usually follows

peripar-Diagnostic strategy

The diagnostic strategy depends on the initial hemodynamic presentation.30–32

Suspected PE always requires urgent confirmation or exclusion

In patients whose general condition is good and who are hemodynamicallystable there is time for diagnostic imaging Suspicion rests on clinical prob-ability (see Figure 17.2) and diagnosis will follow the results of the baseline testsand scans (Figure 17.3)

Diagnostic delay must be minimized in patients needing urgent reperfusion(Figure 17.4) There is no time for imaging tests apart from immediate on-siteechocardiography Patients who are in cardiogenic shock need reperfusiontreatment right away Echocardiography also plays a central role in identifyingthose patients without shock but whose hemodynamic instability and pooreroutlook are shown by right ventricular dilatation

Baseline tests

Blood gases, ECG and chest radiograph are basic They may be uninformativediagnostically if they are all normal but they say much about the general condi-tion of the patient and are useful in exclusion of other conditions

Arterial blood gases

These are helpful but not specific and may be normal A normal alveolar–

arterial oxygen gradient does not exclude PE but a reduced PO2in an apparently

fit patient is highly significant, especially when combined with a low PCO2

Arte-rial samples should be taken with the patient sitting up if possible.25,33

The electrocardiogram

The ECG (Table 17.4) may reveal evidence of right ventricular overload with

clockwise rotation and right-sided T-wave inversion, low voltage, right axis and

rSr in V1 or occasionally right bundle-branch block.24

The chest radiograph

This is usually normal but a near-normal film in the setting of severe

respira-tory and circularespira-tory compromise is highly suggestive of massive PE The chest

radiograph is useful in ruling out other lung pathology such as pneumonia or

pneumothorax It may show non-specific abnormality such as patchy basal

at-electasis or pleural effusion or, rarely, one of the classic signs, a wedge-shaped

Figure 17.3 Diagnostic strategy for pulmonary embolism (PE) in stable patients CT,

computed tomography; CUS, compression ultrasonography a Reliability in pregnancy

needs further confirmation.

opacity caused by segmental infarction or focal oligemia (Westermark’s sign),indicating massive central embolic occlusion.24

D-dimers

These are breakdown products of fibrin clot They indicate on-going lysis A normal level is a rapid test, currently much used to rule out throm-boembolism but pregnancy itself increases the plasma D-dimer concentrationabove the normal upper limit of 500 ng/mL

fibrino-Normal ranges at different stages of pregnancy were recently establishedfrom quantitative assays in 50 normal pregnant women using a US Food andDrug Agency (FDA)-approved ELISA (enzyme-linked immunosorbent assay)method D-dimer levels increased through pregnancy and exceeded 500 ng/mL

in 50%, 75% and 100% of women in the three trimesters The study indicatedthat levels above 700, 1000 and 1420 have >50% likelihood of being abnormal

Short axis projections

DiastoleSystole

Figure 17.4 Transthoracic echocardiogram, short-axis projection, systole on the left, diastole on the right, showing diastolic bowing of the ventricular septum toward the left ventricle and reduced left ventricular volume in acute pulmonary embolism.

Table 17.4 The ECG in pulmonary embolism

T-wave inversion in leads III, aVF and right-sided chest leads

Right axis and clockwise rotation, dominant S–V5

rSr in V1; complete right bundle-branch block (rare)

Low voltage in limb leads

Qs in leads III and aVF

for each trimester (see Figure 17.3) but more studies are still needed beforethese figures can be relied on

Raised D-dimer levels are not specific but normal levels can be used to back upclinical assessment of the low probability to rule out PE and remove the need forimaging Levels raised above the recently established norms in otherwisehealthy pregnant women are highly suggestive of PE,34,35but more studies arestill needed

Diagnostic imaging (Table 17.5)

Echocardiography

Echocardiography is under-used as the most rapid diagnostic measure in gency circumstances.36It is also non-invasive and does not involve radiation.Right ventricular dysfunction is found in about a third of all patients with acute

emer-PE (see Figure 17.4) The degree of dilatation and severity of systolic tion give both therapeutic and prognostic guidance and are the single most im-portant prognostic factor for in-hospital death.37They are usually immediatelyavailable in the accident and emergency department (A&E) to A&E staff, cardi-ologists or obstetricians faced with a patient in shock or with recent onset of

dysfunc-Table 17.5 Diagnostic imaging in suspected pulmonary embolism

No lung scan needed if leg scan positive

Chest radiograph Usually normal or non-specific

Echocardiography Immediate availability

Shows RV (TTE), main PA branches (TOE) Perfusion scan Positive scan with normal chest radiograph; start heparin

Useful if SCT negative and clinical probability high Ventilation scan Useful if both radiograph and perfusion scan are abnormal

If abnormal consider antibiotics

If normal start heparin or both Spiral CT scan Positive scan with normal chest radiograph; start heparin

Useful if perfusion is equivocal and chest radiograph or ventilation are normal

May miss subsegmental PE CMRI Becoming more generally available; shows RV too

Pulmonary angiography Essential for fragmentation or embolectomy

Gold standard but invasive Involves radiation CMRI, cardiac magnetic resonance imaging; PA, pulmonary artery; PE, pulmonary embolism; RV, right ventricle; SCT, spiral computed tomography; TOE, transesophageal echocardiography; TTE, transthoracic echocardiography.

puzzling symptoms, and their usefulness will increase further as hand-held machines come into more general use

Although detection of right ventricular dysfunction lacks specificity, this is ofmuch less importance in the largely healthy pregnant population than in theolder suspect population with a higher incidence of co-morbidity Rarely,echocardiography will reveal a clinically unsuspected cardiomyopathy, parti-cularly peripartum cardiomyopathy with its high incidence of intraventricularthrombi that may present with pulmonary (or systemic) embolism

Otherwise unexplained right ventricular dilatation, poor function and pid regurgitation are frequently a surprise in patients with negative clinicalfindings who may have complained only of some shortness of breath, transientdizziness or faintness, and who do not appear to be in distress Bowing of theventricular septum towards the left ventricle in diastole indicates right ventric-ular volume overload.38,39Rarely, worm-like emboli swim in the right atrium topoke in and out of the tricuspid valve or extend into the ventricle or pulmonaryartery.40The central pulmonary arteries are not seen in transthoracic views forwhich transesophageal imaging is needed

tricus-Transesophageal echocardiography does not have the brilliant immediacy oftransthoracic echocardiography but needs no preparation or cooperation fromradiological colleagues to delay it It shows the main pulmonary artery, the rightand the proximal left pulmonary artery, and any thrombi or filling defects.41

Compression venous Doppler ultrasonography

Loss of venous compressibility indicates thrombosis Augmentation of flow isabsent or reduced during compression This is the primary diagnostic test forDVT because it is non-invasive and totally safe for the fetus The test is highlysensitive and specific for proximal DVT with thrombosis of femoral veins, but

is not reliable for isolated iliac thrombosis (more prevalent during nancy) and ultrasound diagnosis of isolated calf vein thrombosis needs specialexpertise.13,42

preg-About half of all patients with PE have no imaging evidence of DVT Although

a normal ultrasound examination therefore does not rule it out, its tion indirectly establishes the diagnosis of PE but false-positive results may beobtained in the third trimester as a result of compression of the iliofemoral veins

identifica-by the uterus

Real-time ultrasonography

The common femoral vein and popliteal vein can be visualized and intraluminalclots detected, although their echogenicity varies according to their age Real-time imaging uses standard equipment, is easy, and can be repeated and com-bined with compression It cannot detect isolated iliac vein thrombosis

Contrast phlebography

This is reserved for investigation of equivocal results of ultrasound examination

in patients with high clinical probability of DVT but with no evidence of PE It is

rarely indicated in pregnancy but the alternative may possibly be unnecessaryheparin treatment.

Ventilation–perfusion scans

Perfusion lung scans

These are indicated as the primary test for PE They are performed by injectingtechnetium-99m (99mTc) coupled to microaggregates of human albumin andscanning the distribution of radioactivity with a gamma camera The radiationdose to the fetus is minimal A normal scan rules out PE Unfortunately an ab-normal scan cannot confirm the diagnosis, although non-specific abnormalitiesare less frequent in pregnant patients than in an older age group Large perfu-sion defects with a normal chest radiograph are likely to be the result of PE andmake a ventilation scan unnecessary The original classification stemming fromthe PIOPED trial has been revised44and was followed by the attempt in the PISAPED trial with the aim of eliminating equivocal results.45

Ventilation scans

These employ inhaled xenon-133 (133Xe) or krypton-81m (81mKr) An mal perfusion scan followed by a normal ventilation scan is diagnostic of PE andreported as ‘high probability of PE’ Matched abnormalities in perfusion andventilation scans with an abnormal chest radiograph are likely to be caused byinfection One reason for abnormalities on the ventilation scan, especiallywhen a scan is delayed, is the patchy atelectasis of embolized segments of lungthat often follows in the next few days The radiation dose is similar to that with

abnor-a perfusion scabnor-an

Doubt has been expressed as to whether the ventilation scan is any more ful than a chest radiograph in interpreting the perfusion scan

use-Spiral computed tomography

With the development of more accurate scanners, spiral CT has increased inpopularity as the primary imaging test for PE.46,47This preference is becauseventilation–perfusion scans still produce so many equivocal results in older pa-tients with co-morbidity, among whom reports of ‘intermediate risk of PE’ arefrequent and frustrating They are especially likely when the chest radiograph isabnormal These limitations of ventilation–perfusion scans are much less of aproblem in the younger and otherwise healthy pregnant population

Spiral CT produces a definite positive or negative result but is less accurate inrevealing segmental PE than central or lobar emboli A normal study thereforecannot rule out isolated peripheral subsegmental PE or be the basis for with-holding anticoagulant treatment

The technique has the disadvantages of both exposure to radiation and a fetaldose of iodinated contrast, although the fetal radiation dose with spiral CT islower than with ventilation–perfusion scanning and neonatal hypothyroidismhas not been reported

Magnetic resonance imaging

MRI with gadolinium enhancement now has similar accuracy to pulmonaryangiography and CMRI also allows assessment of ventricular function It avoidsradiation and the use of radiographic contrast and imposes no risk, but is notusually immediately, or as yet generally, available.48

Both spiral CT and MRI can be extended to look for DVT but there is no point

if imaging for PE has been positive Neither CT nor MRI are needed if leg vein ultrasonography is positive

Management

Patients in cardiogenic shock or hemodynamically unstable

Massive and subacute massive PE

The management of a patient with a high clinical probability of PE and who is inshock is aimed at restoring circulation and saving life (Table 17.6) The diagnosisneeds to be confirmed and action taken with no time lost (Figure 17.5) If the di-agnosis is confirmed by right ventricular dilatation shown on transthoracicechocardiography, percutaneous catheter fragmentation and thrombolysis(Figure 17.6) should be carried out immediately and without delay for other investigations.18,31,52–54It is usually successful if the embolism was truly acute It

Table 17.6 Massive pulmonary embolism (emergency treatment to save life)

Cardiopulmonary resuscitation (CPR) if circulatory arrest

Elevate legs

Oxygen

Central intravenous line

Start heparin

Consider dobutamine infusion

Consider inhaled nitric oxide

Thrombolytic drug

Per catheter clot fragmentation and/or extraction

will fail if the circulation has collapsed after apparent sudden onset, although all

or most of the material has been gradually accreted through recurrent episodes

A pigtail catheter should be introduced by the brachial route or central veinwith the patient tilted head down Fragmentation can be accomplished veryswiftly and, if it is successful, blood pressure and consciousness are restoredwithin minutes The extreme emergency is over The catheter is inserted via abrachial or central route so as to avoid dislodging any thrombus in the pelvis orvena cava, and to save the fetus from radiation if the patient is undelivered Pro-vided that the obstruction is caused by freshly arrived embolic material that isstill lying centrally, it can usually be moved on with dramatic improvement.Formal angiography is not required but contrast is needed to guide the proce-dure and should be used as sparingly as possible

If attempts to fragment central emboli and move them on are cessful, per catheter embolectomy should be tried and, if all else fails, surgicalembolectomy

Cardiogenic shock

Echocardiography

Dilated RV Dilated RV

Central Spiral CT

Unsuccessful

Figure 17.5 Management strategy in patients with pulmonary embolism (PE) again stressing the key role played by echocardiography RV, right ventricle a Reliability in pregnancy needs further confirmation.

Other measures are adjuvant The legs should be elevated and oxygen given.

If consciousness has been lost chest compression will help to empty the rightventricle and be directly therapeutic if it dislodges thrombi and assists in movingthem on If the circulation is compromised and the right ventricle dilated, butthe patient is conscious and not in shock, there is time for perfusion or spiral CT

to assess the size and distribution of the clot burden

A central line is inserted and unfractionated heparin is started It is usual togive inotropes and vasopressors but, unless an effective circulation returns rap-idly, an attempt should be made to fragment the emboli per catheter Dobuta-mine is usually given even though endogenous neuroendocrine activation islikely to be providing maximum stimulation already Dobutamine providespositive inotropic effect with pulmonary vasodilatation through its beta-adrenergic action Inhaled nitric oxide may release pulmonary vasoconstrictionand help to reduce right ventricular afterload

Fluid loading is probably unhelpful and no more than 500 mL fluid should begiven, more only if it appears to have been beneficial (as ventricular interdepend-ence may cause further compromise of left ventricular filling) This can most rap-idly be appreciated by following the effect of the infusion echocardiographically Thrombolytic treatment with recombinant plasminogen activator (rtPA)should be given only if the circulation remains compromised This does not

Figure 17.6 The right digital subtraction pulmonary arteriogram from a patient with massive pulmonary embolism (a) before and (b) after restoration of flow to the lower lobe by mechanical fragmentation The pigtail catheter is clearly visible.

cross the placenta or directly injure the fetus but may cause bleeding and fetalrisk It can be started immediately after completion of mechanical fragmenta-tion and given directly into the pulmonary arteries (although there is no proof

of added efficacy by this route) Infusion of unfractionated heparin should follow

Clinically stable patients

If the patient is hemodynamically stable with maintained blood pressure andcardiac output, anticoagulant treatment with heparin may be all that is requiredplus oxygen and pain relief Absence of right ventricular dilatation on echocar-diography adds reassurance but the risk of recurrent embolism continues untilexisting venous thrombus has been autolysed or organized Now is the time forinsertion of a prophylactic caval filter18if this is contemplated but the pro-cedure, although improved, involves radiation, carries morbidity and is not always successful in preventing recurrence

Patients who have suffered PE are at risk from recurrence until any thrombus

in leg and pelvic veins has lysed, embolized or organized Thrombolytic agents

do not work immediately or completely, but patients who are destined to vive sometimes improve before thrombolytic activity has started through on-ward movement, compaction or shrinkage of embolized material Heparin is

sur-not lytic and resorption of non-embolized material depends on endogenouslysis which is very active in the lungs Patients who have suffered massive ormajor embolism are probably less likely to harbor unstable peripheral thrombusthan patients suffering minor embolism, but are in a worse position to sustainanother onslaught until resolution of the first Further embolism from legs orpelvis remains a risk for the first few days and weeks

Prevention of PE

Diagnosis of venous thrombosis

A full history is important because a positive history indicates the need to form a full coagulation screen and to institute prophylactic measures in anyonewith a personal or family history of unexplained thrombosis This must be donebefore anticoagulants are started Physical methods of prophylaxis include pos-ture (sleeping semi-prone rather than supine in later pregnancy) and compres-sion stockings LMWH should be given to high-risk patients

per-Prevention of PE relies on the prevention, rapid diagnosis and effective ment of venous thrombosis Accurate objective diagnosis is important because

treat-of the mortal risk from PE if DVT is untreated and also because long-term coagulant treatment in pregnancy carries risk to both mother and fetus, and apositive diagnosis has implications for prophylaxis in future pregnancies Accu-rate diagnosis is mandatory (Table 17.7)

anti-Clinical probability is assessed on medical history and clinical examination.Thrombosis is most frequent in the left femoral vein and calf antenatally Dis-tinction has to be made from benign pregnancy associated swelling, which isusually slowly progressive, painless and bilateral although occasionally rapidand unilateral even in the absence of thrombosis

Perspective

Although thromboembolism is frequently missed it is still rare compared withthe frequency with which it is suspected and the prevalence of high probabilityventilation–perfusion scans in pregnant women with suspected PE is very low

Table 17.7 Possible deep vein thrombosis (DVT)

High index of suspicion needed:

— half of patients with a PE do not have any sign of a DVT

— half of patients with an acutely swollen calf do not have a DVT

Investigation:

D-dimer: promising, needs more pregnancy data

— real-time venous ultrasonography: available, easy, non-invasive

— compression Doppler ultrasonography: needs expertise, non-invasive

— phlebography: invasive, involves radiation, painful, may cause DVT

Withholding anticoagulation in pregnant women with a low clinical ability of PE, negative leg Doppler and normal or non-diagnostic ventilation–perfusion scans is probably safe but simpler means of ruling out thromboem-bolism are needed The reliability of a negative pregnancy level D-dimer in ruling out thromboembolism without the need for further investigation ispromising but more data are awaited.

prob-References

1 Rutherford S, Montoro M, McGehee W, Strong T Thromboembolic disease

associated with pregnancy: an 11 year review Am J Obstet Gynecol 1991;164(suppl):

throm-based, case–control study Am J Obstet Gynecol 2001;184:104–10.

5 Toglia MR, Weg JG Venous thromboembolism during pregnancy N Engl J Med

1996;335:108–13.

6 Hirsch DR, Mikkola KM, Marks PW et al Pulmonary embolism and deep vein

throm-bosis during pregnancy or oral contraceptive use: prevalence of factor V Leiden Am

Heart J 1996;131:1145–8.

7 Peek MJ, Nelson RA, de Swiet M, Letsky EA Activated protein C resistance in normal

pregnancy Br J Obstet Gynaecol 1997;104:1084–6.

8 Bauer KA Hypercoagulability — a new co-factor in the protein C anticoagulant

path-way Lancet 1994;330:566–7.

9 Preston FE, Rosendaal FR, Walker ID et al Increased fetal loss in women with

herita-ble thrombophilia Lancet 1996;348:913–16.

10 Carr MH, Towers VC, Eastenson AR, Pircon RA, Iriye BK, Adashek JA Prolonged bed rest during pregnancy: does the risk of deep vein thrombosis warrant the use of rou-

tine heparin prophylaxis? J Matern Fetal Med 1997;6:264–7.

11 Weiner CP, Kwaan AC, Xu C et al Antithrombin III deficiency in women with

hyper-tension during pregnancy Obstet Gynecol 1985;65:301–6.

12 Lindqvist P, Dahlback B, Marsal K Thrombotic risk during pregnancy: a population

study Obstet Gynecol 1999;94:595–9.

13 Kyrle PA, Eichinger S Deep vein thrombosis Lancet 2005;365:1111–202.

14 Khamashta MA, Mackworth-Young C Antiphospholipid (Hughes’) syndrome — a

treatable cause of recurrent pregnancy loss BMJ 1997;314:244.

15 Den Heyer M, Koster T, Blom HJ et al Hyperhomocysteinaemias a risk factor for deep

vein thrombosis N Engl J Med 1996;334:759–62.

16 Rosendaal FR Risk factors for venous thrombosis disease Thromb Haemost

1999;82:610–19.

17 Prandoni P, Lensing AW, Coigo A et al The long term clinical course of acute deep

venous thrombosis Arch Intern Med 1996;125:1–7.

18 Task Force on Pulmonary Embolism, European Society of Cardiology Guidelines on

diagnosis and management of acute pulmonary embolism Eur Heart J 2000;21:

1301–36.

19 The PIOPED Investigators Value of the ventilation–perfusion scan in acute monary embolism Results of the prospective investigation of pulmonary embolism

pul-diagnosis JAMA 1990;263:2753–9.

20 Sergysels R Pulmonary gas exchange abnormalities in pulmonary embolism

In Morpurgo M (ed.), Pulmonary Embolism New York: Marcel Dekker, 1994:

pp 89–96.

21 Colman NC Pathophysiology of pulmonary embolism In Leclerk JR (ed.), Venous

Thromboembolic Disorders Philadelphia: Lea Febiger, 1991: pp 65–73.

22 Coon WW, Coller FA Clinicopathologic correlation in thromboembolism Surg

elec-existing cardiac or pulmonary disease Chest 1991;100:598–603.

25 Stein PD, Henry JW, Miller AC Arterial blood gas analysis in the assessment of

sus-pected acute pulmonary embolism Chest 1996;109:78–81.

26 Amarenco P Patent foramen ovale and the risk of stroke: smoking gun guilty by

asso-ciation? Heart 2005;91:441–7.

27 Konstantinides S, Geibel A, Kasper W, Olschewski M, Blumel L, Just H Patent men ovale is an important predictor of adverse outcome in patients with major pul-

fora-monary embolism Circulation 1998;97:1946–51.

28 Gei AF, Vadhera RB, Hankins GD Embolism during pregnancy: thrombus, air and

amniotic fluid Anesthesiol Clin North Am 2003;21:16.

29 Berkowitz KD, Goldstein DP Gestational trophoblastic disease Cancer 1995;76:

2079–85.

30 Kearon C Diagnosis of pulmonary embolism Can Med Assoc J 2003;168:1–22.

31 Kucher N, Luder CM, Dornhofer T, Windecker S, Meier B, Hess OM Novel

manage-ment strategy for patients with suspected pulmonary embolism Eur Heart J 2003;24:

366–76.

32 Nijkeuter M, Geleijns J, de Roos A, Meinders AE, Huisman MV Diagnosing monary embolism in pregnancy: rationalising fetal radiation exposure in radiological

pul-procedures J Thromb Haemost 2004;2:1857–8.

33 Ang CK, Tan TH, Walters A, Wood C Postural influence on maternal capillary oxygen

and carbon dioxide tension BMJ 1969;4:201–3.

34 Hernandez J, Hambleton G, Kline JA D-dimer concentrations in normal pregnancy.

Acad Emerg Med 2004;11:526–7.

35 Morse M Establishing a normal range for D-dimer levels through pregnancy to aid in

the diagnosis of pulmonary embolism and deep vein thrombosis J Thromb Haemost

38 Mc Connell MV, Solomon SD, Rayan M, Come PC, Goldhaber RT Regional right tricular dysfunction detected by echocardiography in acute pulmonary embolism.

ven-Am J Cardiol 1996;78:469–73.

39 Kasper W, Geibel A, Tiede N et al Distinguishing between acute and subacute massive

pulmonary embolism by conventional and Doppler echocardiography Br Heart J

1993;70:352–6.

40 Chapoutot L, Nazerollas P, Metz D et al Floating right heart thrombi and pulmonary

embolism: diagnosis, outcome and therapeutic management Cardiology 1996;87:

169–74.

41 Pruszczyk P, Torbicki A, Pacho R et al Non-invasive diagnosis of suspected severe

pulmonary embolism: transoesophageal echocardiography vs spiral CT Chest 1997;

112:722–8.

42 Kearn C, Julian JA, Newman E, Ginsberg JS, for the McMaster Diagnostic Imaging

Practice Guidelines Initiative Non-invasive diagnosis of deep vein thrombosis Ann

Intern Med 1998;128:663–77.

43 Chan WS, Ray JG, Murray S, Coady GE, Coates G, Ginsberg JS Suspected pulmonary embolism in pregnancy: clinical presentation, result of lung scanning and subsequent

maternal and pediatric outcomes Arch Intern Med 2002;162:1170–5.

44 Sostman HD, Colman RE, DeLong DM, Newman GE, Paine S Evaluation of revised PIOPED criteria for ventricular perfusion scintigraphy in patients with suspected pul-

monary embolism Radiology 1994;193:103–7.

45 The PISA-PED Investigators Value of perfusion lung scan in the diagnosis of monary embolism: results of the prospective study of acute pulmonary embolism

pul-diagnosis (PISA-PED) Am J Respir Crit Care Med 1996;154:1387–93.

46 Doyle NM, Ramirez MM, Mastrobattista JM, Monga M, Wagner LK, Gardner MO

Diagnosis of pulmonary embolism: a cost-effectiveness analysis Am J Obstet Gynecol

2004;191:1019–23.

47 Mayo JR, Remy-Jardin M, Muller NL et al Pulmonary embolism: prospective

com-parison of spiral CT with ventilation/perfusion scintigraphy Radiology 1997;205:

447–52.

48 Goodman LR, Lipchik RJ, Kuzo RS et al Subsequent pulmonary embolism after a

negative pulmonary angiogram — prospective comparison with scintigraphy

Radio-logy 2000;215:535–42.

49 Johnson MS, Stine SB, Shah H, Harris VJ, Ambrosius WT, Trerotola SO Possible monary embolus: evaluation with digital subtraction versus cut-film angiography —

pul-prospective study in 80 patients Radiology 1998;207:131–8.

50 Oudkerk M, van Beek EJ, Wielopolski P et al Comparison of contrast enhanced netic resonance angiography and conventional pulmonary angiography for the diag-

mag-nosis of pulmonary embolism: a prospective study Lancet 2002;359:1643–7.

51 de Swiet M Management of pulmonary embolus in pregnancy Eur Heart J

1999;20:1378–85.

52 Brady AJB, Crake T, Oakley CM Percutaneous catheter fragmentation and distal

dis-persion of proximal pulmonary embolus Lancet 1991;338:1186–9.

53 Mazeika PK, Oakley CM Massive pulmonary embolism in pregnancy treated with

streptokinase and percutaneous catheter fragmentation Eur Heart J 1994;15:

C H A P T E R 1 8

Hypertensive disorders

of pregnancy

Alexander Heazell, Philip N Baker

Hypertensive disorders of pregnancy are the most common medical problemencountered in the second half of pregnancy, affecting about 6–10% of preg-nancies.1Although there are many different causes of hypertension in preg-nancy, the most clinically important condition is pre-eclampsia, affectingbetween 1 and 3% of pregnancies.2Pre-eclampsia is associated with increasedmaternal and fetal morbidity and mortality.3As there is no effective interven-tion for pre-eclampsia, except delivery, pre-eclampsia is responsible for about ahalf of induced pre-term deliveries, with the associated consequences of pre-mature birth

At present, the precise cause of pre-eclampsia is unknown, although it is derstood to be a disorder of widespread endothelial dysfunction It is hypothe-sized that decreased invasion and subsequent remodeling of maternal spiralarteries in the first trimester lead to reduced placental perfusion, and release

un-of factors into the maternal circulation, resulting in endothelial cell damage(Figure 18.1).4–6As every organ has a blood supply, pre-eclampsia should be regarded as a multi-system disease, which may affect each patient differently(Tables 18.1 and 18.2) Therefore, the management of pre-eclampsia involvesfar more than the treatment of hypertension alone

In normal pregnancy the maternal blood pressure decreases in the first half ofpregnancy, rising to pre-pregnancy levels or higher from about 30 weeks’ gesta-tion Hypertension in pregnancy is defined as a blood pressure >140/90mmHg

on two separate occasions, at least 4 hours apart, or a single diastolic reading

>110mmHg.7 If this occurs before 20 weeks’ gestation, it is presumed to

be chronic hypertension If new hypertension occurs after 20 weeks’ tion without proteinuria, it is termed ‘pregnancy-induced hypertension’.7

gesta-Pre-eclampsia is defined as new onset hypertension with proteinuria(>300mg/24h or ++ on urine dipstick) in the absence of a urinary tract infectionafter 20 weeks’ gestation.8If a patient with pre-existing hypertension developsproteinuria (>300mg/24h or ++), this is termed superimposed pre-eclampsia(Table 18.3) Eclampsia is defined as a tonic–clonic seizure occurring in the pres-ence of pre-eclampsia

Much of the antenatal care in the UK is directed towards the identification ofpre-eclampsia As there is currently no reliable screening test to identify women

264

Copyright © 2007 by Blackwell Publishing

who will go on to develop pre-eclampsia, regular screening of blood pressureand urine is carried out throughout pregnancy, because this has been shown toreduce perinatal mortality sevenfold In addition, women at risk of develop-ing hypertension in pregnancy should be identified The incidence of pre-eclampsia is increased in primigravidae (or first pregnancy with that partner),multiple pregnancies, women with a first-degree relative with hypertension inpregnancy, and at extremes of reproductive age.2,6,9,10Important risk factors in

a patient’s past medical history include: chronic renal disease, chronic tension (especially if poorly controlled), diabetes mellitus and thrombophil-

high-risk pregnancy, and managed in a specialist high-risk obstetric clinic, beingseen more frequently than ‘low-risk’ patients Patients who have had previouspre-eclampsia should also be managed as a high-risk pregnancy because the risk

of recurrence of some form of pre-eclampsia is between 20 and 40% depending

on the population studied.15

It is important to note that pre-eclampsia is a heterogeneous condition, andthe diagnosis may be made from the presence of clinical features, such as thoseabove, in combination with the presence of hypertension and proteinuria (seeTable 18.1) Patients may also have biochemical and/or hematological abnor-malities that may be found on further investigation (see Table 18.2)

Despite widespread abnormalities in the cardiovascular system, cardiologistsare rarely involved in the management of hypertensive disorders of pregnancy,except in severe or resistant hypertension or in other unusual circumstances,e.g secondary hypertension resulting from coarctation of the aorta Most cardiologists therefore have little experience in the routine management of

Abnormal trophoblast invasion

and failure of conversion of

Inappropriate activation of clotting cascade

Figure 18.1 Proposed pathophysiology of pre-eclampsia.

hypertension in pregnancy This may be a particular problem in pre-pregnancycounseling for women with hypertension, prophylaxis for pre-eclampsia, andthe use of pharmacological agents in pregnancy, or in the follow-up of patientswho have had pre-eclampsia Therefore, this chapter addresses hypertension inpregnancy with particular respect to these areas

Blood pressure measurement in pregnancy

The measurement of blood pressure in pregnancy is subject to the same lems as in normal patients, such as: selection of appropriate cuff size, observererror and bias, and blood pressure variability, all of which may affect the finaldocumented reading However, in pregnancy there are specific concerns relat-ing to the position of the patient The blood pressure is lower in the second half

prob-of pregnancy in patients lying supine This is because the gravid uterus obstructs

Table 18.1 Clinical features of pre-eclampsia

Central nervous system

Eclamptic convulsions

Cerebral hemorrhage, intraventricular or subarachnoid

Cerebral infarction: microinfarction or macroinfarction (e.g cortical blindness caused by infarction of occipital cortex)

Coagulation system

Thrombocytopenia

Microhemangiopathic hemolysis

HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)

Disseminated intravascular coagulation

Eyes

Retinal detachment

Retinal edema

Kidney

Acute tubular necrosis

Acute cortical necrosis

Unspecified renal failure