cardiac disease and hypertensive disorders in pregnancy · atinine >1.1 mg/dl, or doubling of...

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78Cardiac Disease and Hypertensive Disorders in PregnancyKenneth K. Chen, nihariKa Mehta, eriCa J. hardy, SrilaKShMi Mitta, and rayMond o. Powrie

HyPertensive DisorDers of PregnanCy

Hypertension during pregnancy has been classified by the American College of Obstetricians and Gynecologists into four distinct categories: (a) preeclampsia and eclampsia, (b) chronic hypertension (hypertension that was present before pregnancy), (c) chronic hypertension with superimposed pre-eclampsia or eclampsia, and (d) gestational hypertension (1). Most chronic hypertensive pregnant patients have essential hypertension, which has no appreciable effect during preg-nancy unless end-organ damage is present. Chronic hyperten-sion is seen in a critical care unit typically only when a patient has a hypertensive urgency/emergency unrelated to pregnancy, or if the patient has a secondary cause of hypertension that rep-resents a short-term risk to maternal health. Similarly, latent or transient hypertension is also relatively benign, occurring in the last trimester or the immediate postpartum period, with a return of normotension by the first 3 weeks after delivery. It is preeclampsia or eclampsia—whether occurring de novo or superimposed on pre-existing hypertension—that is most likely to require critical care support, and therefore will be the focus of this section.

Preeclampsia and Eclampsia

Preeclampsia is a multisystem disorder unique to human preg-nancies. Its pathophysiology is not well understood, and its cause is unknown. It is associated with an increased risk of fetal loss, intrauterine growth restriction, and preterm birth, and remains a leading cause of maternal death worldwide. Eclampsia refers to preeclampsia that is complicated by sei-zures, but it is our present understanding that the underlying condition is the same (2).

Although much of the care of the preeclamptic patient will fall into the domain of the obstetrician, familiarity with the manifestations and management of preeclampsia is important for any critical care physician. Primary obstetric disorders—of which, preeclampsia and its complications constitute the majority—account for 50% to 80% of ICU admissions during pregnancy and the puerperium in all parts of the world (3).

Risk Factors for Preeclampsia

Five percent to 8% of all pregnancies are complicated by pre-eclampsia, typically occurring in the final weeks prior to the due date and very rare prior to 20 weeks of gestation. The risk factors for preeclampsia are listed in Table 78.1. The diverse nature of the risk factors suggests that preeclampsia may be a common end point for a variety of processes related to placental dysfunction (4,5).

Etiology and Pathophysiology

Preeclampsia is believed to be an abnormal vascular response to the formation of the placenta. It is associated with endothelial cell dysfunction, activation of the coagulation sys-tem, enhanced platelet aggregation, and increased systemic vascular resistance. The maternal effects of these changes are manifest in the cardiovascular system, kidneys, lungs, and brain. Pathologic examination of affected maternal organs reveals areas of edema, endothelial swelling, microinfarc-tions, and microhemorrhages. The cardiovascular features of preeclampsia include decreased plasma volume—despite an increase in total-body water and salt retention—and colloid osmotic pressure, largely due to a drop in serum albumin (6). Generalized arteriolar vasospasm accounts for the hyperten-sion in preeclampsia, which is often very labile.

Our understanding of the etiology of preeclampsia is evolv-ing. The condition is felt to begin early in pregnancy, long before it becomes clinically apparent as the maternal syndrome. Three distinct, sequential phases occur in its evolution (4,7,8). The first phase is incomplete invasion of the trophoblast into the endometrium, perhaps due to a maladaptive immune response in the mother, followed by inadequate “placentation”— formation of the placenta—which leads to the second phase in which decreases in the levels of angiogenic growth factors and increased placental debris is found in the maternal cir-culation. This stage of the development of preeclampsia is not associated with any clinical symptoms or signs, however, decreases in placental growth factor (PlGF) and elevations of soluble FMS-like tyrosine kinase 1 (sFlt-1) and endoglin can be detected (9–11); these changes then incite a maternal inflam-matory response. The third phase is the response of the mater-nal endothelium and cardiovascular system to these stressors, which is modulated by the woman’s own level of metabolic and cardiovascular health and then leads to the clinical pre-sentation of the maternal preeclamptic syndrome. Although this response is manifested predominantly as hypertension and proteinuria, less common manifestations of cardiac, pulmo-nary, hematologic, neurologic, and hepatic complications can lead to admission in the intensive care unit.

Clinical Features

Clinically preeclampsia can have a highly variable presenta-tion. It can manifest as a fetal syndrome (abnormal fetal oxy-genation, reduced amniotic fluid, and fetal growth restriction), a maternal syndrome (proteinuria and hypertension with or without other multisystem abnormalities), or a combination of both. In most patients, both the fetal and maternal syn-drome will be apparent, however one or the other will often predominate in an individual case. This chapter will focus on the maternal manifestations.

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CHAPTER 78 Cardiac disease and hypertensive disorders in Pregnancy 907

Preeclampsia is defined by the maternal manifestations of hypertension and proteinuria occurring in the second half of pregnancy. The presentation and diagnostic features of pre-eclampsia are reviewed in Tables 78.2 and 78.3 (12–17). Although hypertension above 140/90 mmHg and proteinuria over 300 mg/24 hr are required for the diagnosis of preeclamp-sia, some cases may present initially without these features, or may present—as in the case of postpartum eclampsia—after some of these features have already resolved.

Preeclampsia is defined to be severe by the presence of one or more of the following (1):• Hypertension: systolic above 160 mmHg or diastolic above

110 mmHg on two occasions at least 4 hours apart while the patient is on bed rest

• Thrombocytopenia (platelet count <100,000 cells/µL)• Impaired liver function (elevated blood levels of liver trans-

aminases to twice the normal concentration)• Severe persistent right upper quadrant or epigastric pain

unresponsive to medication and not accounted for by alter-native diagnoses

• New development of renal insufficiency (elevated serum cre-atinine >1.1 mg/dL, or doubling of serum creatinine in the absence of other renal disease)

• Pulmonary edema• New-onset cerebral or visual disturbances

Eclampsia results when seizures occur that are not related to other underlying disorders. These features describe a group of patients with an increased risk of fetal and maternal morbidity for whom delivery should be strongly considered. Preeclamp-tic patients who lack any of the features of severe preeclampsia may have to be observed without moving toward delivery if the fetus is significantly premature and the mother remains under close observation; however, such patients are rarely seen in intensive care settings.

Life-threatening maternal complications of preeclampsia such as severe hypertension, seizure, cerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation (DIC), acute renal failure (ARF), and hepatic failure and/or

TablE 78.1 Risk Factors for Preeclampsia

Maternal•First pregnancy•new partners•age younger than 18 or older than 35 yr•Chronic hypertension•Prior history of preeclampsia•Family history of preeclampsia•Pregestational diabetes•obesity•thrombophilias•antiphospholipid antibody syndrome•Systemic lupus erythematosus•renal disease

Fetal•Multiple gestations•Molar pregnancies (can cause preeclampsia at <20 wk

gestation)•Fetal hydrops•triploidy

TablE 78.2 Clinical Features of Preeclampsia

Feature Description

Symptomsheadache the headache that characterizes preeclampsia is typically frontal in location, throbbing in character, persistent,

and not responsive to mild analgesia.

Visual phenomena the visual disturbances that characterize preeclampsia are presumed to be due to cerebral vasospasm and are typically scintillations or scotomas. longer-lasting visual field deficits and rarely transient blindness can result from edema, posterior reversible encephalopathic syndrome, and even infarction in the occipital region of the brain.

Serous retinal detachments can also occur in preeclampsia and are related to retinal edema. Magnesium, which is commonly used to prevent seizures in preeclamptic women, can cause mild visual blurring or double vision, but should not cause scotomas, scintillations, or visual loss.

epigastric pain the epigastric or right upper quadrant discomfort that occurs in preeclampsia can be marked, and may be out of proportion to the degree of liver enzyme abnormalities. it is believed to be caused by edema in the liver that stretches the hepatic capsule. in rare cases, it may be caused by hepatic infarction or rupture.

edema edema is present in more than 30% of normal pregnancies, and is thus not a reliable sign of preeclampsia. rapid weight gain (more than 1 lb per week in the third trimester) or edema in the hands or facial area (nondependent edema) is best viewed as a sign that should lead the clinician to evaluate the patient for other, more specific, evidence of preeclampsia.

Signshypertension

>140/90 mmhghypertension in preeclampsia is due to vasospasm and can be very labile. ideally, blood pressure should be

measured in the sitting position with a manual cuff, with the brachial artery at the level of the heart. there is a literature suggesting that some automated blood pressure cuffs may be less reliable in preeclampsia and that either a manual cuff or arterial line should be used to verify blood pressure in preeclamptic patients with severe hypertension (13).

epigastric or right upper quadrant tenderness

abdominal pain in preeclampsia is attributed to hepatic capsular stretching from edema. the degree of tender-ness is often out of proportion to the degree of elevation of liver function tests. epigastric tenderness is suggestive of severe preeclampsia, and is associated with an increased risk of both maternal and fetal adverse outcomes.

hyperreflexia Clonus is an important sign of preeclampsia but should be distinguished from the very brisk reflexes commonly seen in normal pregnancies.

retinal artery vasospasm on funduscopy

retinal vasospasm, retinal edema (in the form of soft exudates), hemorrhage, and exudative retinal detachment are uncommon findings in preeclampsia. Papilledema is rare.

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908 SECTion 8 the obStetriC GyneColoGiC Patient

rupture, occur in a minority of cases of preeclampsia. How-ever, these conditions are most likely to require intensive care and are therefore reviewed here in more detail.

Severe Hypertension

A single blood pressure threshold that would absolutely necessitate treatment in the setting of preeclampsia is not established. Expert opinion favors urgent treatment of blood pressures greater than 180 mmHg (systolic) and 110 mmHg (diastolic) and, in the setting of obvious hypertensive end-organ damage (retinal hemorrhage, papilledema, pulmonary edema, severe headache, or renal failure), the blood pressure should be kept under 160/100 mmHg; beyond this consensus, opinions vary considerably (18,19).

Although no evidence suggests that treating blood pres-sures between 160/100 and 180/110 mmHg in the setting of preeclampsia improves maternal or fetal outcomes, many experts believe that the risks for seizure, placental abruption, stroke, and cerebral hemorrhage are decreased by bringing blood pressures down into the normal or mildly hypertensive

range (20). Because preeclampsia is felt to be a dynamic vaso-spastic disorder with associated target-organ ischemia, some experts suggest letting blood pressures run in a moderately severe range to avoid worsening ischemia in areas of regional vasospasm. In the absence of direct evidence of end–target-organ damage from severe hypertension, it is our practice to treat all blood pressures over 160/105 mmHg. However, although we treat these blood pressures urgently, we are care-ful to avoid any severe, sudden decreases in maternal blood pressure that may adversely affect uteroplacental and cerebral perfusion.

If urgent blood pressure reduction is required, intravenous labetalol or intravenous hydralazine can be used. Increasing evidence indicates that labetalol may be the better choice of the two; it is our preferred agent, although both agents are still acceptable (20). Hydralazine has been associated with an increased risk of an emergency cesarean in women who receive it while still pregnant and with lower Apgar scores in the infants of mothers who have been given this agent prior to delivery. Short-acting oral nifedipine is also used at some

TablE 78.3 laboratory Features of Preeclampsia

Feature Description

Complete blood count with elevated hemoglobin and/or thrombocytopenia

the “elevation of hemoglobin” seen with preeclampsia (which may manifest as a hemoglobin of 12 g/dl at 37 wk, when it would be expected to be closer to 10 g/dl because of the physi-ologic dilutional anemia that is seen in pregnancy) is due to hemoconcentration. Much less commonly, hemoglobin may fall with preeclampsia due to a microangiopathic hemolytic anemia.

Platelet consumption in preeclampsia can cause an increased mean platelet volume and thrombocytopenia, and is an important manifestation of severe disease (14).

in severe cases of preeclampsia or hellP (a subset of preeclampsia), schistocytes (fragmented red cells) may be seen on peripheral smear and can lead to a mild drop in hemoglobin. brisk hemolysis is rare, however, and should lead to the consideration of hUS or ttP.

elevated serum creatinine typically serum creatinine is <0.8 mg/dl (70 μmol/l) in pregnancy and values greater than this are considered abnormal.

renal function impairment is caused by decreased renal blood flow and glomerular filtration rate secondary to swelling of intracapillary glomerular cells, fibrin deposition along the basement membranes, and afferent arteriolar spasm.

elevated serum uric acid typically, serum uric acid is <5.0 mg/dl (280 μmol/l) in pregnancy. Uric acid is the most sensitive test for identifying preeclampsia but it is still only elevated in approximately 80% of cases of preeclampsia. Uric acid rises in this setting due to impaired excretion of uric acid in the renal tubules that is caused by preeclampsia-related changes in the renal microcirculation (14). although an important sign of preeclampsia, the elevated uric acid level is distinct from an elevated creatinine, aSt, or decreased platelet count in that the uric acid level is not gener-ally believed to have any direct clinical consequences and should not be used as a marker of disease severity.

elevated liver enzymes Mild elevations of aSt, typically <100 U/l, suggest hepatic involvement. Greater levels may be due to severe preeclampsia, hellP syndrome, hepatic infarction, hepatic rupture, or superimposed acute fatty liver of pregnancy.

Proteinuria Proteinuria is an essential diagnostic feature of preeclampsia. Urine dipsticks are routinely used to screen for proteinuria in asymptomatic patients. however, dipsticks lack the needed sensitivity and specificity to make them a reliable test for proteinuria in patients in whom the diagnosis of preeclampsia is suspected because of the presence of other features of this disease. when preeclampsia is suspected, a 24-hour urine test for proteinuria with creatinine and creatinine clearance should be obtained. Proteinuria is present if there is more than 300 mg of protein excreted over 24 hours. total urinary creatinine should be measured to assess the adequacy of urine collection. the creatinine clearance can be used in conjunction with the serum creatinine as a measure of renal function.

the use of a random spot urinary protein-to-creatinine ratio to diagnose proteinuria in pregnancy has had many advocates, but it remains unclear at this time whether this test can replace the 24-hour urine in pregnant patients with suspected preeclampsia (15,16).

diC screen Severe preeclampsia can rarely cause diC, but it is almost always seen in association with throm-bocytopenia. Checking inr, Ptt, and fibrinogen degradation products is usually only done if the patient with preeclampsia has thrombocytopenia or is undergoing an invasive procedure.

hUS, hemolytic uremic syndrome; ttP, thrombotic thrombocytopenic purpura; aSt, aspartate aminotransferase; diC, dissemination intravascular coagulation; inr, international normalized ratio; Ptt, partial thromboplastin time.

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centers as an alternative to labetalol or hydralazine for the acute treatment of severe hypertension. Although its use in medical patients is now discouraged, its use for control of blood pressure in young pregnant or postpartum women with-out coronary artery disease remains an acceptable practice. Previous concerns about a drug interaction between magne-sium and calcium channel blockers appear to be ill-founded (21). Diuretics should not be used in this setting unless pul-monary edema is present because, despite the edema that is so common in preeclamptic patients, most hemodynamic studies of preeclamptic women suggest that they are actually intravas-cularly volume depleted.

Once the patient has delivered, any antihypertensive agent can be used for blood pressure control. At that point, nitro-prusside and nitroglycerin are excellent choices because of their very short half-lives.

Seizures

Seizures are the most well-known severe manifestation of preeclampsia. The risk of an eclamptic seizure in a patient with untreated preeclampsia is estimated to be about 1 in 200. Because of early identification of preeclampsia and the widespread use of magnesium prophylaxis, the incidence of eclampsia in the United States ranges from 1 in 1,000 to 1 in 20,000 deliveries; when it does occur, eclampsia is associated with a maternal mortality rate of 5% and a perinatal mortality rate between 13% and 30%.

Eclamptic seizures are typically of the grand mal vari-ety, with clonic–tonic muscular activity followed by a post-ictal period. However, focal, jacksonian-type and absence seizures have been described. Most eclamptic seizures occur in the setting of established preeclampsia with hypertension and proteinuria. Classically, they are preceded by evidence of neuromuscular irritability such as tremulousness, agitation, nausea, vomiting, and/or clonus. However, some patients will present with seizure as their first manifestation of pre-eclampsia, usually occurring in the absence of hypertension or proteinuria.

The onset of eclamptic convulsions can be antepartum (38% to 53%), intrapartum (18% to 36%), or postpartum (11% to 44%). Postpartum eclamptic seizures generally occur in the first 48 hours after delivery, but it is not unusual to see them occur anytime in the first week after delivery; eclamptic seizures have been reported as late as 23 days postpartum.

The underlying pathophysiology of the eclamptic seizure is unclear. They cannot be attributed simply to severe hyper-tension, because eclampsia can be seen in patients with only mild elevations in blood pressure. Electroencephalograms may show epileptiform abnormalities, but usually show only a nonspecific diffuse slowing that may persist for weeks after delivery. Computed tomography (CT) and magnetic resonance imaging (MRI) of the eclamptic patient can be normal, or may show findings ranging from diffuse edema to focal areas of hemorrhage or infarction. Symmetrical white matter edema in the posterior cerebral hemispheres, particularly the parieto-occipital regions is characteristic for reversible posterior leu-koencephalopathy syndrome (RPLS). Some suggest that RPLS could be considered an indicator of eclampsia, even when the other features of eclampsia (proteinuria, hypertension) are not present. MRI is more sensitive in detecting abnormalities in eclamptic patients, but both CT and MRI of the brain can be normal, particularly if done in the first 24 hours after the

seizure. When radiologic changes are present, some—but not all—of these changes usually resolve with time (22).

Management of Eclamptic Seizures

Even when delivery is impending, a preeclamptic woman should still receive an anticonvulsant to prevent eclamptic seizures; magnesium sulfate is the medication of choice for this purpose (23). It halves the risk of eclampsia in patients with preeclamp-sia and lowers the risk of recurrent seizures and maternal death in women with eclampsia. It is superior to phenytoin and ben-zodiazepines in preventing further seizures. Magnesium is typi-cally given as an intravenous bolus of 4 to 6 g, followed by a continuous intravenous infusion of 1 to 4 g/hr. Either monitor-ing plasma concentrations (which should run between 4 and 7 mmol/L), or observing the patient closely for symptoms and signs of toxicity (hypotension, hypotonia, muscular weakness, and respiratory depression) are reasonable options. Carefully monitoring for toxicity is important, particularly in patients with worsening renal function. Severe respiratory depression in a patient on magnesium should be treated with intravenous calcium. The only role of magnesium in preeclampsia is that of an anticonvulsant. Despite the possibility of a transient decrease in blood pressure with its initial administration, magnesium has no significant sustained effect on blood pressure. Its mecha-nism of action remains unclear, but it does not seem to have any intrinsic anticonvulsant effect, and may actually prevent seizures through its action as a cerebral vasodilator.

If the woman does have an acute eclamptic seizure, intra-venous benzodiazepine is indicated to acutely stop the seizure, and magnesium should then be initiated if this has not already occurred. If an eclamptic convulsion occurs while a patient is receiving magnesium, most clinicians will add phenytoin to the regimen. Continued seizures should warrant the involvement of neurology and consideration of the use of other antiepi-leptic drugs. Anticonvulsant therapy can generally be stopped once postpartum diuresis has begun and the manifestations of preeclampsia have started to improve.

Neuroimaging with CT or MRI is recommended for most patients with eclamptic seizures to rule out an intracerebral hemorrhage. The timing of these neuroimaging tests should be determined by the level of clinical suspicion for this diagnosis, and should not substantially delay delivery.

Cerebrovascular accidents

Cerebrovascular accidents are three to seven times more com-mon in pregnancy. Preeclampsia accounts for over a third of the strokes that do occur during pregnancy, and at least half of the deaths from preeclampsia in the developed world are due to stroke. Most of the strokes in patients with preeclampsia will be related to intracerebral hemorrhage, but can also occur due to vasospastic ischemia (24). Preeclampsia-related stroke is often, but not always, associated with severe hypertension and/or eclamptic convulsions. Sudden onset or worsening of a headache, a change in mental status, or any focal neurologic complaint occurring in the context of preeclampsia should lead to consideration of this diagnosis and urgent neuroimaging.

Pulmonary Edema

Pulmonary edema occurs in about 3% of cases of preeclamp-sia, and can cause significant maternal morbidity (25–27). It occurs as a result of the interplay of preeclampsia-related pulmonary endothelial damage and the low plasma oncotic

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pressure seen in all pregnancies; excessive intravenous fluid is also, typically, a contributing factor. It is often seen in the postpartum period after a patient has received a substantial amount of intravenous fluid in labor (or with cesarean deliv-ery) and when mobilization of fluid from the involuting uterus begins. Pulmonary edema in this setting is often amenable to gentle diuresis but may be severe enough to warrant mechani-cal ventilation.

Echocardiographic studies demonstrate that transient systolic or diastolic ventricular dysfunction is present in up to one-third of preeclampsia cases associated with pulmo-nary edema. This preeclampsia-related myocardial dysfunc-tion is believed to be a manifestation of vasospastic coronary ischemia, and usually resolves rapidly with resolution of the preeclampsia. We consider this to be a distinct entity from peripartum cardiomyopathy (PPCM) and do not believe there is a substantial recurrence risk of cardiac disease for these patients in a subsequent pregnancy.

Prevention and Treatment of Pulmonary Edema

It is important to avoid excessive fluid administration to patients with preeclampsia because of their propensity for pul-monary edema. Ideally, one individual should be designated to approve and monitor all fluid administration in these patients. Regular auscultation of the lungs and use of transcutaneous pulse oximetry in patients with severe preeclampsia will help identify cases of pulmonary edema as they evolve. This care-ful observation should be continued in the postpartum period because pulmonary edema often occurs as late as 2 to 3 days after delivery. Acute treatment of pulmonary edema should involve supplemental oxygen, low-dose furosemide, and, if needed, morphine (27,28). Blood pressure control may help treat pulmonary edema by decreasing afterload. An echocar-diogram should be obtained to look for an underlying car-diac contribution. Intubation and mechanical ventilation may become necessary if the above measures do not improve the patient’s oxygenation.

Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) can occur as a late and severe complication of preeclampsia or eclampsia (29). Because most patients with preeclampsia-related DIC have low platelet counts or elevated transaminase levels, DIC screening in the absence of these abnormalities is generally not necessary (30). However, a DIC screen should be ordered in all preeclamptic patients with rising liver enzymes, dropping platelet counts, and/or any abnormal bleeding. This is particu-larly important if there is a possibility of an operative delivery.

acute Renal Failure

Preeclampsia is often associated with a mild degree of renal impairment manifesting as a slightly elevated creatinine or a decreased urine output. This is due to a combination of intra-vascular volume depletion, renovascular vasospasm, and a preeclampsia-related glomerular lesion known as glomerular endotheliosis. This mild renal impairment usually resolves rapidly after delivery.

Acute renal failure in preeclampsia is not common. If it does occur, acute tubular necrosis (ATN) and partial or total cortical necrosis are the most likely underlying lesions, and are thought to be caused by preeclampsia-related, vasospasm-induced renal ischemia. A history of transient hypotension is

also typically present in these cases. The differential diagnosis includes ATN from sepsis or hemorrhage, or renal failure from causes unassociated with pregnancy such as hemolytic uremic syndrome, medication effects, or acute glomerulonephritis.

Most renal failure in the setting of preeclampsia is rapidly reversible, but if significant hypotension has occurred (as may happen with placental abruption or DIC-related hemorrhage), ATN or renal cortical necrosis may result and necessitate dial-ysis. In persons with sustained oliguria in the setting of pre-eclampsia, fluid challenges should be given cautiously because of the risk of pulmonary edema. Poor outcomes in preeclamp-sia are far more commonly related to pulmonary edema than they are to decreased urine output. Diuretics to improve urine output should be avoided in the absence of pulmonary edema because of the intravascular volume depletion present in most patients with preeclampsia.

If the patient is unresponsive to small fluid boluses, the use of central venous pressure (CVP) monitoring may be a helpful, if not completely reliable, guide. The role of the pulmonary artery catheter in this context is unproven, and should only be used by nurses and physicians who are trained and expe-rienced in its use. Increasing data from randomized control trials have shown that pulmonary artery catheters are of less benefit than previously believed in nonpregnant patients, and there is little reason to believe this tool has a uniquely benefi-cial role in the pregnant population.

Sustained oliguria in preeclampsia is unusual, and therefore significant and rapid peripartum renal deterioration should also lead to consideration of differential diagnoses that include the hemolytic uremic syndrome (HUS), thrombotic throm-bocytopenic purpura (TTP), and renal cortical necrosis. It is therefore advisable to perform careful microscopic examina-tion of urinary sediment and a peripheral smear in all pregnant or postpartum patients with oliguria (31).

HEllP Syndrome

A distinct clustering of the manifestations of preeclampsia is the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet counts). This constellation of findings represents a particularly severe form of preeclampsia with significant risk for maternal illness and fetal injury or death (32,33). HELLP occurs in up to 20% of cases of severe preeclampsia. The hemolysis is microangiopathic, and therefore schistocytes (fragmented erythrocytes) are seen on peripheral smears of the blood. Lactate dehydrogenase levels are usually increased and liver enzyme elevation may be two- to threefold. The thrombo-cytopenia can be precipitous and severe. High-dose dexameth-asone is often given to treat patients with HELLP, but it is not clear that this intervention has clinically significant effects on outcomes, and the treatment remains supportive care coupled with delivery (34,35).

Hepatic Rupture, Infarction, or Hemorrhage

Epigastric or right upper quadrant pain and elevation of hepatic enzymes due to preeclampsia are common. When these factors are present, it suggests severe disease and pre-eclampsia-related hepatic edema and ischemia. It generally is associated with no more than a two- to fourfold increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT). When pain is severe and/or hepatic enzymes rise above this level, preeclampsia-related hepatic infarction, hemor-rhage, and rupture should be considered and investigated with

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a hepatic ultrasound or CT (36). Acute fatty liver of pregnancy (AFLP) is also part of the differential diagnoses in these cases.

Diabetes Insipidus

Diabetes insipidus is a rare complication of preeclampsia with significant hepatic involvement. It can also be seen with AFLP. It has been hypothesized that the acute liver dysfunction in these patients reduces the degradation of vasopressinase (an enzyme which itself degrades vasopressin), and results in a state of relative vasopressin deficiency (37). The course of the condition follows that of the underlying disorder and can be treated with additional vasopressin until it resolves.

The Role of arterial lines, Central Venous Pressure Monitors, and Pulmonary artery Catheters in Preeclamptic Patients

Most severe preeclamptic patients have normal or hyperdy-namic left ventricular function with normal pulmonary artery pressure. Thus, a CVP monitor usually is adequate to assess volume status and left ventricular function. However, severely preeclamptic patients may develop cardiac failure, progres-sive and marked oliguria, or pulmonary edema. In such cases, some authors suggest that a pulmonary artery (PA) catheter may be helpful for proper diagnosis and treatment, because right and left ventricular pressures may not correlate (38,39). Given that evidence has evolved that the routine use of pul-monary artery catheters may not be as beneficial in the care of nonobstetric patients as once believed, the rather limited literature about their use in obstetric populations cannot help but be questioned (40–42). No clear consensus exists as to their role in the management of preeclampsia (43). We rarely employ them in any obstetric patients, as the risks— especially on labor and delivery units where the personnel have less experience in their placement and interpretation—seem to outweigh the evidence justifying their use. When questions arise as to whether cardiac dysfunction is contributing to a preeclamptic patient’s pulmonary edema and/or renal failure, we obtain an urgent bedside echocardiogram to guide our care and, in the absence of a significant cardiac cause, manage these patients clinically.

An intra-arterial catheter monitor may be indicated for protracted severe hypertension during therapy with potent antihypertensive agents or when there is a significant disparity between automated and manual cuff measurements of blood pressure.

CarDiaC Disease

Cardiac disease during pregnancy has an incidence rate of 0.4% to 4%, and is associated with a maternal mortality of 0.4% to 6%, depending on the cardiac lesion being discussed (44). Indeed, it is now the leading cause of maternal mortality in North America (45). Although rheumatic heart disease is far less of a concern in the West than it was several decades ago, it remains a problem, along with peripartum cardiomyopathy, pulmonary hypertension, adult congenital heart disease, and myocardial ischemia. These conditions will be the focus of this section. Although many of the patients with cardiac disease who end up under the care of a critical care physician will have cardiac disease that was identified prior to pregnancy, a sig-nificant portion of patients will also have their cardiac disease

present for the first time during pregnancy. The physiologic changes of pregnancy may exacerbate, and thereby unmask, previously undiagnosed cardiac disease, and pregnancy can predispose patients to the onset of certain cardiac diseases such as PPCM or ischemic heart disease. Some of the physi-ologic changes associated with pregnancy are reviewed below and are summarized in Table 78.4.

Physiologic Changes

Maternal blood volume gradually increases during pregnancy to 150% of nonpregnant levels (46). The increase in plasma volume (45% to 55%) is greater than the increase in red blood cell volume (20% to 30%), resulting in a relative anemia of pregnancy. This increase in blood volume is associated with an increase in cardiac output (CO), which begins early in gesta-tion and peaks at levels 30% to 40% over nonpregnant values between 20 and 30 weeks (46); the increase then plateaus until term. CO in a twin pregnancy is 15% higher than that of a singleton pregnancy (47).

The increase in CO with gestation is dependent on heart rate and stroke volume. Heart rate gradually increases throughout pregnancy, starting as early as 4 weeks of gesta-tion, with a 10% to 15% increase by term. Stroke volume, in contrast, peaks during the second trimester, with a 20% to 40% increase over the nonpregnant state.

During labor, CO rises another 15% to 45% above prela-bor values with an additional increase of 10% to 25% during uterine contractions. The increase in CO in labor during con-tractions versus that seen between contractions is greater late in the first stage (34%) versus early in the first stage (16%) (48).

Oxygen consumption increases 20% during pregnancy, and may increase as much as 40% to 100% during active labor. In

TablE 78.4 Hemodynamic Changes in Pregnancy

% Changea

Pregnancylabor and Delivery Postpartum

Cardiac output +30–50 +50–65b +60–80

heart rate +10–15 +10–30b –10–15

Stroke volume +20–30 +40–70 +60–80

blood volume +20–80 — +0–10

Plasma volume +44–55 — +0–30

red cell volume +20–30 — –10

oxygen consumption

+20 +40–100b –10–15

Systemic vascular resistance

–10–25 — —

Systemic blood pressure

Systolic –5 +10–30b +10

diastolic –10 +10–30b +10

Pulmonary vascular resistance

–30 — —

Pulmonary artery occlusion pressure (PaoP)

0 — —

Colloid oncotic pressure (CoP)

–10 — —

CoP–PaoP –25 — —

aPercentage change from nonpregnant state.bPercentage change without regional anesthesia (local anesthetic).

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the immediate postpartum period, CO increases 30% to 40% over the labor period or 60% to 80% over the nonpregnant state, with the increased blood volume shifting to the central circulation from the contracted uterus, as well as alleviation of aortocaval compression and a slight decrease in total periph-eral resistance.

CO and other hemodynamic parameters are thought to return to their baseline prepregnant state by 6 weeks after delivery. However, CO may remain elevated for up to 12 weeks (49).

Systemic arterial pressure decreases by 10 to 15 mmHg over the first two trimesters and then gradually returns to baseline by term. Systemic vascular resistance decreases 10% to 20% during pregnancy. Moreover, systemic vascular resistance may remain decreased for at least 12 weeks postpartum.

Venous pressure in the lower extremities increases and peaks near term as the gravid uterus compresses the inferior vena cava—especially when the patient is supine—while CVP remains unchanged. Total-body water increases by about 2 kg throughout pregnancy.

Invasive PA catheterization in low-risk, near-term pregnant patients (36 to 38 weeks) reveals a significant decrease in pul-monary vascular resistance, colloid oncotic pressure (COP), and COP–pulmonary artery occlusion pressure (PAOP) gradi-ent, with no change in PAOP or left ventricular stroke work index (50).

With a significant increase in oxygen consumption, espe-cially during labor, along with a decrease in functional resid-ual capacity, the importance of adequate preoxygenation (denitrogenation) before rapid sequence induction of anes-thesia cannot be overemphasized. Morbidity and mortality statistics from England and Wales reveal that anesthetic-related maternal mortality is predominantly caused by the inability to intubate the trachea or by pulmonary aspiration during general anesthesia (51). Thus, an awake orotracheal intubation should be considered when airway patency is suspect. The most experienced person available should typi-cally be the individual who intubates pregnant women on a regular basis.

Despite an average 200- to 500-mL blood loss for routine, uncomplicated vaginal deliveries and an 800- to 1,000-mL blood loss for cesarean section deliveries, blood transfusions are seldom necessary because of the increased blood volume and the autotransfusion of approximately 500 mL of blood from the contracted uterus in the postpartum period. Although this increase in blood volume protects against blood loss at delivery, pulmonary congestion and cardiac failure can result in patients with underlying cardiac dysfunction.

Pregnant women have a predisposition to pulmonary edema. Physiologic changes in pregnancy that favor the devel-opment of pulmonary edema include an increase in intravas-cular volume, decreased blood viscosity (“physiologic anemia of pregnancy”), decreased COP, and fluid shifts, especially in the immediate postpartum period.

Patients with minimal cardiac reserve may tolerate early pregnancy, and subsequently decompensate from increasing blood volume and the need for an increased CO in the late second trimester and early third trimester. Patients with mod-erate cardiac reserve may tolerate pregnancy well until labor and delivery or the puerperium. Thus, cardiac patients should continue to be closely monitored in the postpartum period because cardiac decompensation most frequently occurs

during this time; the prepregnant baseline state may not be reached for as long as 12 weeks after delivery.

The enlarging uterus in the third trimester predisposes to aortocaval compression and decreased CO in supine patients. Inferior vena cava compression occurs in up to 90% of near-term parturients in the supine position. However, only about 10% to 15% of patients manifest the supine hypotensive syn-drome because of shunting of venous blood away from the caval system to the azygos system by the intervertebral plexus of veins. Patients most susceptible to supine hypotension are those with polyhydramnios and multiple gestation. However, in most patients in the lateral position, CO is maintained. Turn-ing from the supine to the lateral decubitus position increases CO from 8% at 20 to 24 weeks to as much as 30% near term (52). Therefore, to avoid aortocaval compression, measures such as uterine displacement by maternal position (lateral decubitus), bed position (left lateral tilt), or uterine displace-ment devices are imperative, especially in the last trimester. Moreover, maternal hypotension and placental hypoperfusion from aortocaval compression can be compounded by regional anesthesia that interferes with compensatory sympathetic nervous system mechanisms (53).

As a consequence of these cardiovascular changes, normal symptoms of pregnancy can include fatigue, dyspnea, decreased exercise capacity, and lightheadedness. Cardiac signs that may be seen in normal pregnancies include distended neck veins, peripheral edema, loud first heart sound, loud third heart sound, systolic ejection murmurs, and continuous murmurs (cervical venous hums and mammary souffle). Fourth heart sounds and diastolic murmurs occur rarely in normal preg-nancy and should be considered pathologic unless proven oth-erwise. These changes are reviewed in Table 78.5. Therefore, the normal signs and symptoms of pregnancy may simulate pathologic disease states, thereby rendering the diagnosis of heart disease difficult.

TablE 78.5 Normal Cardiac Symptoms and Signs in Pregnancy

SYMPTOMSFatigue

dyspnea

decreased exercise tolerance

lightheadedness

Syncope

SIGNSGeneral

distended neck veinsPeripheral edemahyperventilation

heartloud S1; increased split S1

loud S3

Systolic ejection murmurContinuous murmurs (venous hums, mammary souffle)

Chest radiographincreased pulmonary vasculaturehorizontal position of heart

electrocardiogram

left axis deviation

nonspecific St-t–wave changes

Mild sinus tachycardia

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Normal chest radiographic findings demonstrate increased lung markings (prominent pulmonary vasculature partly due to both increased blood volume and increased breast shadow). Electrocardiographic (ECG) changes may include a left QRS axis deviation and nonspecific ST-segment and T-wave changes.

Who Is Most at Risk and When Is That Risk Greatest?

Table 78.6 classifies the risk of various cardiac lesions in pregnancy. When we speak about “risk” for these patients, we refer to congestive heart failure, arrhythmias, stroke, and death. Overall, about 13% of cardiac patients will suffer one of these outcomes in pregnancy. The presence of pulmonary hypertension is always associated with an increased risk, and this risk is commensurate to its degree of severity. Other

f actors associated with an increased risk of cardiac complica-tions in pregnancy include the following (54):• New York Heart Association (NYHA) functional class. This

is perhaps the most important predictor of pregnancy out-come. Patients with NYHA class I and II cardiac disease generally have a good prognosis during pregnancy. Patients with NYHA class III and IV are more likely to experience complications and may require special management around the time of delivery.

• Left-sided obstructive cardiac lesions. Patients with lesions such as aortic stenosis may have difficulty accommodating the increased blood volume and CO seen in pregnancy, and become increasingly symptomatic. Interestingly, patients with regurgitant valvular lesions may have less difficulty in pregnancy, as CO in these cases may benefit from the decrease in systemic vascular resistance seen in pregnancy.

• Cyanosis• Left ventricular systolic dysfunction• Prior cardiac events or previous dysrhythmia

Although pregnant women with cardiac disease may expe-rience complications at any point during pregnancy, there are three periods of particular risk:

1. At the end of the second trimester, when CO has increased to its peak

2. At the time of labor and delivery, when cardiac work may be increased dramatically by both pain and the autotransfusion of blood from the placenta and uterus with each contraction

3. In the first 72 hours following delivery, when the uterine involution and resolution of pregnancy-related edema leads to mobilization of large amounts of fluid

General Management of Cardiac Patients During Pregnancy

Management of patients with cardiac disease in pregnancy should, in general, include good preconception counseling to assess and inform the patient of the risks associated with a pregnancy. Although no woman should be told that she “should never get pregnant,” a clear discussion of the risk is essential. With cases such as severe pulmonary hypertension or Eisenmenger syndrome, the patient should be strongly cau-tioned against pursuing a pregnancy. Women with congenital heart disease need also be informed that they are at increased risk of giving birth to a child with congenital heart disease. If a woman with cardiac disease decides to pursue a pregnancy after a clear discussion of risk, the cardiologist should ensure that her cardiac status is clearly delineated and optimized. Ide-ally, any necessary investigations or interventions should be carried out prior to conception. Once a woman is pregnant, regular visits with a medical specialist and an obstetrician trained in the care of high-risk pregnancies to watch for evi-dence of heart failure and arrhythmias are essential. Consulta-tion with an obstetric anesthesiologist prior to delivery is also prudent.

As stated earlier, most cardiac medications can be used in pregnancy when indicated. Table 78.7 lists many common car-diac medications, and classifies them as to which drugs we know the most about regarding their safe use during preg-nancy and which drugs we know the least. However, it should be emphasized that among the more commonly used cardiac

TablE 78.6 Peripartum Risk of Various Cardiac lesions

Risk Category lesion

lower-risk lesion Mitral valve prolapse

Mitral valve prolapse with regurgitation

atrial septal defect

Ventricular septal defect with normal pulmonary pressures

trace to mild valvular regurgitation

nyha class i

history of SVt with recent good control

Presence of an implanted pace maker

intermediate-risk lesion

Stable ischemic heart disease

Mild to moderate pulmonary hypertension

Moderate to severe valvular insufficiency

nyha class ii

Cardiomyopathy with ejection fraction 30–50%

Poorly controlled SVt

high-risk lesion Unstable ischemic heart disease

Moderate to severe left ventricular obstruction (e.g., aortic <1.5 cm2 or mitral valvular stenosis <2 cm2, peak gradient lV outflow tract of >30 mmhg)

nyha class iii

Cardiomyopathy with ejection fraction <30%

dilated aortic root, Marfan syndrome, ehlers–danlos syndrome

Moderate pulmonary hypertension

history of ventricular tachycardia with or without aiCd

Mechanical prosthetic heart valve

history of tia or CVa

highest-risk lesion Pulmonary hypertension >80 mmhg

eisenmenger syndrome

nyha class iV

Cyanosis

nyha, new york heart association; SVt, supraventricular tachycardia; aiCd, auto-mated implantable cardioverter-defibrillator; tia, transient ischemic attack; CVa, cerebrovascular accident.

items above can be used to calculate a risk index with 1 point being assigned for each and 0, 1, and >1 points being associated with a risk of some cardiac event during the entire pregnancy of 5%, 27%, and 75%, respectively.

risk calculation adapted from Siu S, Sermer M, Colman JM, et al. Prospective multi-center study of pregnancy outcomes in women with heart disease. Circulation. 2001;104:515.

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medications, only angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and warfarin are known or strongly suspected to be human teratogens. Amiodarone has had mixed data with respect to its safety in pregnancy, with some reports of congenital hypothyroidism, goiter, prema-turity, hypotonia, and bradycardia (55,56). Although use in an acute setting is appropriate, it is not a first-line agent for maintenance therapy in pregnancy. Angiotensin-converting enzymes and angiotensin receptor blockers both have been associated with fetal anomalies, fetal loss, oligohydramnios, cranial ossification abnormalities, and neonatal renal failure. Although their use in the first trimester was once supported, recent evidence suggests they should not be used at any time in gestation (57). Warfarin is associated with a high risk of mis-carriage and anomalies of the eyes, hands, neck, and central nervous system (58). Again, the guiding principle of managing

critical illness in pregnancy should be that, because fetal well-being depends on maternal well-being, medications that are of benefit to maternal health should also be considered to be in the fetus’ best interest. Useful sources for reviewing the avail-able safety data for medications during pregnancy and with breastfeeding are found in references (59–65).

For any structural cardiac lesion, we typically will obtain an echocardiogram as a baseline early in pregnancy, in the third trimester, and with any change in clinical status. Addi-tional investigations and interventions should be dictated by the patient’s clinical status, and no needed test or procedure should be withheld during gestation. In particular, pregnancy should not limit necessary diagnostic testing (66). Ultrasound has a long history of safe use in pregnancy. The radiation expo-sure associated with plain film radiographs, nuclear medicine scans, angiography, and CT scans are all well below what is

TablE 78.7 Commonly Used Cardiac Medications and Their Safety in Pregnancy

Use Generally Justifiable for This Indication in Pregnancy

Use Justifiable in Special Circumstances for This Indication in Pregnancy

Use almost Never Justifiable for This Indication in Pregnancy

Dysrhythmia digoxin amiodarone

β-blockers (all probably safe but most avoid propranolol and atenolol, which may cause intrauterine growth restriction)

Calcium channel blockers, especially verapamil and diltiazem (less known about amlodipine)

disopyramide, mexiletine, and fle-cainide (less is known about these agents in pregnancy but there is no evidence at this point of human teratogenesis; they should generally be considered second-line agents in pregnancy)

adenosine

Quinidine

Procainamide

lidocaine

ischemia nitrateslow-dose (<100 mg) aSaβ-blockersheparin (unfractionated or low

molecular weight)tissue plasminogen activatorStreptokinase

hMG-coa reductase inhibitors (“statins”) have concerning animal pregnancy data, but very limited reported human experiences thus far have been encouraging; should only be used in pregnancy when short-term benefits are clear

warfarin

abciximab (and other glycoprotein iib/iiia inhibitors) dipyridamole, ticlopidine, and clopidogrel lack published human data; they are probably safe but should only be used in pregnancy when short-term benefits are clear

heart failure Furosemidedigoxinhydralazine

nitroprusside (fetal cyanide toxicity possible at high doses)

aCe inhibitorsangiotensin ii receptor

blockers

β-blockers

dopamine

dobutamine

hypertension labetalolβ-blockersnifedipinehydralazineMethyldopa

thiazide diuretics (in this category for the treatment of hypertension because of effects of blood volume in pregnancy)

Clonidine, prazosin, verapamil, diltiazem, and amlodipine (in this category for the treatment of hyper-tension because of limited data on safety and the availability of many good alternatives with more data)

aCe inhibitorsangiotensin ii receptor

blockers

nitroprusside (fetal cyanide toxicity possible at high doses)

aSa, acetylsalicylic acid; aCe, angiotensin-converting enzyme.

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deemed acceptable during pregnancy. Contrast agents appear to be well tolerated by the fetus. MRI has not been associated with any ill effects in human pregnancies. Because fetal well-being is dependent on maternal well-being, more harm will generally be caused to a mother and her fetus by withholding necessary investigations than by obtaining them.

Women with congenital heart disease should undergo a detailed fetal ultrasound in the early second trimester to allow early diagnosis of congenital heart disease in the fetus. This will allow informed decision-making by the mother, and will prepare the neonatology team should a problem be present.

Labor and delivery and the first 72 hours postpartum warrant special consideration with respect to assembling the appropri-ate team and determining what monitoring will be needed. For most cardiac patients, a multidisciplinary patient care confer-ence should be assembled well in advance of the anticipated time of delivery and a written care plan developed for the peripartum management of the patient. This team should generally include representation from critical care, nursing, anesthesia, obstetrics, and cardiology. The plans that are developed should be explicit and detailed and recognize that the labor and delivery room is a place where cardiac care is not commonly provided. Even the best-trained obstetricians and obstetric nurses will lack the volume of experience in the management of cardiac cases that is common among cardiac and critical care providers. It is our conviction that joint nursing of such patients by obstetric and cardiac-trained nurses during labor and delivery, followed by postpartum care in a cardiac or critical care unit, seems the ideal approach when possible. Table 78.8 offers a comprehensive checklist of parameters to be considered and addressed in a mul-tidisciplinary patient care conference dedicated to developing a labor and delivery plan for a cardiac patient.

The mode of delivery should not generally be determined by medical concerns. The need for cesarean deliveries is gen-erally dictated by obstetric concerns, and vaginal deliveries should generally be viewed as the safest and best option for cardiac patients. The choice between spontaneous labor and elective induction of labor should be made both on the likeli-hood of successful induction and the availability of medical expertise and resources should a cardiac patient go spontane-ously into labor during the off hours and weekends.

Most patients should be kept in neutral fluid balance over the course of their delivery period, and careful monitoring of both input and output will be essential. Early and good anes-thesia is important to decrease the cardiac work of delivery, and most patients should receive regional anesthesia in a man-ner that will minimize the need for the fluid boluses typically given to decrease the hypotension associated with establishing regional anesthesia. It is also important to consider that cer-tain lesions, such as an aortic stenosis, may be highly volume dependent and require this additional fluid support.

Intra-arterial lines are advisable for cardiac lesions for which moment-to-moment monitoring of blood pressure might be desirable, such as severe aortic stenosis. The role of the pulmonary artery catheter in the laboring patient remains unclear and, in the absence of clear benefit, it is this author’s opinion that their use during delivery should be limited to the most severe cardiac cases, if it is used at all.

Bacterial endocarditis prophylaxis is no longer recom-mended by the American Heart Association for vaginal or cesarean deliveries because the bacteremia associated with delivery is unlikely to cause endocarditis (67). If done at all,

endocarditis prophylaxis should be reserved for patients with prosthetic heart valves, a prior history of subacute bacterial endocarditis, complex cyanotic congenital heart disease, or surgically constructed systemic pulmonary shunts or conduits, and an agent active against enterococci such as penicillin, ampicillin, or vancomycin should be utilized.

It is critical that all team members recognize that the car-diac patient remains at risk for at least 72 hours postpartum, so despite the sense of completion that comes with a successful delivery, caregivers need to remain vigilant for early signs of deterioration in the days following the birth.

Specific lesions

Mitral stenosis. Rheumatic heart disease remains a potential form of heart disease in pregnancy despite its declining inci-dence in the developed world. Mitral stenosis (MS) accounts for approximately 90% of the rheumatic valvular lesions in pregnancy. It often presents for the first time in pregnancy; complications include atrial fibrillation, pulmonary edema, and thromboembolic stroke. The normal physiologic car-diac changes in pregnancy are poorly tolerated in MS. Most patients will experience some worsening of symptoms during pregnancy, and the risk continues during labor and delivery as the increased blood volume after delivery of the placenta may worsen pulmonary edema (68). Complication rates were found in one study to be 38% in moderately severe MS and 67% in severe cases (69). Avoidance of tachycardia (which decreases time available for ventricular filling), increased PA pressure, decreased systemic vascular resistance, and increased central blood volume are essential to patient management. For this reason, many patients will benefit from β-blockade to improve left ventricular filling time during pregnancy (70). Echocardio-grams should be done once every trimester and with any change in status in these patients. Careful attention should be focused on pulmonary pressures (although echocardiography may pro-vide a less reliable estimate of pulmonary pressures in preg-nancy). Pulmonary edema should be treated with diuretics and β-blockade. If severe symptoms persist despite optimal medical management, percutaneous mitral balloon valvuloplasty, com-missurotomy, or even valve replacement may be warranted; all have been successfully performed in pregnancy (71–73). Open procedures may be associated with a higher risk of miscarriage, fetal loss, and preterm labor, and thus balloon valvuloplasty may be preferable at centers experienced with this procedure. Although surgery can be performed at any point in the preg-nancy, the risk to the fetus is lowest in the second trimester.

If atrial fibrillation occurs, it should be treated promptly to decrease tachycardia and the associated risk of a low CO state or degeneration into more malignant dysrhythmias. Rate control, full anticoagulation with heparin, and consideration of either medical or electrical cardioversion remain the core management principles in pregnant women with atrial fibrilla-tion as they are for nonpregnant women.

For labor and delivery (vaginal or cesarean), excellent pain control is important and is best achieved with early establish-ment of regional anesthesia. Control of pain will limit the undesirable effects of labor on heart rate and blood pressure (which are tachycardia and increased systemic vascular resis-tance). A conservatively dosed lumbar epidural anesthetic with special attention to fluid status, left uterine displacement, and careful use of α-adrenergic agents to treat hypotension is often helpful. These patients are dependent on high left ventricular

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TablE 78.8 Cardiac Patient Delivery Plan Checklist

PRIOR TO HOSPITalIZaTIONis additional testing needed to assess risk or guide peripartum therapy? Consider for all levels of risk.

•baseline eCG done in third trimester•echocardiogram at any time in the past for lowest-risk lesions, in this pregnancy

for moderate-risk lesions, and in the third trimester for high- and highest-risk lesions

•Stress testing (exercise echo or dobutamine echo in past year for patients with known or suspected ischemic heart disease or more recently if they are symptomatic)

•eP testing for life-threatening dysrhythmia (investigation often deferred until postpartum but can be done in pregnancy if warranted)

has the patient’s cardiac status been optimized? Consider for all levels of risk.

• is medical therapy optimized and have appropriate dose adjustments been made for the changes of pharmacokinetics in pregnancy?

•are there interventions that would be done if the woman was not pregnant that should be done while she is pregnant to optimize patient’s status for deliv-ery (e.g., diagnostic or therapeutic cardiac catheterization [angioplasty, stent], valvuloplasty, valve replacement, diagnostic or therapeutic eP studies, aiCd or pacemaker placement or adjustment)?

•Multidisciplinary team meeting needed and arranged (generally should have occurred by 34 wk). team should include:• nursing (ldr and postpartum care rn +/– iCU/CCU nursing)• Maternal fetal medicine• anesthesia (ideally obstetric anesthesia, also consider cardiac anesthesia

for high- and highest-risk cases)• Cardiology• iCU/CCU doctor

Consider having meeting of rn/MFM/anesthesia for moderate-risk patients and all of the listed providers for high- and highest-risk patients.

•written delivery plan should be generated and distributed and made avail-able to all relevant parties including nursing (should include who to call and how to do so when the patient comes in)

Consider for all levels of risk.

•Case-specific nursing education should occur in advance of delivery. Consider for all levels of risk. For lowest-risk lesions it may be adequate to have a standardized nursing care plan or the written delivery plan.

INTRaPaRTUMdetermine mode and timing of delivery:•Planned induction at what gestation/cervical status•Planned cesarean delivery at what gestation•Spontaneous delivery

decision to be made on the basis of obstetric factors and the need to ensure availability of necessary members of the care team. Planned delivery may be advisable for high- and highest-risk patients.

delivery location:•Standard ldr•Specialized ldr•obstetric iCU•MiCU•CCU

decision to be made on the basis of local facilities and expertise. in general, care during delivery is best pro-vided in ldr and afterward in medical setting.

delivery personnel who should be notified of admission (make sure needed parties available on day of any planned delivery)

Consider having both ldr nurse and critical care nurse for high- and highest-risk patients.

Medical attendants:

•obstetrician•Cardiologist•anesthesia (ideally obstetric anesthesia; also consider cardiac anesthesia

for high- and highest-risk cases)• intensivist

nursing (Consider need for team approach of iCU/CCU/rr/er nurse with ldr nurse. define necessary nurse-to-patient ratio):

•ldr nurse•ldr nurse with aClS training•ldr nurse with aClS and special critical care training•Critical care nurse (iCU/CCU/rr/er) nurse

Consider required response time of aClS trained per-sonnel if nursing team caring for patient is not aClS certified/experienced

this question is particularly important for free-standing obstetric centers.

edUCation

•Verify written care plan is available to all team members• is a “recap” in-service for care team advisable on day of delivery?

Consider summary in-service on day of delivery for high- and highest-risk patients and any patient for whom medications may be required urgently that are not routinely used on obstetric floors.

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MonitorinG•Cardiac monitor options (choose one)•not necessary•to be in room but does not need to be on if patient asymptomatic•to be on patient at all times but not continuously observed•to be on patient at all times and should be continually observed by

aClS-trained individual•to be on patient at all times and should be observed at all times by critical

care nurse/Md/Pa/rnP

Most cardiac patients, aside from the highest-risk patients or those with a history of life-threatening hemodynamically unstable arrhythmias, will not need continuous monitoring by aClS-trained person-nel. low-risk lesions may warrant one of the first two approaches. Moderate- and high-risk lesions may warrant only option 3.

Pulse oximeter (choose one)•not necessary•readily available but use only with symptoms• in room and check hourly• in room and on continuously

Pulse oximeter may provide evidence of ChF but should always be interpreted in view of strength of pulse signal. option 2 is probably adequate for most cardiac patients aside from those with cyanotic heart disease or those in ChF, who probably warrant option 4.

Fetal monitoring obtain explicit plan from obstetric team including who will read the fetal monitoring strips and the plan of action should they be concerning.

defibrillator•on the unit with ready access to defibrillator pads•defibrillator and defibrillator pads in the room•defibrillator pads on patient but machine not hooked up•Patient to be monitored using defibrillator with defibrillator pads

option 1 is generally adequate. Consider other options in highest-risk patients.

iV access•no iV necessary•Single peripheral iV lines needed•two peripheral iV lines needed•Central line•Central line with CVP•Central line with pulmonary artery catheter

option 2 is enough for most patients. Consider central line in highest-risk lesions.

FlUID balaNCEall patients need strict ins and outs measured throughout hospitalization.

Most cardiac patients we will want to keep in a neutral fluid balance during hospitalization.

Make sure to add in all fluids given with medications and for regional anesthesia.

Fluid to be run:

rate:

arterial line•no arterial line needed•arterial line warranted

arterial line advisable when hemodynamics make moment-to-moment monitoring of blood pressure useful (e.g., aortic stenosis)

MediCationS•need for Sbe prophylaxis (Sbe prophylaxis for high-risk lesions only and even

then not absolutely necessary)•Special issues related to interactions with commonly used obstetric

medications•Possibly necessary cardiac medications not routinely used on obstetric

units• need for rn/Md education regarding these medications• need for written instructions with respect to preparation and administration

of this medication• need for medication to be at bedside• Pharmacy notified in advance of request (especially if free-standing

obstetrics hospital)

May be given for prosthetic heart valves, prior Sbe, complex cyanotic congenital heart disease, surgi-cally constructed systemic pulmonary shunts or conduits but not necessary for the rest

•Standard dosing: ampicillin 2 g iV plus gentamicin 1.5 mg/kg within 30 min of delivery; ampicillin 1 g iV 6 h after delivery

•Penicillin allergy: Vancomycin 1 g iV over 1–2 h plus gentamicin 1.5 mg/kg iV within 30 min of delivery

anesthetic concerns•Special issues related to anesthesia•Special issues with respect to cautery for cesarean delivery

anesthesia will determine preferred modality of anesthesia timing and precautions in technique.

implanted defibrillators may need to be turned off prior to surgery because of interference from cautery.

thromboprophylaxis• intermittent compression stockings•heparin 5,000 units SQ q12h•heparin 5,000 units SQ q8h•enoxaparin 40 units SQ daily•enoxaparin 30 units SQ q12h•Full anticoagulation necessary in peripartum period (please see

peripartum anticoagulation protocol)

options 1 and 2 compatible with epidural anesthesia. options 3–6 should only be done after the epidural catheter is removed. Consider option 1 or 2 antepar-tum and option 2, 3, 4, or 5 for most patients postpar-tum while in hospital.

TablE 78.8 Cardiac Patient Delivery Plan Checklist (Continued )

(Continued )

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POSTPaRTUMhow long postpartum will patient require special observation?•Usual period of postpartum observation•6 h•12 h•24 h•48 h•72 h•96 h

low-risk patients probably only warrant the usual period of observation given all patients. Moderate-risk patients warrant 6 h. high-risk patients warrant between 6 and 48 h and highest-risk patients 72–96 h.

location of special postpartum observation•room on regular postpartum floor•room on high-risk antenatal floor•Standard ldr/postop CS area•Specialized ldr/postop CS area•obstetric iCU•MiCU•CCU•other

option 1, 2, or 3 for low-risk; 2, 3, or 4 for moderate-risk; and 4, 5, 6, or 7 for high- and highest-risk patients

MonitorinGCardiac monitor options (choose one)•not necessary•to be in room but does not need to be on if patient asymptomatic•to be on patient at all times but not continuously observed•to be on patient at all times and should be continually observed by

aClS-trained individual•to be on patient at all times and should be observed at all times by critical

care nurse/Md/Pa/rnP

option 1 or 2 for low-risk; 2 or 3 for moderate-risk; 3 for high-risk; and 3, 4, or 5 for highest-risk patients

Postpartum monitoring/interventions recommended and for how long•Peripheral iV•Central line•CVP•arterial line•Pulmonary artery catheter

no special monitoring or interventions for low-risk patients; 1 for 24 h for moderate-risk patients; and 1 or 2 for 48–72 h for high- and highest-risk patients

all patients need strict ins and outs measured throughout hospitalization. Most cardiac patients we will want to keep in a neutral fluid balance during hospitalization.

Make sure to add in all fluids given with medications and for regional anesthesia.

Fluid to be run:

rate:

Pulse oximeter in room and checked how often•not necessary• in room but use only with symptoms• in room and check hourly• in room and on continuously

Pulse oximeter may provide evidence of ChF but should always be interpreted in view of strength of pulse signal. option 2 probably adequate for most cardiac patients aside from those with cyanotic heart disease and those in ChF, who probably warrant option 4.

availability of aClS trained physician/Pa/rnP:•Special availability not necessary•Special availability necessary with what maximum response time

Postpartum care team: identify the care team and circle who will be the initial contact should medical problems arise. Make sure the person’s name and contact number are clearly documented in the chart.

Consider required response time of aClS-trained personnel if not present

Medical attendants:•obstetrician•Cardiologist•anesthesia (ideally obstetric anesthesia; also consider cardiac anesthesia

for high- and highest-risk cases)•General internist• iCU team•CCU team•Medical iCU vs. ldr with cardiac nursing (consider need for team

approach and necessary nurse-to-patient ratio)•ldr nurse•ldr nurse with aClS training•ldr nurse with aClS and special critical care training•Critical care (iCU/CCU/rr/er) nurse

defibrillator•on the floor• in the room•Pads on patient•Patient to be monitored with defibrillator pads on•Special issues related to interactions with commonly used obstetric

medications

option 1 is generally adequate. Consider other options in highest-risk patients.


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thromboprophylaxisStartdUration• intermittent compression stockings•heparin 5,000 units SQ q 2h•heparin 5,000 units SQ q8h•enoxaparin 40 units SQ daily•enoxaparin 30 units SQ q12h•Full anticoagulation will be needed postpartum: See peripartum

anticoagulation protocol•Possibly necessary cardiac medications not routinely used on obstetric

units• need for rn/Md education regarding these medications• need for written instructions with respect to preparation and administration

of this medication• need for medication to be at bedside• Pharmacy notified in advance of request (especially if free-standing

obstetric hospital)

DISCHaRGE PlaNNINGwill there be any adjustments to medication necessary postpartum (e.g.,

resumption/replacing of medications stopped/started because of pregnancy or dosing adjustments necessary in postpartum period because of increases made during pregnancy)?

who will follow the patient after discharge and when will patient need to be seen (letter or phone call should be sent/made to receiving Md):

•Cardiology•Primary care doctor•obstetrics

eCG, electrocardiogram; eP, electrophysiologic; aiCd, automatic implantable cardioverter-defibrillator; ldr, labor and delivery room; rn, registered nurse; iCU, intensive care unit; CCU, critical care unit; MFM, maternal–fetal medicine; MiCU, medical intensive care unit; rr, recovery room; er, emergency room; aClS, advanced Cardiac life Support; Md, doctor; Pa, physician assistant; rnP, registered nurse practitioner; ChF, congestive heart failure; CVP, central venous pressure; Sbe, subacute bacterial endocarditis; CS, cesarean section.


filling pressures for their CO (74,75). Obstetricians will gener-ally try to limit the second stage of delivery (the “pushing” stage) and assist a prolonged second stage through the use of vacuum extractors or forceps to decrease maternal work. The role of pulmonary artery catheters and intra-arterial lines for cardiac patients in labor was discussed previously and remains unclear. If there is a group who benefits from these interven-tions, it will likely be those patients with severe obstructive lesions or very poor ejection fractions. If the pulmonary artery catheter is used for patients with MS, it will be important to remember that the PAOP may overestimate left ventricular end-diastolic pressure.

aortic Stenosis

Aortic stenosis is a valvular lesion rarely seen during preg-nancy, and can be of rheumatic or congenital origin. Although bicuspid aortic valves are common, they are unlikely to be associated with significant stenosis in the childbearing years. They may be associated with an increased risk of both coarcta-tion and dissection. Although mild to moderate aortic stenosis is generally well tolerated in pregnancy, severe stenosis (defined as <1.0 cm2) carries a significant fetal and maternal risk. The rate of complication varies from 10% to 31%, depending on the severity of the lesion (76–78). Ideally, symptomatic aortic stenosis should be repaired prior to pregnancy. If the patient is classified as NYHA functional class III or IV while pregnant, consideration should be given to percutaneous valvuloplasty, surgical repair, or valve replacement. Ideally, such procedures are best done in the middle of the pregnancy but, if neces-sary, can be done at any time. When severe disease is identified after the first trimester, it is important to be aware that both

labor and delivery and a late termination are associated with significant risks. Due to the fixed outflow obstruction, these patients will not tolerate sudden drops in volume or preload, and their peripartum period should be managed in such a way as to minimize the risk of such events and ensure the ability to respond rapidly if and when they do occur. Arterial lines are strongly advised, and the use of pulmonary artery catheters, while not proven, may be of benefit.

In the past, with severe stenotic lesions of the aorta, regional anesthesia has been avoided because of the result-ing local anesthetic–induced sympathectomy, which can lead to bradycardia and decreased venous return. However, good results have been obtained in patients with severe aortic ste-nosis managed during labor with a carefully titrated epidural anesthetic (78,79).

Mitral and aortic Insufficiency

Mitral insufficiency is the second most common valvular lesion seen in pregnancy, and is typically due to rheumatic heart dis-ease (75). Aortic insufficiency is less common, and may be due to rheumatic, infectious, or rheumatologic conditions. These lesions, when found in isolation, tend to do well in pregnancy unless there is associated ventricular decompensation. Treat-ments when symptomatic may include diuretics, β-blockers, or vasodilators, but angiotensin receptor blockers should not be used despite the benefits of afterload reduction. Increases in systemic vascular resistance, decreased heart rate, atrial dys-rhythmias, and myocardial depressants may be poorly toler-ated. Perhaps the most important peripartum issue for these patients is early regional anesthesia to prevent pain-associated increases in systemic vascular resistance.

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Congenital Heart Disease

Approximately 25% of heart disease in pregnancy is congeni-tal. It can be categorized as left-to-right shunt, right-to-left shunt, and aortic lesions.

left-to-Right Shunt

The most common congenital heart lesions are atrial septal defects (ASDs) and ventricular septal defects (VSDs), which are usually well tolerated in pregnancy. The risk of car-diac complications is greatest in patients with large defects. Congestive heart failure (due to increased blood volume in pregnancy leading to cardiac decompensation), atrial dys-rhythmias, shunt reversal (occurring due to sudden systemic hypotension), and thromboembolic disease are all possible complications seen with ASD and VSD in pregnancy. Ideally, hemodynamically significant septal defects should be repaired prior to pregnancy. However, when symptomatic septal defects present in pregnancy, the principles of management include (a) acetylsalicylic acid (ASA) 81 mg daily to prevent thromboem-bolism, (b) use of diuretics and digoxin to treat heart failure, (c) avoidance of hypotension with epidural administration or postpartum blood loss, and (d) rapid rate control with any arrhythmia.

Right-to-left Shunt and Pulmonary Hypertension

The high-risk congenital disorders in pregnancy include right-to-left shunts, as seen in Eisenmenger syndrome (any con-genital heart lesion with a bidirectional or right-to-left shunt at the atrial, ventricular, or aortic level), and any other lesions asso-ciated with significant pulmonary hypertension. Patients with uncorrected cyanotic heart disease have increased spontaneous abortion rates, pulmonary embolization, congestive heart fail-ure, and incidence for congenital heart defects in the fetus. A high hematocrit (≥65%) is not only an indication of the severity of the cardiac disease, but also in itself has a poorer prognosis secondary to complications from hyperviscosity (decreased CO, organ hypoperfusion, and thrombosis).

During pregnancy, right-to-left shunting is increased because of decreased systemic vascular resistance, resulting in decreased pulmonary artery perfusion and hypoxia. A review on maternal and fetal outcome in patients with Eisenmenger syndrome reveals maternal mortality rates of 25% to 52% and fetal loss as high as 44% (80–82). Because of the grim prog-nosis for these pregnancies, these women should be strongly warned about the dangers of pursuing a pregnancy and, if they do become pregnant, should be offered the opportunity for an early termination. If they continue with the pregnancy, they may warrant hospitalization from 20 weeks onward. Oxygen should be administered for dyspnea, and prophylactic heparin should be considered throughout pregnancy and for 6 weeks postpartum. The mode of delivery should be determined on the basis of obstetric indications. Pulmonary artery catheter-ization can carry additional risks in patients with significant pulmonary hypertension, and should probably be avoided in these patients. Active efforts should be made to avoid sud-den decreases in systemic vascular resistance, blood volume, and venous return. Increased pulmonary vascular resistance promotes right-to-left shunting; therefore, hypercapnia and hypoxia are to be avoided. How best to provide peripartum anesthesia to these patients is not clear, and discussion of this

matter is beyond the scope of this chapter. What is clear is that if regional anesthesia is used, care must be taken to pre-vent precipitous drops in venous return. Patients with pul-monary hypertension and/or Eisenmenger syndrome should be observed for 72 hours postpartum in a cardiac setting, as many of the maternal deaths associated with these conditions will occur during this period.

aortic Disease

Coarctation of the aorta and aortic manifestations of Mar-fan syndrome pose significant problems in pregnancy (83–85). The physiologic changes during pregnancy, including increased blood volume and increased blood pressure during labor and delivery, may promote aortic dissection in either of these conditions. Patients with coarctation of the aorta may also suffer from worsening hypertension or congestive heart failure in pregnancy.

Marfan syndrome is often associated with aortic dilation, aortic valve regurgitation, and mitral valve disease. Aortic dis-section occurs in about 10% of patients with Marfan syndrome who undergo a pregnancy, and is most likely to occur if the aor-tic root measures beyond 4.5 cm in diameter (86,87). Ideally, women with this severity of aortic root dilation should have their aorta repaired prior to pregnancy. However, if they have not, serial echocardiography during pregnancy to watch for worsen-ing dilation should be performed. If the root is increasing in size, aortic repair should be considered. The activity of patients with significant aortic dilation in pregnancy should be limited, and they should be placed on β-blockers to decrease shear stresses upon the vessel wall (88,89). Although we generally teach that the indications for cesarean delivery are obstetric and not medi-cal, it is common practice to deliver women with aortic roots dilated beyond 4.0 cm by cesarean to avoid additional stress on the aorta associated with the pain and pushing of a vaginal delivery. However, it is worth noting that the majority of aortic dissections in these patients occur prior to the onset of labor.

Aortic coarctation in pregnancy is associated with an increased risk of worsening hypertension and, less commonly, congestive heart failure or preeclampsia (90). It is much less likely to be associated with aortic dissection than Marfan syndrome, but dissection can and does occur. Blood pressure should be kept less than 160/100 mmHg in these patients but not brought below 120/70 mmHg, as there may be a significant gradient between blood pressure measurement in the arm and the estimated blood pressure of the placenta circulation that is distal to the aortic narrowing. β-Blockers are the preferred antihypertensives for these patients. Patients with coarctation can undergo a vaginal delivery but should have a limited sec-ond stage (i.e., prolonged pushing should be avoided by the use of vacuum extractor or forceps).

Tetralogy of Fallot

Tetralogy of Fallot is the most common cyanotic congenital heart disease. It consists of a VSD, an overriding aorta, infun-dibular pulmonary stenosis, and secondary right ventricular hypertrophy. Patients with uncorrected tetralogy have sig-nificant complications in pregnancy including biventricular failure, dysrhythmias, stroke, and risk of shunt reversal with worsening cyanosis. Preconception surgical repair should be undertaken if at all possible. If these patients do proceed with a pregnancy unrepaired, they should be managed in a manner similar to patients with Eisenmenger syndrome.

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Patients with a surgically corrected tetralogy of Fallot who enter a pregnancy with a good functional status generally tolerate pregnancy well. The main risks are right-sided heart failure and dysrhythmias. Their volume status should be mon-itored throughout pregnancy and complaints of palpitations or syncope investigated with a Holter or an event monitor. Delivery should include cardiac monitoring (91–94).

Other Repaired Congenital Heart Conditions

An increasing number of women with congenital heart prob-lems that were repaired in childhood are reaching adulthood and undergoing pregnancy. In general, these patients’ course in pregnancy is readily predictable by the parameters out-lined earlier in this chapter. The majority will have a good pregnancy outcome for both themselves and their offspring if they enter the pregnancy with a good functional status (75,95).

Peripartum Cardiomyopathy

The National Heart, Lung, and Blood Institute (NHLBI) defines PPCM as the new onset of systolic dysfunction occur-ring in the absence of other plausible causes anytime between the final month of pregnancy up to 5 months postpartum. The incidence is between 1 in 2,000 to 1 in 15,000 pregnancies, and may be increasing (96–98). Multiparity, twin gestation, maternal age greater than 30 years, presence of preeclampsia/eclampsia and black race are all known to be risk factors, but causality is not yet proven. Precise mechanisms that lead to PPCM remain poorly defined. Many etiologic processes have been suggested (99) including abnormal immune response to pregnancy, maladaptive response to the hemodynamic changes of pregnancy, prolonged tocolysis, increased concentration of inflammatory cytokines, angiogenic imbalance mediated via prolactin and its fragments (100), and possible genetic mecha-nisms, though a specific genetic mutation causally associated with PPCM is yet to be identified. Generally, patients with PPCM have a greater recovery of LV function and a better prognosis than patients with other forms of dilated cardio-myopathy. Most women with PPCM will have complete or at least partial recovery within 6 months of onset while women with depressed LV function beyond 6 months of diagnosis have worse clinical outcomes and higher 5-year mortality rates (101). Mortality can be due to end-stage heart failure, arrhythmia, or thromboembolism.

Pathologic findings include four-chamber enlargement with normal coronary arteries and valves. Light microscopic findings include myocardial hypertrophy and fibrosis with scattered mononuclear infiltrates. Clinical signs include symp-toms of ventricular failure with possible associated dysrhyth-mias and/or pulmonary emboli. Treatment includes bed rest, sodium restriction, diuresis, and preload/afterload reduction with a calcium channel blocker and hydralazine while preg-nant and an angiotensin-converting enzyme inhibitor postpar-tum. Because pregnancy is associated with increased risk of thrombosis, patients with an ejection fraction less than 35% should be considered for anticoagulation with low–molecular-weight heparin (LMWH) while pregnant and warfarin post-partum. Antidysrhythmics should be used in a manner similar to what would be done for any patient with an idiopathic car-diomyopathy. Although the exact risk remains unclear, there is evidence that PPCM may recur or worsen with subsequent pregnancies (102).

Hypertrophic Cardiomyopathy

During pregnancy, the course of hypertrophic cardiomyopa-thy is variable because while the normal increase of blood vol-ume is beneficial, the decrease in systemic vascular resistance and the increase in heart rate may be detrimental. Several large case series have highlighted the risks for these patients during pregnancy (103–106). The risks are inherently greater for those women who are symptomatic before pregnancy or in those with severe left ventricular outflow tract obstruction. Complications are not common, but include congestive heart failure, chest pain, supraventricular tachycardias (SVTs), ventricular tachy-cardia, and sudden death. Complications can occur at any point in the pregnancy or during labor as a result of stress, pain, and increased circulating catecholamines. Moreover, the immedi-ate postpartum period can increase risk due to blood loss and decrease in systemic vascular resistance. Atrial fibrillation and SVTs are a common feature of this cardiac anomaly; thus, cardi-oselective β-blockers and verapamil are usually administered to these patients. Tocolytics, sympathomimetic agents, and digoxin should be avoided in these patients, as they may increase the risk of dysrhythmia. The peripartum period should include car-diac monitoring and use of forceps or vacuum extractor so that the mother has to do little or no pushing. If regional anesthesia is employed, it should be done incrementally and with agents that minimize the risk of a sudden drop in preload.

Ischemic Heart Disease in Pregnancy

Although myocardial infarction in pregnancy is uncommon, with an incidence estimated at between 1 in 10,000 and 1 in 35,700, it does appear to be increasing. Risk factors include advancing age, preeclampsia, multiparity, chronic hypertension, obesity, and diabetes. Myocardial infarctions associated with pregnancy can occur at any time during gestation, with one report find-ing that 38% occurred antepartum, 21% intrapartum, and 41% in the first 6 weeks postpartum. Maternal mortality rate ranges from 7% to 35%, with a disproportionate number of deaths occurring among the antenatal cases (107–109). A large portion of pregnancy-associated myocardial infarctions are not due to atherosclerotic heart disease but instead due to coronary artery in situ thrombus formation, dissection, or spasm.

Diagnosis of ischemic heart disease in pregnancy does require considering it as part of the differential diagnosis, even in the absence of traditional risk factors. Clinicians should also be aware that creatine phosphokinase (CPK) and creatine kinase-MB (CK-MB) can be mildly elevated following a cesar-ean delivery and that troponin is a more specific marker of cardiac disease in the peripartum period. All forms of stress testing can be safely carried out in pregnancy, including nuclear imaging, although many centers prefer exercise echocardiogra-phy for this population. Diagnostic coronary angiography can and should be performed on pregnant women for the same indications as for nonpregnant patients.

Treatment of coronary artery disease remains largely unchanged in pregnancy. None of the medications commonly used to treat ischemic heart disease have been shown to cause adverse effects in the fetus. There is broad experience with low-dose aspirin, nitrates, β-blockers, and heparins in pregnancy. The paucity of data regarding the use of clopidogrel and the platelet glycoprotein IIb/IIIa inhibitors should limit their use in pregnancy to clinical scenarios with proven benefits. Statins

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were previously considered to be teratogenic but a recent sys-tematic review suggests that the doses which are commonly prescribed do not in fact increase any adverse fetal outcomes (110). Coronary angiography, angioplasty and stenting, and thrombolysis have been and can be carried out safely through-out pregnancy (111–114).

The management of laboring patients with ischemic heart disease should be the same for other cardiac patients as dis-cussed in the section above on general principles of manage-ment of cardiac disease at the time of delivery, and has strong parallels with the management of the cardiac patient undergoing general surgery.

Cardiac Dysrhythmias in Pregnancy

Dysrhythmias during gestation, and especially labor and delivery, appear to be more common than in the nonpregnant population (115). Hormonal changes, stress, and anxiety are contributing factors; however, most dysrhythmias are not seri-ous unless they are associated with organic heart disease.

atrial Fibrillation

Atrial fibrillation occurring in pregnancy is usually associated with underlying disease such as MS, peripartum cardiomy-opathy, hypertensive heart disease, thyroid disease, or ASDs. Patients with acute atrial fibrillation and significant hemody-namic changes—such as hypotension or loss of consciousness—require direct current cardioversion. Cardioversion appears to have no adverse effects on the fetus. Most patients, however, will require only medical management with rate-controlling or rhythm-restoring antidysrhythmics. β-Adrenergic blockers such as metoprolol, calcium channel blockers such as diltiazem or verapamil, and agents such as procainamide or digoxin can all be used safely during pregnancy. Amiodarone would not be consid-ered a first-line agent for hemodynamically stable atrial fibrilla-tion because of its possible effects on the fetal thyroid, but its use in pregnancy is not absolutely contraindicated and the risks of potential use must be weighed against the potential benefits and seriousness of the indication. Anticoagulation for atrial fibrilla-tion in pregnancy has the same indications as in nonpregnant patients, but the agent that must be used is heparin— usually in the form of subcutaneous LMWH—because warfarin is associ-ated with adverse fetal effects throughout gestation.

Supraventricular Tachycardia

SVTs during pregnancy can occur with or without organic heart disease. Four percent of women with SVT report that their condition was first identified in pregnancy, and up to 22% state that pregnancy exacerbated their condition (116). In the absence of underlying cardiac disease, these tachycardias are not usually associated with increased morbidity. However, in patients with underlying structural cardiac disease or cardio-myopathy, SVT can lead to heart failure and death. Treatment protocols for SVT remain unchanged in pregnancy and include carotid sinus massage, adenosine, calcium channel blockers, β-blockers, and direct current cardioversion (117,118).

Ventricular Dysrhythmias

Ventricular dysrhythmia during pregnancy may be associ-ated with cocaine use, peripartum or any other form of cardiomyopathy, ischemic heart disease, and digitalis toxicity. Antidysrhythmic agents for which we have the most pregnancy

data are lidocaine, β-blockers, and procainamide. Amiodarone is associated with an increased risk of fetal thyroid disease and, although its use in pregnancy is permissible, it should not be considered a first-line agent. Implantable defibrillators can and should be used when indicated in pregnancy, although they will need to be turned off during surgical procedures that require the use of cautery.

bradycardia

Bradydysrhythmias during pregnancy are rare and may result from infection such as Lyme disease (which can cause heart blocks of varying degrees), hypothyroidism, myocarditis, drug-induced, or congenital or acquired heart blocks. Perma-nent pacemakers are indicated for hemodynamically signifi-cant bradycardia. Patients with pre-existing pacemakers may need to have their baseline rate increased during pregnancy to mimic the normal physiologic changes of pregnancy.

antidysrhythmic Drugs

Table 78.7 classifies the commonly used antidysrhythmic agents on the basis of what is known about their safety in pregnancy. Although there are obviously agents that we know more about than others, it is important to reemphasize here that both mother and fetus benefit from the use of the best agent to control cardiac symptoms in pregnancy, and treat-ment should never be withheld from a pregnant woman based on theoretic fears of fetal harm.

Cardiac Surgery During Pregnancy

As in other semielective nonobstetric surgery during pregnancy, if nonurgent cardiac surgery is necessary, it should ideally take place during the second trimester. Deferring when possible until after the first trimester avoids the period of organogen-esis and the risk of miscarriage. Third-trimester surgery carries the risk of precipitating preterm labor. However, surgery that is important to a patient’s short-term well-being and survival should be done at any point in gestation as required. Coronary artery bypass grafts, valvuloplasties, valvular replacements, and aortic root replacements have all been done in pregnancy with good outcomes for mother and baby. When medical man-agement can ameliorate the disease process, surgery may be postponed until the patient has recovered at least 4 to 6 weeks postpartum; however, such decisions should be based on the best plan of action for the mother’s safety rather than a cultural discomfort related to performing surgery in pregnancy.

Special intraoperative considerations in pregnant patients include fetal monitoring during and after surgery, maintenance of high flow and systemic mean arterial pressure (during car-diopulmonary bypass), and uterine displacement devices if the patient is in the supine position for a median sternotomy. Although the pregnant patient has fared well with open heart procedures, fetal mortality rate can be high. Generally, better results are seen in closed heart procedures. Postoperatively, fetal monitoring should be continued and maternal analgesia maintained to avoid precipitating labor from accelerated post-operative pain.

Pregnancy after Prosthetic Valve Surgery

Patients with mechanical heart valve prostheses pose a sig-nificantly increased risk for thromboembolic events during

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pregnancy. Fewer maternal and fetal complications occur with bioprosthetic valves but the need for reoperation on these valves for degenerative changes means they are not commonly used in women of reproductive age.

Heparin, typically LMWH, is the anticoagulant agent of choice during pregnancy because its molecular weight prevents placental crossover, and it is not teratogenic. It is now well established as the anticoagulant of choice in pregnancy for all indications except for mechanical heart valves. Questions still remain as to whether LMWH provides the same level of protection against mechanical valve thrombosis as warfarin. Although warfarin and its derivatives are associated with an increased risk of central nervous system anomalies and war-farin embryopathy, it may be that the risk is worth taking to prevent the catastrophic consequences of valve thrombosis (119–121). Some experts therefore recommend that women with mechanical heart valves use LMWH during the period of organogenesis, switch to warfarin for the majority of the pregnancy, and then switch back to LMWH close to term to avoid both fetal and maternal bleeding associated with deliv-ery. Other experts would use LMWH but carry out frequent testing of the peak and trough heparin levels—anti-Xa levels—to ensure that the patient is adequately anticoagulated.

Cardiac Transplant Patients

With the increasing number and survival of heart transplant recipients, increasing numbers of women who have under-gone this procedure have become pregnant (122,123). The pregnancy experience with solid tissue transplant patients in general has found a 25% risk of maternal complications (with over half of these complications being hypertension), a 29% risk of miscarriage, and a 41% risk of prematurity (123). The best data specific to cardiac transplantation describe 32 US pregnancies in women who had undergone cardiac transplan-tation, and found a 44% rate of hypertension, a 22% risk of rejection, and a 13% risk of worsening renal function. Neona-tal complications were similar to the data described above for all solid tissue transplants (124). In light of these data, women who have undergone cardiac transplantation are warned of the possible risks of a pregnancy, and are encouraged to wait 2 years after transplantation before becoming pregnant to ensure that the transplant has been a success. Drugs used to prevent rejection should be continued during pregnancy; evi-dence of their safety is accumulating. If antirejection treatment is continued, pregnancy does not appear to increase the risk of rejection (123,124). The peripartum management should be dictated by the quality of left ventricular function in a manner similar to that discussed previously in this chapter.

Cardiopulmonary Resuscitation

Pregnancy poses some unique problems during cardiopulmo-nary resuscitation (CPR). In the third trimester and particu-larly near term, the gravid uterus impairs venous return. Thus, during CPR, the uterus should be displaced (i.e., left uterine tilt). Moreover, if defibrillation is required, the left breast needs to be displaced because of marked enlargement during pregnancy. The unlikely but theoretical possibility that there may be electrical arcing between a defibrillator and any fetal monitoring devices means that fetal monitoring devices should be removed prior to defibrillation. Otherwise, the Advanced

Cardiac Life Support (ACLS) protocols, including medications and the use of the defibrillator, should be followed as done in a nonpregnant patient. Some experts would suggest that the use of amiodarone should be deferred in cardiac resuscitation until alternative appropriate agents have failed. However, in the context of a cardiac arrest, the authors would support the use of any recommended ACLS medication, as the one-time use of any of these agents is very unlikely to be of any harm, and may be of great benefit to both mother and fetus.

Data about the risk and benefits of an emergency cesarean delivery in the context of maternal resuscitation are very lim-ited. The present-day view is that if the fetus has reached a point in the pregnancy where survival after delivery is possible (typically more than 24 weeks of gestation), emergency cesar-ean should be considered a part of the resuscitative efforts. Evacuation of the gravid uterus, with the concomitant release of pressure on the inferior vena cava and removal of the low-resistance circulatory unit that is the placenta, may improve the efficacy of chest compressions and improve the outcome for both mother and baby. Present recommendations are for con-sideration of cesarean delivery in pregnant women greater than 24 of weeks gestation who have had a cardiac arrest and failed to respond to 4 minutes of aggressive and appropriate resusci-tative efforts (125). Consensus statements have been published by both the American Heart Association (126) and Society of Obstetric Anesthesia and Perinatology (127) on this topic.

• Preeclampsia complicates 5% to 8% of all pregnancies, can occur at any time in the second half of pregnancy and the postpartum period, and is related to placental insufficiency.

• The following are all life-threatening maternal compli-cations of preeclampsia: severe hypertension, eclamptic seizures, cerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation, acute renal failure, hepatic failure and/or rupture, and diabetes insipidus.

• A particularly severe form of preeclampsia is the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet counts).

• Magnesium sulfate is the drug of choice to prevent eclamptic seizures, but careful monitoring for toxicity (hypotension, muscular weakness, respiratory depres-sion) is important particularly in patients with worsen-ing renal dysfunction.

• Cardiac disease during pregnancy has an incidence rate of 0.4% to 4%, and is now the leading cause of mater-nal mortality in the developed world.

• Factors associated with an increased risk of cardiac complications in pregnancy are: premorbid New York Heart Association (NYHA) functional class III or IV status, cyanosis, presence of pulmonary hypertension, left-sided obstructive cardiac lesions, left ventricu-lar systolic dysfunction, prior cardiac events and/or previous arrhythmias.

• Three periods of particular risks are: end of second tri-mester, time of labor and delivery, immediate postpar-tum period (first 72 hours).

Key Points

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References 1. Roberts JM, August PA, Bakris G, et al. Hypertension in pregnancy. Report

of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122–1131.

2. Powrie RO. A 30-year-old woman with chronic hypertension trying to conceive. JAMA. 2007;298(13):1548–1558.

3. Soubra SH, Guntupalli KK. Critical illness in pregnancy: an overview. Crit Care Med. 2005;33:S248–S255.

4. Sibai B, Dekker G, Kupferminc M. Preeclampsia. Lancet. 2005;365(9461): 785–799.

5. ACOG Committee on Practice Bulletins-Obstetrics. ACOG practice bul-letin: diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol. 2002;99(1):159–167.

6. Bletka M, Hlavatj V, Tenkova M, et al. Volume of whole blood and abso-lute amount of serum proteins in the early stages of late toxemia of preg-nancy. Am J Obstet Gynecol. 1970;106:10.

7. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728):1592–1594.

8. Lain KY, Roberts JM. Contemporary concepts of the pathogenesis and management of pre-eclampsia. JAMA. 2002;287:3183–3186.

9. Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating anti-angiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005.

10. Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–683.

11. Levine RJ, Thadhani R, Qian C, et al. Urinary placental growth factor and risk of preeclampsia. JAMA. 2005;293(1):77–85.

12. Powrie RO, Miller MA. Hypertension in pregnancy. In: Rosene-Montella K, Lee R, Keely EJ, et al., eds. Medical Care of the Pregnant Patient. Phila-delphia, PA: American College of Physicians; 2007:153–162.

13. Natarajan P, Shennan AH, Penny J, et al. Comparison of auscultatory and oscillometric automated blood pressure monitors in the setting of pre-eclampsia. Am J Obstet Gynecol. 1999;181(5 Pt 1):1203–1210.

14. von Dadelszen P, Magee LA, Devarakonda RM, et al. The prediction of adverse maternal outcomes in preeclampsia. J Obstet Gynaecol Can. 2004; 26(10):871–879.

15. Lam C, Lim KH, Kang DH, et al. Uric acid and preeclampsia. Semin Nephrol. 2005;25(1):56–60.

16. Rodriguez-Thompson D, Lieberman ES. Use of a random urinary protein-to-creatinine ratio for the diagnosis of significant proteinuria during preg-nancy. Am J Obstet Gynecol. 2001;185(4):808–811.

17. Durwald C, Mercer B. A prospective comparison of total protein/creat-inine ratio versus 24-hour urine protein in women with suspected pre-eclampsia. Am J Obstet Gynecol. 2003;189(3):848–852.

18. Martin JN Jr, Thigpen BD, Moore RC, et al. Stroke and severe preeclamp-sia and eclampsia: a paradigm shift focusing on systolic blood pressure. Obstet Gynecol. 2005;105:246–254.

19. Committee on Obstetric Practice. Committee opinion No. 514: emergent therapy for acute-onset, severe hypertension with preeclampsia or eclamp-sia. Obstet Gynecol. 2011;118:1465–1468.

20. Magee LA, Cham C, Waterman EJ, et al. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003;327(7421):955–960.

21. Magee LA, Miremadi S, Li J, et al. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with preeclampsia. Am J Obstet Gynecol. 2005;193(1):153–163.

22. Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005;105(2):402–410.

23. Duley L. Evidence and practice: the magnesium sulphate story. Best Pract Res Clin Obstet Gynaecol. 2005;19(1):57–74.

24. Jeng JS, Tang SC, Yip PK. Stroke in women of reproductive age: com-parison between stroke related and unrelated to pregnancy. J Neurol Sci. 2004;221(1–2):25–29.

25. Engelhardt T, MacLennan FM. Fluid management in preeclampsia. Int J Obstet Anesth. 1999;8(4):253–259.

26. Sibai BM, Mabie BC, Harvey CJ, et al. Pulmonary edema in severe pre-eclampsia-eclampsia: analysis of thirty-seven consecutive cases. Am J Obstet Gynecol. 1987;156(5):1174–1179.

27. Bandi VD, Munnur U, Matthay MA. Acute lung injury and acute respira-tory distress syndrome in pregnancy. Crit Care Clin. 2004;20(4):577–607.

28. Powrie RO, Levy M. Pulmonary edema in pregnancy. In: Rosene-Montella K, Lee R, Keely EJ, et al, eds. Medical Care of the Pregnant Patient. Phila-delphia, PA: American College of Physicians; 2007:383–394.

29. Letsky EA. Disseminated intravascular coagulation. Best Pract Res Clin Obstet Gynaecol. 2001;15(4):623–644.

30. Kramer RL, Izquierdo LA, Gilson GJ, et al. Preeclamptic labs for evaluat-ing hypertension in pregnancy. J Reprod Med. 1997;42:223–228.

31. Gammil HS, Jeyabalan A. Acute renal failure in pregnancy. Crit Care Med. 2005;33(10 Suppl):S372–S384.

32. Dotsch J, Hohmann M, Kuhl PG. Neonatal morbidity and mortality asso-ciated with maternal hemolysis elevated liver enzymes and low platelets syndrome. Eur J Pediatr. 1997;156:389–391.

33. Baxter JK, Weinstein L. HELLP syndrome: the state of the art. Obstet Gynecol Surv. 2004;59(12):838–845.

34. van Runnard Heimel PJ, Franx A, Schobben AF. Corticosteroids, pregnancy, and HELLP syndrome a review. Obstet Gynecol Surv. 2005;60(1):57–70.

35. Katz L, de Amorim MM, Figueiroa JN, et al. Postpartum dexametha-sone for women with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: a double-blind, placebo-controlled, randomized clini-cal trial. Am J Obstet Gynecol. 2008;198(3):283.e1–283.e8.

36. Sheikh RA, Yasmeen S, Pauly MP, et al. Spontaneous intrahepatic hem-orrhage and hepatic rupture in the HELLP syndrome: four cases and a review. J Clin Gastroenterol. 1999;28(4):323–328.

37. Kalelioglu I, Kubat Uzum A, Yildirim A, et al. Transient gestational diabetes insipidus diagnosed in successive pregnancies: review of patho-physiology, diagnosis, treatment, and management of delivery. Pituitary. 2007;10(1):87–93.

38. Strauss RG, Keefer JR, Burke T, et al. Hemodynamic monitoring of car-diogenic pulmonary edema complicating toxemia of pregnancy. Obstet Gynecol. 1980;55:170–174.

39. Benedetti TJ, Cotton DB, Read JC, et al. Hemodynamic observations in severe preeclampsia with a flow-directed pulmonary artery catheter. Am J Obstet Gynecol. 1980;136:465–470.

40. Young P, Johanson R. Haemodynamic, invasive and echocardiographic monitoring in the hypertensive parturient. Best Pract Res Clin Obstet Gynaecol. 2001;15(4):605–622.

41. Fujitani S, Baldisseri MR. Hemodynamic assessment in a pregnant and peripartum patient. Crit Care Med. 2005;33(10 Suppl):S354–S361.

42. Gilbert WM, Towner DR, Field NT, Anthony J. The safety and utility of pulmonary artery catheterization in severe preeclampsia and eclampsia. Am J Obstet Gynecol. 2000;182(6):1397–1403.

43. Young PF, Leighton NA, Jones PW, et al. Fluid management in severe pre-eclampsia (VESPA): Survey of members of ISSHP. Hypertens Pregnancy. 2000;19(3):249–259.

• Among the more commonly used cardiac medications, only angiotensin-converting enzyme inhibitors, angio-tensin receptor blockers, and warfarin are absolutely contraindicated in pregnancy.

• The radiation exposure associated with all plain film radiographs, CT scans, nuclear scans, and angiography are all well below what is deemed acceptable during pregnancy. None of the contrast agents used have been associated with any fetal complications.

• For most cardiac patients, it is recommended that a multidisciplinary patient care conference be assembled well in advance of the anticipated time of delivery.

• The need for cesarean deliveries is generally dictated by obstetric concerns, and vaginal deliveries should gener-ally be viewed as the safest and best options for cardiac patients.

• For either mode of delivery, early establishment of regional anesthesia is recommended to reduce the unde-sired effects of labor on heart rate (tachycardia) and blood pressure (increased systemic vascular resistance).

• PPCM is defined as the new onset of systolic dysfunc-tion occurring in the absence of other plausible causes anytime between the final month of pregnancy up to 5 months postpartum.

• Emergency cesarean delivery should be strongly consid-ered in pregnant women beyond 24 weeks of gestation who have had a cardiac arrest and failed to respond to 4 minutes of aggressive and appropriate resuscitative efforts.

LWBK1580_C78_p906-926.indd 924 29/07/17 11:30 AM


44. Elkayam U, Gleicher N. Cardiac Problems in Pregnancy: Diagnosis and Management of Maternal and Fetal Heart Disease. New York: Wiley-Liss; 1998.

45. Berg CJ, Callaghan WM, Syverson C, Henderson Z. Pregnancy-related mortality in the United States, 1998 to 2005. Obstet Gynecol. 2010;116:1302–1309.

46. James CF, Banner T, Levelle JP, et al. Noninvasive determination of cardiac output throughout pregnancy. Anesthesiology. 1985;63(Suppl 3A):A434.

47. Hunter S, Robson SC. Adaptation of the maternal heart in pregnancy. Br Heart J. 1992;68:540–543.

48. Robson SC, Dunlop W, Boys RJ, et al. Cardiac output during labour. BMJ. 1987;295:1169–1172.

49. Capeless EL, Clapp JF. When do cardiovascular parameters return to their preconception values? Am J Obstet Gynecol. 1991;165:883–886.

50. Clark SL, Cotton DG, Lee W, et al. Central hemodynamic assessment. Am J Obstet Gynecol. 1989;161:1439–1442.

51. Munnur U, de Boisblanc B, Suresh MS. Airway problems in pregnancy. Crit Care Med. 2005;33(10 Suppl):S259–S268.

52. Ueland K, Hansen JM. Maternal cardiovascular dynamics. II, Posture and uterine contractions. Am J Obstet Gynecol. 1969;103(1):1–7.

53. Gogarten W. Spinal anaesthesia for obstetrics. Best Pract Res Clin Anaes-thesiol. 2003;17(3):377–392.

54. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of preg-nancy outcomes in women with heart disease. Circulation. 2001;104:515–521.

55. Pradhan M, Manisha M, Singh R, et al. Amiodarone in treatment of fetal supraventricular tachycardia: a case report and review of literature. Fetal Diagn Ther. 2006;21(1):72–76.

56. Lomenick JP, Jackson WA, Backeljauw PF. Amiodarone-induced neonatal hypothyroidism: a unique form of transient early-onset hypothyroidism. J Perinatol. 2004;24(6):397–399.

57. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354(23):2443–2451.

58. Schaefer C, Hannemann D, Meister R, et al. Vitamin K antagonists and pregnancy outcome: a multi-centre prospective study. Thromb Haemost. 2006;95(6):940–957.

59. Briggs GG, Freeman RK. Drugs in Pregnancy and Lactation. 10th ed. Philadelphia, PA: Wolters Kluwer; 2014.

60. Shepard TH, Lemire RS. Shepard’s Catalog of Teratogenic Agents. 13th ed. Baltimore, MD: Johns Hopkins University Press; 2010.

61. Coustan DR, Michizuki TK. Handbook for Prescribing Medications in Pregnancy. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998.

62. Friedman JM, Polifka JE. Teratogenic Effects of Drugs: A Resource for Clinicians. 2nd ed. Baltimore, MD: Johns Hopkins University Press; 2000.

63. Hale TW, Rowe HE. Medications and Mothers’ Milk: A Manual of Lacta-tional Pharmacology. 16th ed. Plano, TX: Hale Publishing; 2014.

64. Reprotox website. www.REPROTOX.org. 65. TERIS: clinical teratology web. University of Washington website. http://

depts.washington.edu/∼terisweb/teris/. 66. Patel SJ, Reede DL, Katz DS, et al. Imaging the pregnant patient for non-

obstetric conditions: algorithms and radiation dose considerations. Radio-graphics. 2007;27(6):1705–1722.

67. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endo-carditis: guidelines from the American Heart Association. Circulation. 2007;116:1736–1754.

68. Hameed A, Karaalp IS, Tummala PP, et al. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol. 2001;37:893–899.

69. Silversides CK, Colman JM, Sermer M, et al. Cardiac risk in pregnant women with rheumatic mitral stenosis. Am J Cardiol. 2003;91:1382–1385.

70. al Kasab SM, Sabag T, al Zaibag M, et al. Beta-adrenergic receptor block-ade in the management of pregnant women with mitral stenosis. Am J Obstet Gynecol. 1990;163:37–40.

71. Esteves CA, Ramos AL, Braga SL. Effectiveness of percutaneous balloon mitral valvotomy during pregnancy. Am J Cardiol. 1991;68:930–934.

72. de Souza JAM, Martinez EE, Ambrose JA, et al. Percutaneous balloon mitral valvuloplasty in comparison with open mitral valve commissurot-omy for mitral stenosis during pregnancy. J Am Coll Cardiol. 2001;37:900.

73. Sullivan HJ. Valvular heart surgery during pregnancy. Surg Clin North Am. 1995;75:59–75.

74. Oakley C, Child A, Jung B. Expert consensus document on management of cardiovascular disease during pregnancy. Eur Heart J. 2003;24:761.

75. Elkayam U, Bitar F. Valvular heart disease and pregnancy. J Am Coll Car-diol. 2005;46:223–230.

76. Silversides CK, Colman JM, Sermer M, et al. Early and intermediate-term outcomes of pregnancy with congenital aortic stenosis. Am J Cardiol. 2003;91(11):1386–1389.

77. Tzemos N, Silversides CK, Colman JM, et al. Late cardiac outcomes after pregnancy in women with congenital aortic stenosis. Am Heart J 2009;157(3):474–480.

78. Easterling TR, Chadwick HS, Otto CM, et al. Aortic stenosis in preg-nancy. Obstet Gynecol. 1988;72:113–118.

79. Graham TP. Ventricular performance in adults after operation for congeni-tal heart disease. Am J Cardiol. 1982;50:612–620.

80. Gleicher N, Midwall J, Hochberger D, et al. Eisenmenger’s syndrome and pregnancy. Obstet Gynecol Surv. 1979;34:721–741.

81. Avila WS, Grinberg M, Snitcowsky R, et al. Maternal and fetal outcome in preg-nant women with Eisenmenger’s syndrome. Eur Heart J. 1995;16:460–464.

82. Yentis SM, Steer PJ, Plaat F. Eisenmenger’s syndrome in pregnancy; maternal and fetal mortality in the 1990s. Br J Obstet Gynaecol. 1998;105:921–922.

83. Elkayam U, Ostzega A, Shotan A, et al. Cardiovascular problems in pregnant women with the Marfan syndrome. Ann Intern Med. 1995;123:117–122.

84. Lipscomb KJ, Smith JC, Clarke B, et al. Outcome of pregnancy in women with Marfan’s syndrome. BJOG. 1997;104:201–206.

85. Lind J, Wallenburg HC. The Marfan syndrome and pregnancy: a retro-spective study in a Dutch population. Eur J Obstet Gynecol Reprod Biol. 2001;98:28–35.

86. Rossiter JP, Repke JT, Morales AJ, et al. A prospective longitudinal evaluation of pregnancy in the Marfan syndrome. Am J Obstet Gynecol. 1995;173:1599–1606.

87. Carabello BA, Chatterjee K, de Leon AC, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. J Am Coll Cardiol. 2006;48(3):e1–e148.

88. Beauchesne LM, Connolly HM, Ammash NM, et al. Coarctation of the aorta; outcome of pregnancy. J Am Coll Cardiol. 2001;38(6):1728–1733.

89. Vriend JW, Drenthen W, Pieper PG, et al. Outcome in pregnancy in patients after repair of aortic coarctation. Eur Heart J. 2005;26(20):2173–2178.

90. Fishburne JI Jr, Dormer KJ, Payne GG, et al. Effects of amrinone and dopamine on uterine blood flow and vascular responses in the gravid baboon. Am J Obstet Gynecol. 1988;158:829–837.

91. Meijer JM, Pieper PG, Drenthen W, et al. Pregnancy, fertility and recur-rence risk in corrected Tetralogy of Fallot. Heart. 2005;91:801–805.

92. Singh H, Bolton PJ, Oakley CM. Pregnancy after surgical correction of tetralogy of Fallot. BMJ. 1982;285:168–170.

93. Presbitero P, Somerville J, Stone S, et al. Pregnancy in cyanotic congenital heart disease: outcome of mother and fetus. Circulation. 1994;89:2673–2676.

94. Patton DE, Lee W, Cotton DB, et al. Cyanotic maternal heart disease in pregnancy. Obstet Gynecol Surv. 1990;45:594–600.

95. Nunley WC, Kolp LA, Dabinett LN, et al. Subsequent fertility in women who undergo cardiac surgery. Am J Obstet Gynecol. 1989;161:573–576.

96. Bernstein PS, Magriples U. Cardiomyopathy in pregnancy: a retrospective study. Am J Perinatol. 2001;18:163–168.

97. Gunderson EP, Croen LA, Chiang V, et al. Epidemiology of peripartum cardiomyopathy: incidence, predictors, and outcomes. Obstet Gynecol. 2011;118(3):583–591.

98. Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet. 2006; 368(9536):687–693.

99. Johnson-Coyle L, Jensen L, Sobey A. Peripartum cardiomyopathy. Am J Crit Care. 2012;21(2):89–98.

100. Hilfiker-Kleiner D, Sliwa K. Pathophysiology and epidemiology of peripar-tum cardiomyopathy. Nature Rev Cardiol. 2014;11:364–370.

101. Elkayam U. Clinical characteristics of peripartum cardiomyopathy in the United States: diagnosis, prognosis, and management. J Am Col Cardiol. 2011;58(7):659–670.

102. Elkayam U, Tummala PP, Rao K. Maternal and fetal outcomes of subse-quent pregnancies in women with peripartum cardiomyopathy. N Engl J Med. 2001;344(21):1567–1571.

103. Autore C, Conte MR, Piccininno M, et al. Risk associated with pregnancy in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002;40:1864–1869.

104. Thaman R, Varnava A, Hamid MS, et al. Pregnancy related complications in women with hypertrophic cardiomyopathy. Heart. 2003;89:752–756.

105. Wigle ED, Rakowski H, Kimball BP, et al. Hypertrophic cardiomyopathy: clinical spectrum and treatment. Circulation. 1995;92:1680–1692.

106. Avila WS, Amaral FM, Ramires JA, et al. Influence of pregnancy on clini-cal course and fetal outcome of women with hypertrophic cardiomyopa-thy. Arq Bras Cardiol. 2007;88:423–428.

107. James AH, Jamison MG, Biswas MS, et al. Acute myocardial infarc-tion in pregnancy: a United States population-based study. Circulation. 2006;113:1564–1571.

LWBK1580_C78_p906-926.indd 925 29/07/17 11:30 AM


108. Badin E, Enciso R. Acute myocardial infarction during pregnancy and puerperium: a review. Angiology. 1996;47:739–756.

109. Ladner HE, Danielsen B, Gilbert WM. Acute myocardial infarction in pregnancy and the puerperium: a population-based study. Obstet Gyne-col. 2005;105:480–484.

110. Kusters DM, Hassani Lahsinoui H, van de Post JA, et al. Statin use in pregnancy: a systematic review & meta-analysis. Expert Rev Cardiovasc Ther. 2012;10(3):363–378.

111. Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol Surv. 1995;50:534–541.

112. Cowan NC, deBelder MA, Rothman MT. Coronary angioplasty in preg-nancy. Br Heart J. 1988;59:588–592.

113. Giudici MC, Artis AK, Webel RR, et al. Postpartum myocardial infarction treated with balloon coronary angioplasty. Am Heart J. 1989;118:614.

114. Saxena R, Nolan TE, von Dohlen T, et al. Postpartum myocardial infarc-tion treated by balloon coronary angioplasty. Obstet Gynecol. 1992;79: 810–811.

115. Shotan A, Ostrzega E, Mehra A, et al. Incidence of arrhythmias in normal pregnancy and relation to palpitations, dizziness, and syncope. Am J Car-diol. 1997;79:1061–1064.

116. Lee SH, Chen SA, Chiang CE, et al. Effects of pregnancy on first onset and symptoms of paroxysmal supraventricular tachycardia. Am J Cardiol. 1995;76:675–678.

117. Tawan M, Levine J, Mendelson M, et al. Effect of pregnancy on paroxys-mal supraventricular tachycardia. Am J Cardiol. 1993;72:838.

118. Silversides CK, Harris L, Haberer K, et al. Recurrence rates of arrhythmias during pregnancy in women with previous tachyarrhythmia and impact on fetal and neonatal outcomes. Am J Cardiol. 2006;97:1206–1212.

119. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000;160:191–196.

120. Maxwell CV, Poppas A, Dunn E, et al. Pregnancy, mechanical heart valves and anticoagulation: navigating the complexities of management during gestation. In: Rosene-Montella K, Keely EJ, Lee RV, et al., eds. Medical Care of the Pregnant Patient. 2nd ed. Philadelphia, PA: American College of Physicians; 2007:344–355.

121. Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. (Writing Committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease). Developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation. 2006;114(5):e84–e231.

122. Miniero R, Tardivo I, Curtoni ES, et al. Outcome of pregnancy after organ transplantation: a retrospective survey in Italy. Transplant Int. 2005;17:724.

123. Wagoner L, Taylor D, Olson S, et al. Immunosuppressive therapy, man-agement and outcomes of heart transplant recipients during pregnancy. J Heart Lung Transplant. 1993;12:993.

124. Branch KR, Wagoner LE, McGrory CH, et al. Risk of subsequent pregnan-cies on mother and newborn in female heart transplant recipients. J Heart Lung Transplant. 1998;17:698.

125. Hui D, Morrison LJ, Windrim R, et al. The American Heart Association 2010 guidelines for the management of cardiac arrest in pregnancy: con-sensus recommendations on implementation strategies. J Obstet Gynaecol Can. 2011;33:858–863.

126. Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12. Cardiac arrest in special situations. 2010 American Heart Association Guidelines for Car-diopulmonary Resuscitation and Emergency Cardiovascular Care. Circu-lation. 2010;122:S829–S861.

127. Lipman S, Cohen S, Einav S, et al. The Society for Obstetric Anesthe-sia and Perinatology Consensus Statement on the management of cardiac arrest in pregnancy. Anesth Analg. 2014;118(5):1003–1016.

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