Functional echocardiography in the fetus with non cardiac disease

REVIEW

Functional echocardiography in the fetus with non-cardiac diseaseTim Van Mieghem1*, Ryan Hodges1, Edgar Jaeggi2 and Greg Ryan1

1Fetal Medicine Unit, Mount Sinai Hospital, University of Toronto, Toronto, Canada2Fetal Cardiac Program, Pediatric Cardiology, Hospital for Sick Children, University of Toronto, Toronto, Canada*Correspondence to: Tim Van Mieghem. E-mail: [email protected]

ABSTRACTWe describe the hemodynamic changes observed in fetuses with extra cardiac conditions such as intrauterine growthrestriction, tumors, twin–twin transfusion syndrome, congenital infections, and in fetuses of mothers with diabetes. Inmost fetuses with mild extra cardiac disease, the alterations in fetal cardiac function remain subclinical. Cardiacfunction assessment has however helped us to achieve a better understanding of the pathophysiology of thesediseases. In fetuses at the more severe end of the disease spectrum, functional echocardiography may help in guidingclinical decision-making regarding the need for either delivery or fetal therapy.

The growth-restricted fetus represents a special indication for routine cardiac function assessment, as in uterohemodynamic changes may help optimize the timing of delivery. Moreover, in intrauterine growth restriction, thealtered hemodynamics causes cardiovascular remodeling, which can result in an increased risk of postnatalcardiovascular disease. © 2013 John Wiley & Sons, Ltd.

Funding sources: NoneConflicts of interest: None declared

INTRODUCTIONFetal cardiac function is routinely examined in the contextof congenital heart disease. More recently, functionalechocardiography has also been applied to fetuses with astructurally normal heart and hemodynamic challenges dueto extra cardiac conditions. This experience has providednovel insights into fetal cardiac adaptation to a range ofdifferent fetal and maternal pathologies. Furthermore, novelimaging tools to assess disease progression, prognosis and fetalwell-being have been proposed. The aim of this manuscript is(1) to review the literature regarding the more commonpathologies seen in clinical practice (Table 1) and (2) todemonstrate how functional echocardiography can help guideclinical management decisions of some of these conditions.

BASIC FETAL CARDIOVASCULAR PHYSIOLOGYIn a healthy fetus, oxygenated blood returns from the placentathrough the umbilical vein and the ductus venosus to the rightatrium. The ductus venosus streams this blood preferentiallythrough the foramen ovale toward the left atrium, where itmixes with the pulmonary venous return,1 and the leftventricle then ejects this blood into the aorta. A smallpercentage of the left ventricular output is distributed to thecoronary arteries to perfuse the heart, whereas three quartersof the blood flows to the head and upper body. The remainderof the oxygenated blood is directed into the descending aortaand the lower body.

The right ventricle on the other hand receives lowersaturated blood from the systemic veins, which is forwardedinto the main pulmonary artery. About one third of the rightventricular stroke volume passes via the lung circulation,whereas two thirds advances via the ductus arteriosus intothe descending aorta, the lower body, and the placenta.2

It is important to note that the left and right heartcirculations work in parallel and are connected at the level ofthe foramen ovale, the ductus arteriosus and the aorticisthmus. Although the cardiac chambers appear symmetricalin size, the right ventricle is dominant in a healthy fetus andprovides about 60% of the combined fetal cardiac output,whereas the left ventricle contributes about 40%.3 Functionalor anatomic changes that may occur at the level of thesecommunications allow the fetus to favor one part of thecirculation over another. The change in cardiac loading maythen lead to a discrepancy in ventricular dimensions.

HOW TOASSESS FETAL CIRCULATIONWITH ULTRASOUND?Multiple non-invasive, ultrasound-based, methods are availableto assess the fetal circulation. Here, we will describe the basictools required to understand the hemodynamic changes thatoccur in fetuses with extra cardiac disease. We direct theinterested reader to recent review articles4,5 for a more in-depth discussion of the different indices of cardiac functionand their specific application in individual pathologies. It isimportant to appreciate that most methods described are

Prenatal Diagnosis 2014, 34, 23–32 © 2013 John Wiley & Sons, Ltd.

DOI: 10.1002/pd.4254

Table1

Summaryof

prenatal

andlong

-term

cardiacfind

ings

infetuseswith

non-cardiacdisease

Cardiac

output

Cardiac

size

Hyp

ertro

phy

Diasto

licfunctio

nSy

stolic

functio

nArrhythmia

Long

-term

conseq

uences

IUGR

Normal,shift

towardLV

Relativeca

rdiomeg

aly

RV,late

RVdy

sfunction

(increa

sedafterlo

ad)

Normal

—Globu

larh

eart,

impa

ired

relaxationan

dhype

rtension

SCTan

dTRAP

Increa

sed

Cardiom

egaly

——

Increa

sed

—Normalizationafterresection

CCAM

Decreased

Decreased

—Po

orfillin

gdu

eto

extrinsic

compressio

nNormal

—Normalizationafterresection

Left-sid

edCDH

Normal,shift

towardRV

SmallLV

——

Normal

—Normal

afterC

DH

repa

ir

TTTS

(recipient)

Normal/

decrea

sed

Cardiom

egaly

RV>LV

Intrinsic

RVdy

sfunction>LV

dysfu

nction

Decreased

,late

—Fullreco

very

afterfetosco

piclasera

ndhigh

erarteria

lstiffnessin

dono

raftera

mniod

rainag

e

Fetala

nemia

Increa

sed

Cardiom

egaly

—Normal

Increa

sed

—Pa

rtial

corre

ctionaftertransfusio

n,yetred

uced

LVmassin

childho

od

Pelvicmasses

Normal

Normal/increa

sedif

pulmon

aryhypo

plasia

RVRV

dysfu

nctiondu

eto

increa

sedafterlo

adNormal

—?

Materna

lGravesdisease

Increa

sed

Normal

RVNormal

Normal

Sinustachycardia

Normalizationpo

stnatally

Materna

ldiabe

tes

Normal

Cardiom

egaly

Interventricularsep

tum>

freewall,RV

=LV

Decreased

Decreased

(mild)

—Normalizationpo

stnatally

Myoca

rditis

(SLE,infections)

Normal/

decrea

sed

Cardiom

egaly

—Va

riable

Decreased

Hea

rtbloc

kDilatedca

rdiomyopa

thy

IUGR,

intra

uterinegrow

threstriction;

LV,leftventricle;

RV,rightventricular;S

CT,

sacroc

occyge

alteratoma;

TRAP,

twinreversed

arteria

lperfusio

n;CCAM,c

onge

nitalcystic

adenom

atoidmalformation;

CDH,c

onge

nitald

iaph

ragm

atichernia;T

TTS,

twin–twin

transfusio

nsynd

rome;

SLE,

syste

mic

lupu

serythematosus.

T. V. Mieghem et al.24


indirect reflections of fetal cardiac function and that they arestrongly influenced by cardiac preload (venous return) andafterload (peripheral vascular resistance). Moreover, mostmethods are subject to large inter-observer and intra-observervariability, which, although acceptable in a research setting,limits application in clinical practice.

Cardiac output measurements reflect the volume of bloodflowing through the heart per unit of time. When measuredusing Doppler ultrasound of the outflow valves, combinedleft and right ventricular outputs per fetal weight stay stablethroughout gestation at around 400–450ml/kg/min6,7

Cardiac output is a crude estimate of the cardiac global‘pump’ function and is influenced by heart rate, preload,afterload, ventricular volume, and myocardial contractility.

Methods that look more specifically at myocardial functioninclude the measurement of the shortening fraction8 (thepercentage of radial narrowing of the ventricle during systolemeasured using M-mode echocardiography, which rangesaround 32 ± 6%) or cardiac strain and strain rate (the relativemyocardial shortening over time, which can be measuredusing speckle tracking or tissue Doppler9). Longitudinalventricular contractility can be assessed by evaluating theatrioventricular annulus motion (tricuspid or mitral annularplane systolic excursion10,11). Eyeballing ventricularcontractility, albeit less objective, is a valid clinical tool andcommonly used. Although the aforementioned methods aremore reflective of intrinsic myocardial function, they are stillinfluenced by preload and afterload.

Another commonly used tool in fetal cardiology is themyocardial performance index (MPI) or Tei index,12 whichis the sum of the isovolumetric contraction and relaxationtime (ICT + IRT) divided by the ejection time (Figure 1).These time intervals, during which the heart contracts toovercome the systemic pressure or relaxes in preparationfor ventricular filling, can be measured using eithercombined Doppler sampling of blood flow through theatrioventricular and the outflow valves (Figures 1 and 2) orusing tissue Doppler. The ICT reflects systolic function(contraction), with longer contraction times reflectingworse function. The IRT on the other hand reflects diastolic

myocardial function (relaxation). As such, the complete MPI isa measure of global systolic and diastolic cardiac function,which is strongly dependent on intrinsic myocardial function.

Finally, the E/A index is the ratio of early (E, passiveventricular filling) and late (A, atrial contraction) ventricularinflow through the atrioventricular valves. In the fetus, theE/A index is typically less than 1, and the normal inflowpattern is ‘biphasic’ (Figures 1 and 2) with distinct E and Apeaks. In fetuses with diastolic myocardial dysfunction inwhom the heart becomes less compliant and more dependenton atrial contraction for ventricular filling, the E/A indexdecreases. The E and A waves can also fuse, resulting in a‘monophasic’ inflow pattern. With worsening diastolicfunction, the inflow duration, which usually makes up >35%of the total cardiac cycle length,13 will shorten. Pooratrioventricular valve function can also result in valvularregurgitation, which can be documented with color or pulsedDoppler. Mitral or tricuspid valve regurgitation can either bedue to intrinsic valve abnormalities or can arise as aconsequence of dilatation of the atrioventricular valve ringsecondary to increased volume loading, myocardialdysfunction, or high ventricular pressures.

In most situations, the cardiac sonographer will combinedifferent indices to assess the different aspects ofventricular function or select a particular parameter, whichis most for a specific disease process, as will be discussedlater.

INTRAUTERINE GROWTH RESTRICTION (IUGR)The fetus with progressive placental dysfunction and ensuingIUGR is probably the most comprehensively studied to datefrom a cardiovascular perspective, and this clinical scenario isone of the most common indications for fetal hemodynamicassessment. With advancing placental disease, the resistancein the umbilical artery rises, reflecting a reduction in patentdownstream villous vessels. This can be imaged by Dopplerultrasound, initially as a decrease in end-diastolic velocity,which then progresses to absent and eventually reverseddiastolic flow. The increased placental resistance (afterload)leads to a lower portion of the fetal cardiac output being

Figure 1 Graphical representation of the Doppler waveform used to measure the myocardial performance index. This waveform is obtainedby placing the Doppler sample volume over the mitral and aortic valve together in an apical or basal five-chamber view

Fetal hemodynamics in non-cardiac disease 25


directed to the placenta14 and hence a decreased returnthrough the umbilical vein. Overall however, cardiac outputis maintained because of an increased recirculation withinthe fetal body.14

Fetal hypoxia causes an increase in sympathetic toneand constriction of the portal hepatic vascular bed. Thisconstriction is more pronounced in the portal vessels thanin the ductus venosus and hence favors ductus venosusshunting at the cost of decreased liver perfusion.15

This effect is further augmented by a dilatation of theductus venosus.16 As outlined earlier, the ductus venosuspreferentially directs blood through the foramen ovaletoward the left ventricle. The changes in hepatic andductus venosus blood flow observed in IUGR thereforefavor the left rather than the right ventricular venousreturn.17

The left ventricular output is further augmented bycerebral18 and coronary vasodilatation19 (heart and brainsparing effect), which decrease the left ventricularafterload. The biologic utility of this dominant left-sidedcirculation is that the oxygenated blood from theplacenta is now preferentially shunted toward the heartand brain, which are essential for survival andmetabolically the most demanding. The heart and brainsparing effect is clinically expressed as an increased headcircumference relative to the abdominal circumferenceand a relative cardiomegaly in severe IUGR (normallygrown heart in a small chest).

Despite this protective redistribution of oxygenated bloodtoward the heart, subclinical myocardial impairment occursas demonstrated by an abnormal MPI antenatally and evidenceof myocardial cell damage at delivery.20 Moreover, the fetalheart remodels to a more globular configuration,21 theimplications of which will be discussed later. Of clinicalrelevance, an abnormal MPI seems to predate decompensationor fetal death by 26days.22

As placental resistance increases, and now with a vasodilatedleft-sided vascular bed, the blood expelled from the rightventricle takes the path of least resistance, and retrogradeshunting occurs at the level of the aortic isthmus (Figure 3).

This finding has been reported to become evidentapproximately 12 days prior to decompensation or fetaldeath.22 In the presence of retrograde aortic isthmus flow,poorly oxygenated right ventricular blood, intended for theplacenta and lower body, mixes with oxygenated leftventricular blood and perfuses the brain, thereby reducingthe mean oxygen tension in the cerebral vascular bed. Theexact meaning of this finding is unknown, but some studiessuggest that this may negatively affect long-termdevelopmental outcomes of the affected offspring.23

If IUGR is allowed to progress even further, usually inthe setting of extreme prematurity, where the clinicianattempts to maximize gestational age before delivery,extensive diastolic cardiac dysfunction will result inimpaired preload handling. This can be documented as aprogressive increase in pulsatility index in the ductusvenosus,22 manifested initially as deepening and ultimatelyreversal of the a-wave.24 A pulsatile flow pattern can occurin the umbilical vein. If the fetus remains in utero, the riskof demise is very high. A prospective multicenter study,which included more than 600 live-born growth-restrictedinfants, showed that the ductus venosus Doppler was astrong predictor of neonatal mortality and morbidity ininfants born after 27weeks gestation whose birth weightwas over 600 g.25

In survivors, the cardiac changes observed antenatally maynot resolve at birth. Cripsi et al. reported that these childrenmaintain more globular hearts with impaired ventricularrelaxation, whereas others documented decreased strokevolumes, early onset hypertension and increased intima-mediathickness,21,26,27 resulting in a significantly increased risk forpremature cardiovascular disease.28

Functional echocardiography has given us a betterunderstanding of the sequence of events starting atplacental failure and ending with postnatal cardiovasculardisease. The challenge for clinicians and researchers nowlies in identifying how to modulate the growth-restrictedneonate’s primed phenotype to prevent adverse eventslater in life. This area must become a priority inperinatal research.

Figure 2 Representative Doppler waveforms in a monochorionic twin pair affected by stage IV twin–twin transfusion syndrome. Legend: leftpane: donor; right pane: recipient. Top line: myocardial performance index, middle line umbilical vein and ductus venosus; bottom line:tricuspid valve flow. ICT, isovolumetric contraction time; ET, ejection time and IRT, isovolumetric relaxation time. Note prolongation of ICTand IRT, biphasic umbilical vein pulsations, reversal of a-wave in ductus venosus, tricuspid regurgitation and decreased E/A ratio in therecipient fetus



VASCULAR TUMORS AND TWIN REVERSED ARTERIALPERFUSION (TRAP) SEQUENCEVascular fetal or placental tumors such as solid sacrococcygealteratomas (SCT), cavernous hemangiomas or chorioangiomasare rare. These masses can function as large arteriovenousanastomoses leading to a hyperdynamic fetal circulation.A slightly different but similar situation is encountered inTRAP sequence, wherein a healthy ‘pump’ fetus perfuses itsmonochorionic acardiac parasitic co-twin through placentalvascular anastomoses.

The hemodynamic effects of volume load on the fetal heartlargely depend on the size and vascularization of the tumormass or acardiac twin. The typical echocardiographic imageseen is a dilated heart with an increased cardiothoracic ratio.29

The cardiac output is increased and, in SCT, the inferior venacava, which drains the blood from the tumor to the heart, isoften widely dilated, suggesting an increased preload (Figure 4).Intrinsic myocardial function, as measured by the MPI,is typically preserved.29 In more advanced disease states,

however, cardiac failure develops, leading to polyhydramnios,hydrops and placentamegaly. At that stage, reversal of the a-wave in the ductus venosus and atrioventricular valveregurgitation may be observed, and the risk of intrauterinefetal demise is high.30

Close surveillance during pregnancy and timely diagnosis offast tumor growth with progression to high output failure arewarranted as these predict a worse fetal outcome.29,31 In thepresence of fetal decompensation (i.e. hydrops), deliveryshould be considered. In the previable period, fetal therapydirected at interrupting the blood supply toward the parasiticmass may be an option. In TRAP, this can be performed byocclusion of the acardiac twin’s umbilical cord (either byradiofrequency ablation or bipolar cautery), which results in80% survival of the pump twin.32,33 In SCT, open fetal surgeryor minimal invasive strategies aimed at interrupting the flowto the tumor may be attempted.34,35 Following successful fetaltherapy, cardiac output typically normalizes, and the highoutput state resolves.36

Figure 4 Sagittal magnetic resonance image (left) and ultrasound (right) demonstrating a widely dilated inferior vena cava (arrow) in a fetuswith a massive sacrococcygeal teratoma at 26weeks gestation

Figure 3 Graphical representation of the blood flow in the aortic isthmus in a normally grown fetus (A) and in severe growth restriction (B). (C)Clinical example of reversed aortic isthmus flow in a fetus with severe intrauterine growth restriction. Legend: red, oxygenated blood; blue,deoxygenated blood and purple, mixed oxygenated and deoxygenated blood



For now, assessment of cardiac output is used in adjunct toother (non-cardiac) parameters to select patients for fetaltherapy.31 Decisions on prenatal intervention should notbe taken on the basis of cardiac output alone, as in somefetuses’ high output states can be well tolerated for relativelylong periods.

INTRATHORACIC SPACE OCCUPYING LESIONSLarge lung lesions such as bronchopulmonary sequestrationsand congenital cystic adenomatoid malformations cancompress the heart and thus extrinsically limit right ventricularfilling. On echocardiography, this is evident as an increasedright ventricular MPI,37 an increased E/A ratio38 or a short,monophasic inflow pattern, and decreased cardiac output.37

Moreover, cardiac tamponade increases ventricular fillingpressure and the hydrostatic central venous pressure,39 which,if severe enough, will lead to hydrops. Similar hemodynamicchanges are also seen in other intrathoracic space occupyinglesions, such as congenital high airway obstruction, pleural orpericardial effusions, and pericardial teratomas.40–45

Although detection of hydrops in the previable period is anindication for fetal therapy,46 detailed monitoring of fetalhemodynamics has no role in the clinical management offetuses with congenital cystic adenomatoid malformations,and changes in cardiac output or ventricular filling alone arenot indications for intervention.47 Assessment of tumor sizemay be more indicative of the need for fetal therapy.48 The roleof functional echocardiography may be more important inevaluating pericardial effusions. Indeed, small effusions withrapid onset (such as those seen after an intracardiac fetalprocedure49) may sometimes be hemodynamically morechallenging for the fetus than large, gradually appearingeffusions, and echocardiography can help in guiding the needfor therapy.

In the left-sided congenital diaphragmatic hernia, theabdominal organs herniating into the chest cause mediastinalshift and result in altered ductus venosus streaming over theforamen ovale50 and a decreased left ventricular preload.Moreover, the hypoplastic lungs of diaphragmatic herniafetuses have a more muscularized pulmonary vasculature,which is more resistant to blood flow. As a consequence,venous return from the lungs to the left atrium is reduced,again decreasing the left ventricular preload. This leads to anunderfilled and thus smaller left ventricle51 and redistributionof the cardiac output toward the right ventricle.52 The oppositeobservations are true in the right-sided diaphragmatic hernia,where the right ventricle is smaller than in controls, and theright-sided cardiac output is reduced.53 Myocardial functionis nevertheless preserved.51 The degree of prenatal ventricularhypoplasia is not related to postnatal survival in infants withcongenital diaphragmatic hernia, but pulmonary blood flowmay be a predictor of pulmonary hypertension.54,55 Fetaltherapy for diaphragmatic hernia, which is aimed at promotinglung growth by temporarily occluding the fetal trachea, doesnot adversely affect cardiac function.51

Postnatally, with recovery of the preload and closure ofthe shunts between the left and right circulations, the

ventricular volumes recover, and long-term cardiac outcomesare normal.56

TWIN–TWIN TRANSFUSION SYNDROME (TTTS)Twin–twin transfusion syndrome complicates 10–15% of allmonochorionic twin pregnancies. Although itspathophysiology is poorly understood, vascular anastomosesin the placenta lead to a polyuric polyhydramnios in therecipient twin and oliguric oligohydramnios in the donor co-twin.57 In addition, the recipient fetus is hypertensive58 and,related to the high afterload, typically displays phenotypicsigns of hypertrophic cardiomyopathy with biventricularhypertrophy, atrioventricular valve regurgitation, diastolicdysfunction and later also systolic dysfunction.59–63 Thesefindings can be demonstrated both by ultrasound (ventricularwall thickening, mitral and tricuspid regurgitation,monophasic ventricular inflows, increased MPI, decreasedventricular strain63 and a-wave reversal in the ductus venosus;Figure 2) and biochemical markers of cardiac function in theamniotic fluid (natriuretic peptides and troponin).64 Thetypical TTTS phenotype predominantly affects the rightventricle and often precedes the picture of the full-blownclinical syndrome.65 Fetal cardiac function is worse in the moreadvanced Quintero stages66 of the disease, and, at least in stageI TTTS, worse cardiac function is predictive of diseaseprogression.67 In more severe TTTS, high afterload can resultin an acute right or less commonly, left ventricular failure witha picture of (reversible) functional pulmonary or aortic artresiawith no antegrade flow over the cardiac outlets and retrogradeflow in the ductus arteriosus or aortic arch.68,69

The echocardiographic findings in TTTS suggest that thedisease process is not only mediated by interfetal volume shifts(which would result in a picture of volume overload ratherthan a hypertensive cardiopathy) but that intertwin exchangeof vasoactive endocrine mediators such as endothelin-170 andthe renin-angiotensin system71 probably also plays animportant role. We find it interesting that, similar, but oftenmilder, changes in cardiac function to those seen in TTTS canbe observed in the larger fetus of monochorionic twinpregnancies affected by severe intertwin growthdiscordance,35,72,73 suggesting an overlap in pathophysiologybetween these conditions.

Fetal therapy, that is, fetoscopic laser ablation of the culpritplacental vascular anastomoses, has shown TTTS to be anexcellent demonstration of the regenerative capacity andplasticity of the fetal heart. Fetoscopic laser ablation that isnow the standard of care for severe TTTS74,75 does not onlyreverse the amniotic fluid discordance but after days to weeksalso leads to a full recovery of fetal cardiac function.69,76–78

Despite this, however, recipient twins remain at a higher riskfor congenital heart disease, including mainly pulmonarystenosis and septal defects78 and therefore, require closeantenatal and postnatal echocardiographic follow-up.

FETAL ANEMIAThe moderately anemic fetus typically is in a hyperdynamichigh output state as it tries to recirculate the availablehemoglobin more rapidly to maintain adequate tissue



perfusion. This, in combination with less viscous blood, leadsto higher blood flow velocities in the middle cerebral artery.Non-invasive Doppler measurement of these velocities canbe used to accurately assess the degree of fetal anemia.79

In the heart, a hypercontractile state can be observed,with increased shortening fractions and strain,80 resulting in ahigher cardiac output.81 Cardiomegaly seen in this ,settingis a sign of fetal compensation (increased ventricularvolumes to achieve a higher output) rather than a sign ofdecompensation.82 Severe anemia may lead to cardiacischemia, poor cardiac contractility and ultimately, fetaldemise.

Importantly, and unlike the middle cerebral artery Doppler,cardiac findings do not necessarily correlate with the severityof fetal anemia and are therefore not helpful in the clinicalmanagement of this condition.83 Intrauterine transfusion,which is the state-of-the-art therapy for severe fetal anemia,partially corrects the cardiac findings in utero.80 In childhood,however, reduced left ventricular mass and left atrial area havestill been reported,84 the clinical implications of which areunclear as of yet.

PELVIC MASSESDilated intra-abdominal structures such as a megacystis dueto lower urinary tract obstruction 85 or large ovarian cysts86

can compress the fetal abdominal and pelvic vessels andcause increased downstream resistance on the rightventricle. This can result in ventricular hypertrophy, alteredventricular filling (higher reliance on the atrial contractionas evidenced by a decreased E/A index and a higherpulsatility index in the ductus venosus), tricuspidregurgitation, cardiomegaly and pericardial effusions.85

These changes are however reversible after therapy87 andlikely of little clinical significance.

CONGENITAL INFECTIONSThe most common infections causing fetal myocarditis arecytomegalovirus88 and human parvovirus B19.89 Althoughcytomegalovirus is most commonly present with otherevidence of infection, such as ventriculomegaly andintracranial and abdominal calcifications or IUGR, theinfection can also be present in dilated cardiomyopathy.90

The fetus with parvovirus B19 on the other hand, whensymptomatic, almost always has cardiac signs, either dueto severe fetal anemia (see previous discussion) oroccasionally to acute myocarditis, which is present onultrasound as cardiomegaly with variably abnormal diastolicand systolic function parameters, marked ascites or full-blown hydrops.91 Arrhythmias, due to inflammation of theelectric conduction system, are very rare.89

MATERNAL CONDITIONS AFFECTING THE FETAL HEARTMaternal Graves disease can cause fetal hyperthyroidismthrough transplacental passage of thyroid stimulatingantibodies. Similar to experiments in lambs,92 fetalhyperthyroidism will cause sinus tachycardia in the range of180–200 beats per minute with an ensuing increase in fetalcardiac output. In case of mild to moderate fetal

hyperthyroidism, additional findings can include rightventricular hypertrophy with preserved ventricular functionand pericardial effusions.93 These signs disappear after birth,when thyroid function normalizes.93 In more extreme cases,if the tachycardia is uncontrolled, fetal cardiac failure, hydropsand intrauterine death can occur.

The cardiomyopathy observed in fetuses of diabeticmothers is the consequence of fetal hyperinsulinism94 andoccurs both in well and poorly controlled diabetics.95,96

Severity of the disease, however, is dependent on glycemiccontrol, and severe forms affecting cardiac function arealmost exclusively seen in poorly controlled diabetes.Diabetic cardiopathy occurs both in pre-gestational andgestational diabetes. The myocardial hypertrophypredominantly affects the interventricular septum but mayalso involve the free walls symetrically.97 This myocardialhypertrophy resolves after birth, when insulin levelsnormalize, leaving no long-term consequences98,99 but mayhave severe implications antenatally when obstructionoccurs at the level of the outflow tracts.

Although usually only noticed by echocardiography inthe third trimester of pregnancy, the myocardium ofdiabetic fetuses may already be abnormal from earlypregnancy onwards, with decreased ventricular compliance(diastolic dysfunction), as evidenced by abnormalventricular inflow patterns,100 atrial shortening fractionand isovolumetric relaxation time.101,102 Interestingly, someof these changes are also noted in diabetic fetuses withoutmyocardial hypertrophy. Systolic function was typicallythought to be preserved, yet use of more sensitiveultrasound techniques reveals that subtle changes incardiac strain may be present in the hearts of fetuses ofdiabetic mothers.103

Similar to the observations in congenital infections,maternal systemic lupus erythematosus can cause a fetalmyocarditis with ensuing endocardial fibroelastosis, dilatedcardiomyopathy and complete heart block due totransplacental passage of anti-Ro antibodies.104 Although theincidence of neonatal heart block is low (less than 2% of infantsof mothers with anti-Ro antibodies), the mortality andmorbidity are significant and related to the life-longdependency on postnatal pacing.104

CONCLUSIONSWe have described the alterations in fetal cardiac function thatare seen in the more common non-cardiac fetal pathologies. Inmost cases, when the extra cardiac fetal disease is mild, thesechanges will remain subclinical, go unnoticed on routineobstetric ultrasound and reverse after treatment. In moresevere cases, however, alterations in fetal cardiac functionmay become clinically apparent and lead to fetaldecompensation (hydrops and death).

In selected conditions, functional echocardiography mayhelp in guiding clinical decision-making regarding a need forearly delivery or offering antenatal therapeutic intervention.Obstetricians, sonographers and fetal medicine specialistsshould therefore be familiar with the (basic) fetal cardiacfunction assessment to evaluate the hemodynamic state in a



fetus with extra cardiac disease. This would include at leastrough estimates of systolic (eyeballing ventricular contractility)and diastolic functions (ventricular inflow pattern, valvularregurgitation and ductus venosus Doppler). If function appearsimpaired, a more detailed assessment in a fetal cardiology unitis indicated.

The growth-restricted fetus may represent a specialindication for performing routine functional cardiacassessment. More research is needed to define which, if any,novel functional indices should become part of our clinicalarmamentarium when evaluating the fetus with IUGRantenatally and in following, the growth-restricted neonate.

WHAT’S ALREADY KNOWN ABOUT THIS TOPIC?

• Fetal cardiac function can be altered in fetuses with extra cardiacdisease.

WHAT DOES THIS STUDY ADD?

• This article summarizes the changes in fetal hemodynamics seen infetuses with non-cardiac disease and demonstrates how fetalcardiac function assessment can improve our understanding of thepathophysiology of these conditions.

• The manuscript reviews how fetal hemodynamic assessment canhelp in guiding the clinical management of the sick fetus.

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Functional echocardiography in the fetus with non cardiac disease

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Transcript of Functional echocardiography in the fetus with non cardiac disease