Diagnosis and management of heart failure in the fetus

Abstract

Heart failure can be defined as the inability of the heart to sufficiently support the circulation. In the fetus, heart failure can be caused by a myriad of factors that include fetal shunting abnormalities, genetic cardiomyopathies, extracardiac malformations, arrhythmias and structural congenital heart disease. With advances in ultrasound has come the ability to characterize many complex conditions, previously poorly understood. Fetal echocardiography provides the tools necessary to evaluate and understand the various physiologies that contribute to heart failure in the fetus. In this review, we will explore the different mechanisms of heart failure in this unique patient population and highlight the role of fetal echocardiography in the current management of these conditions

Introduction

In this review the authors will explore the different mechanisms of heart failure in the fetus and highlight the role of fetal echocardiography in the current management of these conditions. Doppler echocardiographic tools to assess the fetus with congestive heart failure Doppler echocardiography is an important tool in the assessment of the fetus with congestive heart failure. In fetuses with altered hemodynamics secondary to congenital heart disease, arrhythmia, fetal anemia, intrauterine growth retardation, twin to twin transfusion syndrome, or significant extra cardiacanomalies known to impact the fetal cardiovascular system, Doppler derived echocardiographic parameters may help to quantify the degree of cardiac compromise that otherwise may not be evident with 2D and color Doppler techniques alone. The fetal cardiovascular score, shown in Table 1, comprises a number of Doppler parameters, to assess fetal well being and has been shown to correlate well with adverse outcome in fetuses with hydrops fetalis.¹

Table I.

The Fetal Cardiovascular Profile Score for the Assessment of Fetal Ventricular Dysfunction

	Normal 2 points	-1 point	-2 points
Hydrops fetalis	None	Ascites, pleural effusion, or pericardial effusion	Skin edema
Abnormal venous Doppler	Normal venous Doppler	Reversal with atrial contraction in the ductus venosus	Umbilical venous pulsations
Cardiomegaly (CT ratio)	CT ratio ≤ 0.35	CT ratio >0.35 and <0.50	CT ratio >0.50
Abnormal myocardial function	Ventricular shortening fraction >0.28 and no valve regurgitation	Ventricular shortening fraction <0.28 or tricuspid or semilunar valve regurgitation.	Tricuspid regurgitation and ventricular dysfunction or any mitral regurgitation
Abnormal arterial Doppler	Normal umbilical artery diastolic flow	Absent end-diastolic flow in the umbilical artery	Reverse end-diastolic flow in the umbilical artery

Umbilical artery and vein

Doppler flow patterns within the umbilical cord are frequently abnormal in fetuses with congestive heart failure. Doppler sampling within the umbilical artery reflects downstream resistance within the placenta. Accordingly, the resistance within the umbilical artery is generally quite low in order to promote blood flow to the placenta so that nutrients and gases may be effectively exchanged. As shown in Figure 1, the Doppler flow pattern within the umbilical artery is characterized by continuous forward flow both in systole and in diastole. In cases of underlying congestive heart failure or frank hydrops fetalis, the placenta may also become congested, leading to elevated resistance. As a consequence, the diastolic velocity within the umbilical cord decreases and may even be absent. Diastolic flow reversal within the umbilical artery, as shown in Figure 1 is a marker for poor outcome and a risk factor for in utero fetal demise.^2–4 Doppler assessment of the umbilical vein reflects systemic venous pressure. As systemic venous pressure rises in heart failure, changes within the Doppler flow patterns are first seen in the inferior vena cava, then in the ductus venosus, and finally in the umbilical vein. Only the most severe derangements in systemic venous pressure are reflected as changes within the umbilical venous Doppler flow pattern. The umbilical venous Doppler flow pattern is usually described as mildly phasic, low velocity flow (Figure 2). Respiratory variation may be seen if the Doppler sample is not acquired during fetal apnea. With increases in central venous pressure, notching is first seen at end-diastole, corresponding to atrial contraction. In cases of severe congestive heart failure or hydrops fetalis, venous pulsations may be seen.

Figure 1.

Umbilical artery Doppler flow patterns. A) Normal Doppler flow pattern of the umbilical artery; B) decreased diastolic flow; C) diastolic reversal of flow

Figure 2.

Umbilical venous Doppler flow patterns. A) Normal flow pattern of the umbilical vein with low velocity, phasic flow; B) demonstrates venous pulsations in the umbilical vein.

Ductus venosus

The ductus venosus is a key structure in fetal life, which enables the highly oxygenated blood returning from umbilical vein to enter the inferior vena cava, thereby bypassing the liver. Absence of the ductus venosus may be associated with congestive heart failure and hydrops fetalis — especially in cases where the liver is bypassed entirely and all umbilical venous return is directed into the right atrium, leading to high output heart failure.^{5, 6} Given its proximity to the heart, abnormalities in the ductus venosus Doppler flow pattern may be seen prior to any changes within the umbilical vein. Figure 3 illustrates the normal Doppler flow pattern in the ductus venosus. In fetuses with underlying congestive heart failure, the a wave velocity, corresponding to atrial contraction, decreases initially and then may become reversed.

Figure 3.

Ductus venosus Doppler flow patterns. A) Normal Doppler flow pattern of the ductus venosus; B) decreased flow with atrial contraction; C) reversal of flow with atrial contraction.

Middle cerebral artery

Doppler assessment of the middle cerebral artery provides vital information about overall fetal health as well as about cerebrovascular resistance. Figure 4 demonstrates the normal Doppler flow pattern of the middle cerebral artery. Generally, most of the flow occurs during systole with only a small amount of flow in diastole. An elevated peak systolic velocity within the middle cerebral artery may suggest underlying fetal anemia as the etiology of heart failure and/or hydrops fetalis.⁷

Figure 4.

Middle cerebral artery Doppler flow patterns. A) Normal Doppler flow pattern of the middle cerebral artery; B) elevated peak systolic velocity in a fetus with fetal hydrops secondary to anemia.

In fetuses with normal hemodynamics, the cerebrovascular resistance should be greater than the placental resistance; a cerebroplacental resistance ratio >1.08.⁸ However, in fetuses with inadequate cardiac output or chronic hypoxia secondary to intrauterine growth retardation, there may be “cephalization” of flow with lower resistance in the brain compared to the placenta. Indeed, fetuses with intrauterine growth restriction and a cerebroplacental resistance ratio < 1.08 have been shown to be at increased risk for adverse perinatal outcome.⁹

Tricuspid and mitral valve

The normal Doppler inflow pattern across the mitral and tricuspid valve is biphasic, with a lower e wave velocity, representing passive filling, and a dominant a wave velocity, representing active atrial contraction (Figure 5). Compared to mature myocardium, fetal myocardium is comprised of greater non-contractile elements.¹⁰ As a consequence of this inherent diastolic dysfunction, a greater percentage of ventricular filling occurs during active atrial contraction rather than during passive filling. This, in part, explains why fetuses with underlying arrhythmias are at increased risk of developing hydrops fetalis. In complete heart block, the atria are contracting against a closed atrioventricular valve. Without the contribution of active atrial contraction to ventricular filling, preload may become compromised, resulting in an overall diminished cardiac output. Similarly, in fetuses with supraventricular tachycardia or atrial flutter, there is diminished time for ventricular filling, leading to an overall reduced cardiac output.

Figure 5.

Atrioventricular valve Doppler inflow patterns. A) Normal Doppler flow pattern of the atrioventricular valve. There is a biphasic inflow pattern with a dominant a wave and a smaller e wave. B) Monophasic inflow pattern with fusion of the e and a waves.

Fetuses with congestive heart failure may have diminished ventricular compliance. As a consequence, there may be a monophasic Doppler inflow pattern, characterized by fusion of the E and a waves (Figure 5). In addition, mitral and tricuspid regurgitation are commonly seen in the fetus with congestive heart failure.^11–14 According to the cardiovascular profile score, a monophasic inflow pattern ^{11, 14} or the presence of mitral regurgitation are markers of more severe disease.¹¹

Ductus arteriosus

The ductus arteriosus is a key fetal structure. Through streaming patterns, it allows oxygen-poor blood pumped by the right ventricle to bypass the fetal lungs and return to the placenta via the descending aorta. Significant constriction of the ductus arteriosus imposes greater afterload on the right ventricle, which can lead to right ventricular hypertrophy, tricuspid regurgitation, and ultimately, congestive heart failure and hydrops fetalis secondary to right ventricular failure.^15–17 Figure 6 shows the usual Doppler flow pattern of the ductus arteriosus in a normal fetus and in a fetus with severe ductal constriction.

Figure 6.

Ductus arteriosus Doppler flow patterns. A) Normal Doppler flow pattern of the ductus arteriosus; B) Doppler flow pattern in a fetus with ductal constriction.

Assessment of fetal cardiac function via doppler derived techniques

A number of different Doppler derived indices and techniques may be useful in the fetus to assess overall cardiovascular well being.

Ventricular ejection force

The ventricular ejection force describes the acceleration of blood across the pulmonic or aortic valve over a specific time interval.¹⁸ This parameter is a reflection of systolic ventricular performance, which is derived from Newton’s laws. A higher value corresponds to greater force exerted in ejecting the ventricular volume of blood during systole. Ventricular ejection force is defined as (1.055 x the cross-sectional area of the valve x the velocity time integral during the acceleration phase of the cardiac cycle) x (the peak systolic velocity of the Doppler envelope/time to peak velocity), where 1.055 represents the density of blood.¹⁸ The ventricular ejection force should increase over the course of gestation. ^{19, 20} However, in fetuses with intrauterine growth retardation, the ventricular ejection force is diminished compared to normal controls.²¹ Fetuses with severely decreased ejection forces are more likely to have derangements in acid base status and are more at risk for postnatal complication or in utero fetal demise.²¹

Myocardial performance index

The myocardial performance index, otherwise known as the Tei index, is a Doppler derived technique that assesses both systolic and diastolic function.²² As shown in Figure 7, it is defined as the isovolumic contraction time + the isovolumic relaxation time/ejection time.²² An alternative definition is the time from atrioventricular cessation of flow to the time of atrioventricular onset of flow minus ejection time divided by the ejection time. A higher myocardial performance index value corresponds to a greater degree of global ventricular dysfunction, but does not distinguish between systolic or diastolic components. Normal values for the fetal right ventricular and left ventricular myocardial performance index have been published. The normal right ventricular myocardial performance index ranges from 0.35±0.05 to 0.43±0.05.^{23, 24} The normal left ventricular myocardial performance index ranges from 0.35±0.03 to 0.40±0.05.^23–25 Abnormalities of the myocardial performance index have been demonstrated in different pathological conditions such as maternal diabetes mellitus,^{26, 27} cardiomyopathy,²⁷ intrauterine growth retardation,^{26, 27} and in recipient twins of TTTS.^{23, 27–29} Higher myocardial performance indices correlate with worse outcomes for fetuses with hydrops fetalis.¹ Consequently, serial evaluation of this parameter over the course of gestation might guide practitioners in timing of delivery or prenatal interventional strategies prior to the onset of frank hydrops fetalis or intrauterine fetal demise. Investigators have demonstrated an improvement in the myocardial myoperformance index after laser procedure for the TTTS.^{28, 30}

Figure 7.

Myocardial performance index (Tei index). The above panel illustrates the measurement of the myocardial performance index. The isovolumic contraction time (ICT) and isovolumic relaxation time (IRT) may be individually summed and then divided by the ejection time (ET). Alternatively, the ejection time (b) can be subtracted from time from cessation of flow to the onset of flow across the atrioventricular valve (a) and then divided by the ejection time (b).

Tissue Doppler imaging

Pulsed-wave Tissue Doppler imaging (TDI), assesses peak regional myocardial velocities⁽³¹⁾. Compared to conventional Doppler techniques, TDI is less load dependent, and therefore may allow for earlier detection of myocardial dysfunction.³² The cardiac cycle is comprised of three waveforms: Sa, systolic myocardial velocity, Ea, early diastolic myocardial velocity during passive ventricular filling, and Aa, myocardial velocity during active atrial contraction. Multiple studies have demonstrated the feasibility of determine TDI in the fetus ^33–35 and reference ranges for these myocardial velocities over the course of gestation have been established on a 4-chamber view of the fetal heart at the lateral mitral annulus, the lateral tricuspid annulus, and the interventricular septum.³³ Recently, researchers documented the utility of TDI compared to conventional echocardiography in the assessment of cardiac dysfunction in early onset intrauterine growth retardation.³⁶ Compared to control fetuses, fetuses with intrauterine growth retardation assessed by TDI techniques demonstrated lower systolic and diastolic myocardial velocities at the mitral and tricuspid annulus, a higher mitral Ea/Aa ratio, and higher mitral, tricuspid, and septal myocardial performance index values.³⁶

Combined cardiac output

Combined cardiac output is determined by summing the right and left cardiac outputs, individually calculated according to the formula: semilunar valve cross sectional area x fetal heart rate x velocity time integral across the valve in systole. Stroke volumes are often diminished in the setting of heart failure. As a consequence, the peak systolic velocity across either semilunar valve is frequently low for gestational age. Determination of the combined cardiac output has been used clinically in a variety of volume loading conditions, such as fetuses with a sacrococcygeal teratoma and the pump twin in the twin-reversed arterial perfusion. We have previously found that fetuses with combined cardiac outputs > 800 cc/kg/min are at greatest risk for the development of hydrops fetalis and in utero fetal demise.³⁷

Conditions potentially leading to development of heart failure in the fetus

Agenesis of the ductus venosus

The ductus venosus is a fetal structure that shunts blood flow from the afferent venous system of the liver to the efferent venous system from the liver. This connection also provides a resistive circuit to regulate the amount of flow through the vessel.³⁸ Highly oxygenated blood from the umbilical vein drains into the portal sinus, where blood drains either to the intrahepatic portal veins or the ductus venosus. The ductus venosus bypasses the liver to drain into the subdiaphragmatic vestibulum, which connects to the inferior vena cava. The right and left hepatic veins also drain to the subdiaphragmatic vestibulum. The unique anatomic architecture of this network of vessels allows for preferential delivery of highly oxygenated blood from the umbilical vein, via the ductus venosus, towards the patent foramen ovale to the left side of the heart. This streaming allows for transport of highly oxygenated blood to the coronary arteries and cerebral vasculature.

Resistance within the ductus venosus is variable, changing with gestation and with different physiologic conditions. In a normal fetus, approximately 30% of flow from the umbilical venous return goes through the ductus venosus in mid-gestation. By the end of gestation, the amount of umbilical venous flow going through the ductus venosus reduces to approximately 20%.³⁹ If a fetus is in distress due to hypoxemia or placental insufficiency, the resistance within the ductus venosus decreases to allow for increased preferential streaming to the left side in order to perfuse the myocardium and brain with highly oxygenated blood.⁴⁰

Agenesis of the ductus venosus occurs in two varieties, depending on the site of attachment of the umbilical vein to the fetal vasculature.⁴¹ If the umbilical vein connects directly to the portal vein, highly oxygenated blood is routed through the capillary bed of the liver to reach the subdiaphragmatic vestibulum and enter the IVC and heart. In this scenario, although preferential streaming of highly oxygenated blood to the left heart is impaired, the liver provides a resistive circuit between the umbilical vein and the heart. As a result, there is no significant volume overload that affects the fetus. Alternatively, the umbilical vein may connect directly to an extrahepatic structure, such as the femoral or iliac vein, the IVC, the coronary sinus or the atria. In this type of agenesis of the ductus venousus, there is no resistor to regulate flow from the umbilical vein to the heart. Without the resistor, significant congestive heart failure and hydrops can develop in the fetus.⁴²

Additional factors beyond volume overload and cardiac dysfunction may make such fetuses prone to hydrops. Agenesis of the ductus venosus is associated with genetic abnormalities, such as Turner’s syndrome and Noonan’s syndrome.⁴³ One theory is that lymphatic drainage abnormalities associated with genetic aberrations may contribute to the development of hydrops. Another theory is that liver development may be altered or that deposition of a hepatic factor to prevent hydrops could be impaired.

Fetuses with agenesis of the ductus venosus may demonstrate an enlarged IVC, cardiomegaly, ventricular dilation with atrioventricular valve regurgitation, and increased peak velocities across the valves.⁴⁴ When the combined cardiac output reaches more than 750 to 800 mL/kg/min, the patient is at risk for hydrops. Medical management for the fetus with agenesis of the ductus venosus resulting in congestive heart failure can include anticongestives such as digoxin. However the definitive treatment is delivery if the fetus has reached an adequate gestational age.

Constriction and premature closure of the ductus arteriosus

The ductus arteriosus shunts blood from the pulmonary artery to the descending aorta. Sixty percent of systemic venous return in the fetus is directed towards the right ventricle, while the remainder is shunted across the patent foramen ovale. The blood in the right ventricle is then pumped to the main pulmonary artery. While 10% of flow is directed to the lungs to perfuse the developing lung parenchyma in early gestation, the remaining 90% of flow travels across the ductus arteriosus to the descending aorta, supplying blood to the abdomen, pelvis and lower extremities of the fetus. Towards the end of gestation, the flow to the branch pulmonary arteries increases to approximately 20–25% of the entire cardiac output.⁴⁵

Constriction and premature closure of the ductus arteriosus can lead to potentially significant negative consequences. Obstruction of flow from the pulmonary artery to the descending aorta in the setting of high pulmonary vascular resistance leads to a large increase in afterload on the right ventricle. This results in right ventricular hypertrophy and diminished right ventricular compliance. The consequence to this can be increased right to left shunting at the level of the PFO, pulmonary and tricuspid regurgitation, and pulmonary hypertension. With significant diversion of blood flow away from the right heart across the PFO, right ventricular hypoplasia, as well as pulmonary stenosis or pulmonary atresia may also develop, depending on the timing of the constriction or closure of the ductus arteriosus. Once right ventricular systolic function becomes sufficiently impaired, fetal hydrops may ensue.

Three outcome models for premature ductal constriction or closure are described by Gewillig et al.⁴⁶ The first model demonstrates aneurysmal dilation of the branch pulmonary arteries, pulmonary insufficiency and stenosis with thickening of the pulmonary valve. This dilation of the pulmonary arteries leads to compression of the airway, resulting in respiratory insufficiency vasonce the fetus is delivered. The second model describes isolated pulmonary stenosis and insufficiency that can be associated with right ventricular hypertrophy and/or hypoplasia. The third model demonstrates pulmonary hypertension in the neonatal period with right ventricular hypertrophy and right ventricular dysfunction. There are a myriad of causes of premature constriction and closure of the ductus arteriosus. While many cases are idiopathic, non-steroidal anti-inflammatory agents, salicylates, sympathomimetics and certain herbal beverages and creams have all been implicated in triggering this phenomenon.⁴⁷ On fetal echocardiography there may be ventricular size discrepancy with a dilated, hypertrophied right ventricle, a narrowed ductus arteriosus by two dimensional imaging for gestational age, right atrial dilation, and tricuspid and pulmonary regurgitation. High systolic and diastolic velocities may be noted within the ductus arteriosus, directed towards the descending aorta. The pulsatility index is typically diminished at <1.8.⁴⁸

Treatment for constriction of the ductus venosus is elimination of the inciting agent, if applicable. If severe right ventricular dysfunction with impending hydrops is present, delivery with access to nitric oxide for pulmonary vasodilation should be considered. Postnatal echocardiography typically demonstrates a small or absent patent ductus arteriosus within the first 24 hours of life, marked cyanosis and small, thick right ventricular cavity. Patient outcomes vary in severity based on the degree and duration of constriction, as well as the developmental stage at the time of the event in fetal life.

Restriction and closure of the patent foramen ovale

The foramen ovale provides a connection between the right atrium and the left atrium of the heart in fetal life. It allows 40% of systemic venous return to shunt across the atrial septum to the left heart. Heart failure in the fetus is very rare in isolated forms of restriction or closure of the patent foramen ovale, but has been reported in the literature.⁴⁹ More commonly it is appreciated in certain forms of congenital heart disease with obligate shunting across the atrial septum and/or left atrial hypertension. Fetal distress is more likely to be appreciated in patients with obligate right-to-left shunting, such as tricuspid atresia or pulmonary atresia due to higher blood volume required transit across the atrial septum.

Twin-twin transfusion syndrome

Twin-twin transfusion syndrome (TTTS) is a form of placental vasculopathy that occurs in monozygous, monochorionic multiple pregnancies. This disorder is seen in 10–20% of monochorionic twin gestations and has a fatality rate of 80% or more for one or both twins if left untreated.⁵⁰ A diagnosis of TTTS should be suspected if there is a 10% or more size discrepancy between monochorionic twins, with oligohydramnios in the smaller fetus and polyhydramnios in the larger fetus. Changes within the fetuses may be appreciated as early as 14–16 weeks gestation with rapid progression of cardiovascular changes from 18–28 weeks gestation. There is no known genetic predisposition to this phenomenon.⁵¹ TTTS is mediated by an abnormal vascular network within the placenta that allows for exchange of volume and vasoactive mediators between the two fetuses. In a normal twin monochorionic pregnancy, arterial-to-venous connections within the placenta allow for exchange of volume between the fetuses. Meanwhile, arterial-to-arterial connections promote equilibration of net flow between the fetuses and stabilization of circulatory volume. If there are an inadequate number of arterial-to-arterial connections with an excess of flow through arterial-to-venous connections, volume depletion will occur in one twin, while volume overload will occur in the other twin.⁵²

The cascade of events leading to the development of TTTS begins with net transfer of volume between donor and recipient due to the abnormal vascular connections. The donor twin becomes hypovolemic and responds with an increase in systemic vascular resistance to maintain adequate perfusion pressure via multiple mediators, including endothelin-1 and angiotension II.⁵³ The renin-angiotensin system within the recipient placenta may also contribute to this process.⁵⁴ The recipient twin becomes volume overloaded but also receives the vasoactive mediators released by the donor and the placenta. The donor twin demonstrates features of small heart size with underfilled ventricular cavities, hyperdynamic systolic ventricular function, oliguria and oligohydramnios. Meanwhile the recipient develops cardiomyopathy due to volume overload with polyhydramnios.

Without intervention, 10% of recipient twins will develop “acquired” congenital heart disease with pulmonary stenosis and right ventricular outflow tract obstruction.⁵⁵ This reflects an element of plasticity of the fetal heart, with development of structural heart disease not present at the time of heart formation in the setting of changing flow dynamics, loading conditions and vasoactive mediator release. Impairment of cerebral perfusion in the recipient twin may result from the cardiomyopathy, while poor growth is seen in the donor due to hypovolemia and oliguria.⁵⁶ If left unchecked, severe ventricular function can lead to hydrops and fetal demise. Following the death of one twin, the vascular connections remain and can form a vascular sink that drains the blood volume of the surviving fetus. This may lead to further neurological insult and can also result in the demise of the remaining twin.

A comprehensive assessment of both fetuses by echocardiography is indicated in patients with suspected TTTS.⁵⁷ At first cardiac output in the recipient is increased in comparison to the donor. However, as the disease progresses and diastolic and systolic function deteriorates, cardiac output diminishes. Changes in function typically begin and worsen in the right heart and are later seen in the left heart. Echocardiographers should evaluate the recipient twin for signs of volume overload and congestive heart failure. Diastolic changes in the E:A ratio in the inflow patterns of the AV valves and an evaluation for pulmonary insufficiency, pulmonary artery hypoplasia, and RVOT obstruction should be performed. Umbilical artery flow with absence or reversal of diastolic flow can result from elevated placental resistance and is a risk factor for fetal demise.

There are several systems of analysis available to determine the severity of TTTS. Quintero and colleagues developed a system of five grades based on clinical and ultrasound features.⁵⁸ A more comprehensive scoring system with four grades of severity evaluating five domains of cardiovascular findings is used at Children’s Hospital of Philadelphia (Figure 8).⁵⁹ Four of the categories relate to findings in the recipient twin, which include ventricular elements, valve function, venous Doppler and analysis of the great vessels. The remaining category evaluates umbilical artery flow in the donor twin.

Figure 8.

CHOP TTTS Cardiovascular Score.

There are several treatment options for TTTS. Laser photocoagulation (LP) is a relatively new technique that significantly improves the morbidity and mortality of this disorder. LP selectively disrupts the placental vascular connections contributing to TTTS.⁶⁰ Efficacy of this technique has been demonstrated in unpublished data from Children’s Hospital of Philadelphia. In a series of 54 patients, on average the CHOP TTTS Cardiovascular Score decreased by half within one week of treatment. Another study demonstrated that myocardial performance index measurements showed improvement within 1 month with complete normalization.⁶¹ However, once there was clear pulmonary valvar stenosis with thickened, non-mobile leaflets or atresia, LP did not improve these findings. It appears that once the threshold is reached to generate this fixed structural abnormality, there is no longer plasticity with physiological changes. Another treatment option for TTTS is amnioreduction. Although not as efficacious as LP, this technique provides maternal relief from fluid accumulation and physiological improvement in the fetuses from alleviation of placental compression.⁶² If the disease is severe and fetal demise is anticipated, selective termination may be necessary to preserve the life of one fetus. This can be performed by an ultrasound bipolar cord cauterization technique, which is associated with improved outcomes for the surviving twin.

Once the fetuses are delivered, postnatal echocardiographic evaluation is warranted to assess for residual ventricular dysfunction, hypertrophy, and tricuspid regurgitation. Newborns can have an increased risk of persistent pulmonary hypertension, responsive to inhaled nitric oxide.⁶³ Patients with acquired pulmonary valve disease may require balloon valvuloplasty or surgery. Overall, survival has improved significantly with the current treatments. Laser photocoagulation now provides survival rates of 88–93% in at least one twin.⁶⁴ Improvement of neurological outcomes, vascular reactivity and endothelial function also provide hope for less long-term morbidity in this patient population.

Twin reverse arterial perfusion

Twin reverse arterial perfusion (TRAP) is a rare disorder in which there is a normal fetus whose heart provides blood flow not only to its own body, but also to the body of a twin with inadequate cardiac output. The normal twin is known as the “pump” twin, while the twin with a non-functional heart is known as the “acardiac” twin. The inciting cause of this disorder is unclear, although acardiac twins demonstrate a high rate of chromosomal abnormalities. This disorder occurs in 1 in 35000 pregnancies and in 1% of monochorionic pregnancies. In addition to twin gestations, it has also been reported to occur in triplet, quadruplet, and quintuplet gestations.^{65, 66}

In a TRAP gestation, the normal twin pumps blood to the placenta via the umbilical artery. Blood travels through arterial-to-arterial placental vascular anastomoses into the acardiac twin’s umbilical artery. This results in blood flow reversal in the acardiac twin’s umbilical artery, with flow headed toward its body from the placenta. Flow is also reversed in the acardiac twin’s umbilical vein and now exits the body of the acardiac twin and flows into the umbilical vein of the normal twin via veno-venous connections within the placenta. As a result, deoxygenated blood from the acardiac fetus is now delivered to the umbilical vein of the pump fetus. This results in a volume overload higher workload, and biventricular hypertrophy in the normal twin. Collectively, this leads to heart failure, hydrops and can result in fetal demise.

Poor outcome predictors for the pump twin with TRAP are when there is a >50% ratio between weights of acardiac and pump twin, as well as polyhydramnios and CHF in the pump twin. A lower umbilical artery PI in a rapidly growing acardiac twin with increased LV shortening fraction in the pump twin during the second trimester is also associated with adverse outcome.⁶⁷ One classification system to assess TRAP severity uses the ratio of the size of the acardiac twin to the pump twin of >50% and signs of cardiovascular compromise in the pump twin to indicate that an intervention is warranted.⁶⁵ The signs of compromise in the pump twin include moderate to severe polyhydramnios, cardiomegaly, pericardial effusion or abnormal Doppler signs, such as reversal of flow in the DV, UV pulsation, increased diastolic MCA flow and TR.

The mortality of this disorder for the pump twin is 50–75% without intervention. However with intervention, the perinatal survival of the pump twin improves dramatically to approximately 80–92%.^{68, 69} Radiofrequency ablation and laser coagulation can be performed on the acardiac twin umbilical cord.⁷⁰ There is an increased risk of preterm delivery after intervention. The pump twin may present with low cardiac output and require inotropic support and afterload reduction after delivery.

Fetal anemia

Red blood cell destruction, as well as poor or abnormal production, are causes of anemia in fetal life. Fetal anemia results in diminished oxygen carrying capacity to the developing tissues. In order to maintain adequate tissue oxygenation, cardiac output increases with an increase in myocardial stretching and filling pressures with decreased afterload, resulting in cardiomegaly. Coronary perfusion augments to supply the increasing demands of the myocardium with increased coronary perfusion pressure and decreased coronary resistance.⁷¹ Once the above adaptations can no longer compensate, myocardial ischemia occurs, resulting in diminished function and development of a dilated cardiomyopathy. This can lead to hydrops and fetal demise.

Parvovirus B19 is a common cause of anemia resulting from viral suppression of the bone marrow. The virus causes cytotoxic apoptosis and lysis of erythroid precursors, inhibiting erythropoiesis.⁷² Acute infection occurs in 1–2% of pregnant women, although epidemics occur in which the rate significantly increases.⁷³ Many cases are completely asymptomatic, with no ill effects on the mother or fetus. However, a subset of patients will develop significant adverse sequelae from the infection. Parvovirus B19 is transmitted vertically from mother to fetus during gestation in 30% of women, with a peak incidence of infection between 17–24 weeks, likely due to the increasing demands in red cell production during this window of gestation. The mortality rate for fetal infection is 5–10%. Cardiomyopathy secondary to parvovirus is predominantly due to fetal anemia, although myocarditis also exacerbates cardiac failure.⁷⁴

Another common cause of fetal anemia is genetic hemoglobinopathy. Hemoglobin Bart’s disease is a homozygous alpha-thalassemia that results in severe fetal anemia. Fetuses with this condition have no production of the alpha chains of hemoglobin, normally encoded by genes within the short arm of chromosome 16.75 Only gamma chains are produced, forming gamma chain tetramers, which transport oxygen poorly. This can lead to cardiomyopathy, hydrops and fetal demise. This condition may also result in “mirror syndrome” with maternal signs of heart failure, which puts the mother’s health at risk. Hemoglobin H disease is a disorder in which a patient has production of one out of four alpha chains.⁷⁶ This disease, along with several other forms of hemoglobinopathy, can lead to fetal heart failure.

Alloimmunization as a cause of hemolytic anemia of the fetus has become much less frequent with immunization with anti-D immunoglobulins to Rhesus-negative mothers. Anemia from alloimmunization is mediated by development of immunoglobulin G antibodies that form after contact with a previous antigen. The antibodies travel across the placenta into the fetal circulation, resulting in erythroblastosis. Immunization prevents sensitization of the maternal antibodies to Rhesus-positive antigens in future fetuses. Prior to immunization, Rh incompatibility resulting in alloimmunization was the main cause of fetal hydrops. There remain many other blood group systems that can also result in hemolytic anemia, including ABO, Kidd, Duffy, MNS, Kell, C and E.⁷⁷

Evaluation of the fetus with anemia by fetal echocardiography demonstrates cardiomegaly with hyperdynamic function in the initial period, leading to cardiomyopathy with diminished function and AV valve regurgitation as the disease progresses. An increase in peak systolic velocity of the middle cerebral artery (MCA) is an important marker of fetal anemia and can be followed serially, as it is inversely proportional to hemoglobin levels in the fetus.⁷⁸

Treatment options for fetal anemia include intrauterine transfusions administered through the umbilical vein.⁷⁹ This intervention is indicated when the MCA peak systolic velocity is 1.5 times above the mean and trending upward. Once the transfusion is given, MCA peak systolic velocities immediately decrease. N-terminal pro-B-type natriuretic peptide levels correspond to the degree of myocardial workload in the fetus and decrease with treatment.⁸⁰ If the fetus is viable, delivery is a consideration if there is hydrops.

Cerebral arteriovenous malformations

Another condition that can induce heart failure in the fetus secondary to volume overload is cerebral arteriovenous malformation (AVM). The most common type of AVM is the vein of Galen aneurysmal malformation (VGAM). This abnormality is an error in early vasculogenesis during the first trimester.⁸¹ Vein of Galen aneurysmal malformation is actually a misnomer, since an arteriovenous connection is actually formed by choroidal arteries and the precursor of the vein of Galen, called the embryonic prosencephalic vein of Markowski. Blood bypasses capillary beds, shunting to the venous system. VGAMs are associated with certain types of congenital heart disease.⁸² Sinus venosus type atrial septal defects are seen with VGAMs, potentially mediated by increased superior vena cava (SVC) flow during embryonic development. Coarctation of the aorta is associated with VGAM, thought to be secondary to cerebral steal, which draws blood away from the aortic isthmus and causes inadequate growth.

VGAM results in an increased volume load to the cerebral venous system and to the heart due to preferential flow to the low resistance circuit formed by the AVM. This causes marked dilation of the straight and sagittal sinuses and the cerebral venous system carrying this blood flow to the heart. As with other lesions causing volume overload, high-output congestive heart failure can result. In addition, mass effect from dilated vessels in the brain can cause brain hypoplasia and abnormal brain development. Cerebral hemorrhage and thrombosis have also been described.⁸³ Postnatally, seizures, hydrocephalus and developmental delays are consequences of this lesion.⁸⁴

On fetal echocardiography, there is typically dilation of the superior vena cava, right ventricle and pulmonary artery. As the right heart dilates, the tricuspid valve annulus can stretch, resulting in tricuspid valve regurgitation. Flow across the aortic isthmus may reverse in diastole due to the cerebral steal. Combined cardiac output is increased. If CCO is over 700–800 mL/kg/min, hydrops may result. No fetal intra-uterine therapies are currently available for those suffering from this disease. If there is a high risk of fetal demise, delivery may be warranted if the fetus has reached a viable gestational age. After birth, coil embolization via interventional radiology is 50–80% effective in management of heart failure.⁸⁵ Patients may require a ventriculo-peritoneal shunt if hydrocephalus persists despite embolization therapy.⁸⁶

Pulmonary arteriovenous malformation

Arteriovenous malformation within the pulmonary bed is another type of abnormality that results in heart failure secondary to volume overload. These malformations create a bypass of the capillary bed of the lung with a direct connection between the arterial and venous circulations. They are quite rare in the fetus. In adults, they are associated with hereditary hemorrhagic telangiectasia (HHT), however HHT is rarely associated with pulmonary AVMs in the fetus. ⁸⁷ Pulmonary AVMs in the fetus may be the result of remnants of an earlier primitive stage of normal embryonic development.⁸⁸

Support for this notion comes from the observation that hepatic venous flow influences the development of pulmonary AVMs. There is a known association of pulmonary AVMs in patients with single ventricle palliation when blood flow from the liver does not perfuse the lung tissue.⁸⁹

Fetal pulmonary AVMs create a low vascular resistance sink, promoting diversion of blood flow through the lung. This results in an increased volume load, which can ultimately lead to cardiomegaly, heart failure, and hydrops. By fetal echocardiography, there are signs of volume overload with significant left heart enlargement due to increase in pulmonary venous return.⁹⁰ The increase in pulmonary venous return also results in echolucent, dilated pulmonary veins. Left to right flow can be seen across the PFO as LA pressure increases. Ductal flow may also reverse. Flow travels from the aorta to the pulmonary arteries as blood follows the path of least resistance into the AVM, resulting in systemic steal.

Lung tissue itself may not be adequately perfused due to the steal of the AVM, leading to abnormalities in the pulmonary microvasculature.⁹¹ Consequences of the physiologic alterations in the neonate are profound postnatal hypoxemia due to intra- pulmonary shunt of blood away from the alveoli, acidosis, and potential pulmonary hypertension from abnormal lung development. Treatment options are limited for fetuses with this diagnosis. Delivery can be considered depending on gestational age of the fetus if there is a high risk for hydrops. Embolization of the AVM via an interventional catheterization can be performed using coils or a device.⁹²

Sacrococcygeal teratoma

Sacrococcygeal teratoma is a neoplasm originating from the sacral-coccygeal region of the body. This tumor typically consists of all three germ layers or can be defined by the presence of multiple tissues foreign to that location of the body lacking organ specificity. ⁹³ The tumor is thought to originate from totipotent somatic cells in the caudal region of the embryo. These cells do not undergo the typical controlled differentiation, but instead evolve into a random, growing mass made up of a variety of tissues that can invade the pelvic and abdominal cavities. The incidence of sacrococcygeal teratoma is 1 out of every 35000–40000 live births.⁹³ Mortality in the fetus is linked to effects of tumor mass and includes dystocia, preterm labor due to polyhydramnios, high output failure leading to fetal hydrops and placentomegaly, as well as spontaneous hemorrhage leading to fetal anemia.⁹⁴ Meanwhile, mortality in postnatal life is typically due to malignant degeneration.

Sacrococcygeal teratomas are large, fast-growing and highly vascularized structures that can contain significant arteriovenous malformations. This leads to an increased circulating blood volume to supply the tumor with increased preload returning to the heart, placing the fetus at risk for high output heart failure. The tumor also forms a low resistance vascular sink, potentially causing placental steal. On fetal echocardiography, the IVC is typically enlarged due to the increased blood volume returning to the heart. If placental steal occurs, a decrease in diastolic flow or even reversal of flow in the umbilical artery may be appreciated.

Treatment options for sacrococcygeal teratomas include amnioreduction for polyhydramnios, which provides maternal comfort and decreases the risk of premature labor. Cyst aspiration can be performed if the tumor contains large cystic structures.⁹⁵ Laparoscopic laser ablation directed at the vascular supply is also a treatment option. Open fetal surgery with fetal debulking can be performed if the life of the fetus is in danger late in the second trimester.⁹⁶ However this procedure carries significant risks due to acute hemodynamic changes. With removal of large portions of the tumor, a decrease in preload with an increase in afterload after the removal of the low resistance sink can develop.⁹⁷ The heart will appear hypertrophied with diastolic dysfunction once the ratio of mass to volume changes and can lead to fetal demise. As a result of this risk, delivery with postnatal treatment of the tumor is recommended after 26 weeks rather than fetal surgery. Long-term complications of sacrococcygeal teratomas include impaired bowel function, urinary incontinence, and a small risk of recurrence.

Congenital cystic adenomatoid malformation

Congenital cystic adenomatoid malformation (CCAM) is a benign hamartoma or dysplastic lung tumor overgrowing the terminal bronchioles in fetal life. Unlike bronchopulmonary sequestration, the arterial supply of the CCAM is derived from the pulmonary arterial tree. CCAMs are typically unilateral with involvement of one lobe of the lung. Histological examination of the CCAM demonstrates rapidly dividing cells with significantly lower rates of apoptosis than normal fetal lung tissue. Rat models suggest that fibroblast growth factor overexpression may lead to the development of CCAMs.⁹⁸ Nearly two-thirds of patients with CCAMs have a known localized genetic abnormality and some cases are reported with associated congenital heart defects.⁹⁹

CCAMs are variable in size and can become significant space-occupying lesions. ¹⁰⁰ Cysts within the structure develop in the setting of terminal bronchiole overgrowth. Macrocystic CCAMs have single or multiple cysts measuring 5 mm in diameter or larger in fetal life. If multiple cysts are present, they may communicate. Macrocystic CCAM development is thought to occur during the pseudoglandular stage between 7–17 weeks of gestation when there is rapid development of the conducting airways and peripheral lung tubules, which branch and bud to produce acinar tubules. Microcystic CCAMs appear more as a solid echogenic mass. Microcystic CCAMs are thought to develop during the canalicular phase between 17–29 weeks of gestation.

If a CCAM grows too large, it can compress and impair the growth of the adjacent lung tissue. The major cardiovascular consequences are due to compression of cardiac structures that impair forward flow. Compression of the heart can decrease preload, resulting in poor cardiac output.¹⁰¹ This can also lead to an increase in atrial pressure as well as systemic venous pressure, resulting in right heart failure and hydrops. Distortion of the heart from deviation of the atrial mass due to the space-occupying lesion can lead to kinking and obstruction of the IVC and further decrease preload, resulting in ascites. Pleural and pericardial effusions do not form due to increased intrathoracic pressure. Compression of the esophagus may affect swallowing and result in polyhydramnios.

On fetal echocardiography, findings are most consistent with impaired filling and cardiac tamponade. Patients with CCAM have a small cardiothoracic (CT) ratio compared with normal fetuses, and patients with CCAM and hydrops have a lower CT ratio compared to patients with CCAM without hydrops. The CCAM patients with hydrops have an increased E/A ratio in both AV valves, increased reversal of flow in the IVC with atrial contraction and UV pulsations. Ventricular function is normal to hyperdynamic, however MPI, which assesses overall systolic and diastolic function, is increased in patients with CCAM. These patients have a lower than normal ejection force and decreased combined cardiac output. The CCAM volume to head circumference ratio or CVR is calculated using this formula: (length x height x width x 0.52)/head circumference.¹⁰² High-risk patients demonstrate a CVR>1.6 or have lesions with a significant macrocystic component. The peak growth of these lesions is between 18–26 weeks, with a plateau or regression after 29 weeks. The indications for intervention include frank or impending hydrops, the presence of large macrocystic lesions, and/or cardiovascular abnormalities such as UV pulsation, low CT ratio or low CCO.

There are several treatment options for this anomaly. If the fetus is 32 weeks or less with no major genetic anomalies with single or multiple dominant cysts, fetal thoracoamniotic shunting is an option.¹⁰³ This can be performed percutaneously and reduces mass volume to help relieve tamponade and improve ventricular filling. If no dominant cyst is present but there is a high risk of fetal demise, open fetal surgery can be performed to remove the mass, which can resolve hydrops and promote growth of normal lung tissue.⁹⁶ The risks of open fetal surgery are secondary to coronary ischemia.⁹⁷ Higher diastolic pressures due to tamponade result in lower perfusion pressure required to fill the coronary arteries with blood. With surgical removal of the CCAM, higher perfusion pressure of the coronaries is needed, but the heart may still be unfilled. This creates a mismatch of supply and demand and can lead to myocardial ischemia. Signs of ischemia include marked bradycardia, ventricular dysfunction and TR. In order to avoid this complication, volume infusion is needed to improve preload during surgery.

Additional treatment options for fetuses with CCAM >32 weeks gestation and impending or frank hydrops is delivery with ex utero intrapartum treatment (EXIT) procedure. ¹⁰⁴ This procedure involves CCAM removal while the fetus is still connected to maternal placental circulation. If a patient is >34 weeks and >2000 g, ECMO may be an option if there is respiratory insufficiency or persistent pulmonary hypertension. High-dose steroid therapy recently became a treatment option to improve hydrops.¹⁰⁵ Maternal betamethasone administration improved survival in in a series of fetuses with CVR>1.6 in a recent study. The mechanism for this treatment is unclear, as size of lesion does not significantly decrease. If not life threatening, postnatal excision is performed at 5–8 weeks to decrease risk of infection, pneumothorax and malignancy.¹⁰⁶

Cardiac tumors

Primary cardiac tumors in the fetus can arise, grow and regress at a various times during gestation. Most are solitary, but they can also be multiple. The vast majority are benign tumors, however they can cause significant complications due to pericardial effusions, impaired ventricular filling, arrhythmias, myocardial dysfunction and hydrops. Cardiac tumors are a relatively rare finding in the fetus. One study showed that 0.14% out of 14000 fetal echocardiograms performed over an 8-year period demonstrated a cardiac mass.¹⁰⁷ Rhabdomyomas are the most common type of cardiac tumor seen prenatally and postnatally. One series of fetal and newborn cardiac tumors reported a distribution of 54% rhabdomyomas, 18% teratomas, 12% fibromas, 6% hemangiomas, 3% myxomas, 7% other.¹⁰⁸ While teratomas are the second-most common tumor in fetal life, fibromas become the second-most common cardiac tumor in infancy and childhood. Depending upon the location of the tumor and its degree of vascularity, cardiac tumors may cause heart failure by impairing flow, or result in volume load physiology.

Fetal cardiomyopathy

Cardiomyopathies in the fetus consist of a variety of disease processes in which cardiac muscle is not functioning properly. They make up 2–4% of all cardiovascular disease diagnosed in the fetus. Dilated cardiomyopathy (DCM) results when there is ventricular chamber enlargement with impaired cardiac function. It is typically caused by infectious agents, but can also occur in the setting of metabolic and/or genetic conditions. Meanwhile, hypertrophic cardiomyopathy (HCM) presents as abnormally thickened myocardium in the absence of structural heart disease.

Dilated cardiomyopathy

The most common cause of dilated cardiomyopathy in the fetus is viral myocarditis due to agents crossing the placenta. Common viruses linked to fetal myocarditis include parvovirus, coxsackie virus, toxoplasma, HIV and CMV. Maternal symptoms of the virus may be elicited, but not always. Fetal echocardiography can demonstrate cardiac dysfunction and pericardial effusions in the setting of inflammation of the myocardium. Dysfunction can resolve, but if significant myocardial damage occurs, functional abnormalities may persist.

A multitude of metabolic and genetic causes are linked to DCM in the fetus. Mutations on the X chromosome, such as the mutation of the tafazzin gene (TAZ) can cause the disease. Barth’s syndrome is a disorder caused by a TAZ gene mutation and can result in DCM with cyclic neutropenia and growth impairment.¹⁰⁹ Noncompaction of the LV that can result in DCM can be X-linked or idiopathic. Crypts within the LV apex and free wall characterize this disease. These non-compacted areas measure at least twice that of the compacted cardiac muscle wall. While some patients with noncompaction never develop significant cardiac dysfunction or symptoms, others eventually develop LV wall thinning and dilation with worsening cardiac function.

Infantile arterial calcinosis is another rare entity that can cause DCM. It is characterized by echo-bright calcification of the arterial walls of the great vessels, as well as other medium and large vessels.¹¹⁰ Histological examination of the vessels demonstrates calcification within the internal elastic lamina with extension to the intima and media. There is also giant cell reaction and proliferation of the smooth muscle. Diminished myocardial function in patients with infantile arterial calcinosis is thought to be secondary to coronary artery calcification with myocardial ischemia. Hypertension resulting from renal artery calcification can also occur. Possible improvement in infancy can be achieved with chelating agents and diphosphonate therapy.

Sialic acid Storage disease and mitochondrial disorders are also causes of DCM. Maternal autoimmune diseases, such as lupus and Sjogren’s, can result in DCM due to myocardial inflammation with associated conduction disease. Mothers are often asymptomatic, so SS-A and SS-B testing is recommended if DCM is seen in the fetus. Unique echo-bright regions of the myocardium within the atrium, AV groove or the crux of the heart have been seen in fetuses exposed to autoimmune processes.¹¹¹

In the fetus with dilated cardiomyopathy, on fetal echocardiography, there is dilation of one or both ventricles with poor function. A CCO <400 mL/kg/min indicates insufficient compensation, suggesting severe disease with poor outcome. Pericardial effusion may be present, especially if there is an infectious etiology. Increased filling pressures are marked by fusion of AV valve inflow E and A waves, flow reversal in the ductus venosus with atrial contraction, and umbilical venous pulsations. If there is inadequate cerebral perfusion due to poor cardiac function, the cerebral vasculature will vasodilate to improve flow to the brain. As a result, the ratio of middle cerebral artery pulsatility index to umbilical artery pulsatility index will decrease and eventually reverse. Lastly, the Cardiovascular Profile Score can be used in the assessment. Serial monitoring is certainly indicated in these unique patients.

Management and outcomes in DCM in the fetus depend on the underlying etiology of the disease process. Maternal autoimmune disorders can be treated with anti-inflammatory steroid treatment to preserve myocardial function. Digoxin can also be utilized as it crosses the placenta easily and improves heart function and hydrops. Prognosis for fetuses diagnosed with DCM is typically poor. One series demonstrated a survival rate of 50% for non-hydropic fetuses and an 18% survival rate for hydropic fetuses. ¹¹² Postnatally, cardiac transplant can be considered if function fails to improve in the setting of heart failure.

Hypertrophic cardiomyopathy

Concentric or septal thickening of the fetal heart without an underlying structural cardiac defect can lead to heart failure and hydrops. In some cases, septal thickening occurs first, resulting in LV outflow tract obstruction thereby prompting further thickening of the ventricle. There are several different underlying etiologies of hypertrophic cardiomyopathy in the fetus. Noonan’s syndrome is an autosomal dominant disorder caused by a variety of heterogeneous mutations, including PTPN11, KRAS, SOS1 and RAF1 genes, resulting septal and ventricular free wall hypertrophy. LEOPARD syndrome is a cause of HCM in the fetus and is another autosomal dominant disorder that is associated with mutations on the PTPN11 gene. This disorder is associated with additional skin, skeletal, sensori-neural abnormalities. Fetal HCM is found in families with HCM and genetic testing for the specific mutation may be available.

Maternal diabetes mellitus is a major contributor to the make-up of HCM seen in the fetus. This hypertrophy can progress over the course of gestation until delivery. There is worse hypertrophy with poor glucose management, however changes in the myocardium can be seen despite excellent diabetic control. Most cases of HCM are not obstructive and will resolve after birth over the course of several weeks. In addition to the risk of HCM in this patient population, there is an increased risk of birth defects up to 2–10 times greater than that of normal pregnancies and an increased incidence of structural heart defects, including double outlet right ventricle and transposition of the great arteries.¹¹³

On fetal echocardiography, M-mode can be used to measure septal thickening. Flow across the left ventricular outflow tract of greater than 1.2 m/s is abnormal and may be seen in addition to the finding of mitral regurgitation. Increased nuchal translucency with normal karyotype in the first trimester with ventricular thickening in the second trimester suggests a diagnosis of Noonan’s syndrome. HCM in Noonan’s syndrome may also be associated with cystic hygroma and pleural effusions. In Type 1 diabetic pregnancies, diastolic dysfunction may be seen prior to gross changes in myocardial thickness.¹¹⁴ Lower E/A ratio and longer isovolumetric relaxation time, resulting in higher left MPI, can be seen in these fetuses. HbA1C is directly proportional to the degree of septal hypertrophy and inversely related to cardiac performance.¹¹⁵ Fetuses of mothers with DM should be evaluated at 20–24 weeks and follow-up is indicated if the fetal echocardiogram is abnormal or if glucose control is poor.

Fetal arrhythmia

Atrial and ventricular tachyarrhythmias, as well as complete heart block, are dysrhythmias that can result in fetal heart failure, hydrops and demise. The primitive heart tube begins rhythmic pulsations within 3 weeks after conception, however the conduction system does not fully mature until the second trimester. It is estimated that 1–3% of pregnancies have a rhythm disturbance.¹¹⁶ Ten percent of these rhythm disturbances are life threatening, while 90% are benign, transient arrhythmias. Assessment of the atrium and ventricle together enables fetal cardiologists to evaluate for rhythm disturbances using M-mode, tissue Doppler imaging, and Doppler flow patterns. Fetal magneto cardiography provides information similar to that of a fetal electrocardiogram, however requires specialized equipment with limited availability. Fetal arrhythmias can lead to heart failure through a variety of mechanisms. In tachyarrhythmias there is poor cardiac output due inadequate filling time during tachycardia and impaired myocardial perfusion due to oxygen supply/demand mismatch. In bradyarrhythmia, low heart rate limits cardiac output when increase in stroke volume cannot compensate. In both fast and slow rhythms, cardiomyopathy may be associated.

Therapy for tachyarrhythmias may include antiarrhythmic agents such as digoxin, sotalol, flecainide and amiodarone. Meanwhile, steroids, hydroxychloroqine and beta-agonists are medications that may be used for fetal bradyarrhythmias such as complete heart block.

Structural congenital heart disease

Various forms of structural congenital heart disease (CHD) can lead to congestive heart failure and hydrops fetalis. Valvar regurgitation, outflow tract obstruction, and ventricular dysfunction are often features of CHD that can lead to poor outcomes. Severe atrioventricular and semilunar valve regurgitation may lead to heart failure and congenital heart defects associated with these valvar abnormalities include Ebstein’s anomaly, Tetralogy of Fallot with absent pulmonary valve, pulmonary atresia with a dysplastic tricuspid valve, and truncus arteriosus with severe truncal valve regurgitation. ¹¹⁷ Bilateral outflow tract obstruction may also lead to impaired cardiac output and congestive heart failure. At this time there are few safe and effective options for these patients in fetal life, but advances in fetal interventions, such as aortic balloon valvuloplasty, may offer potential benefits in the future. Delivery with access to postnatal intervention remains an option after weighing the risks and benefits of prematurity in the setting of congenital heart disease.

Conclusions

A myriad of conditions may cause fetal heart failure, each with a unique pathophysiology. Our current utilization of fetal echocardiography provides an excellent means for assessing the impact of these various conditions on the fetal circulation. With continued application of fetal echocardiography will come continued improvement in the care and management of these complex conditions, and improved outcomes.