Cardiomyopathy refers to cardiac hypertrophy manifested by an increased interventricular septal size and/or free ventricular wall size in the absence of an increased cardiac load, accompanied by decreased cardiac function and by ventricular dilation (Michels et al., 1992). More broadly, cardiomyopathy is defined as a disease of the myocardium characterized by the presence of systolic or diastolic dysfunction or abnormal myocardial structure (Schwartz et al., 1996). The condition is rarely observed during fetal life. Cardiomyopathy is generally classified as dilated or hypertrophic.

The incidence of fetal cardiomyopathy is not precisely known, but it is rare. In one study, dilated cardiomyopathy was present in approximately 2% of fetal cardiac abnormalities (Sivasankaran et al., 2005).

Relatively recently, two large-scale population-based cohort studies of cardiomyopathy in children were published. One was performed in Australia (Nugent et al., 2003) and one involved American children in New England and the Central Southwest (Lipshultz et al., 2003). In the Australian study, the incidence of cardiomyopathy was 1.24 per 100,000. Of these, 58.6% had dilated cardiomyopathy, 25.5% had hypertrophic cardiomyopathy, 9.2% had cardiomyopathy due to noncompaction of the left ventricle, and 2.5% of cases were restrictive. There was a large familial component (19.8% of cases). Indigenous children had a 2.67-fold relative risk of having the disease compared to nonindigenous children. The American study showed a similar incidence (1.13 per 100,000) and identified a peak incidence in the first year of life. In this study, 51% of cases were due to dilated cardiomyopathy, 42% to hypertrophic, 3% to restrictive, and 4% to unspecified. The American study noted a higher incidence in black children. Both studies documented a higher incidence in males, presumably due to the X-linked conditions that are associated with cardiomyopathy, such as Duchenne, Becker, and Barth syndromes.

Relatively few reports of the prenatal diagnosis of fetal cardiomyopathy exist. One of the most comprehensive encompasses a 9-year retrospective review of fetuses studied in the Fetal Cardiac Program at the Hospital for Sick Children in Toronto (Pedra et al., 2002). This study reported on 55 affected fetuses. Evaluation included a complete two-dimensional study, spectral Doppler, and color flow mapping. The authors measured cardiothoracic ratio, left and right ventricular end-systolic and end-diastolic diameters, and wall thickness. Measurements in affected pregnancies were compared with values obtained in 55 normal fetuses. Ventricular systolic and diastolic function was assessed. Dilated cardiomyopathy was diagnosed in the presence of systolic dysfunction with or without significant chamber enlargement but without wall thickening. Hypertrophic cardiomyopathy was diagnosed when the ventricular wall thickness was ≥2 SD above the normal mean for gestational age, with or without ventricular systolic or diastolic dysfunction (Pedra et al., 2002).

Although the incidence of hypertrophic cardiomyopathy in the Pedra et al. (2002) study was higher than dilated cardiomyopathy, the numbers are affected by two reasonably common conditions, maternal diabetes and twin–twin transfusion syndrome (see Chapter 119). A significant body of literature exists on the fetal heart in the offspring of the diabetic mother. Gutgesell et al. (1980), studied 47 infants of diabetic mothers by echocardiography. In this study, 24 of the infants were clinically symptomatic. Five had marked septal hypertrophy with echocardiographic features that suggested left ventricular outflow obstruction. Five infants had hypertrophy of the right ventricular free wall. One symptomatic infant died from an unrelated bacterial infection. In the clinically asymptomatic infants, three were shown to have septal hypertrophy, two had right ventricular free wall hypertrophy and no patients had left ventricular outflow obstruction. None of the patients in the entire study had evidence of dilated or congestive cardiomyopathy, and all patients had resolution of their echocardiographic abnormalities during the first 6 months of life. This was the first report to suggest the use of echocardiography to follow cardiac changes occurring in infants of diabetic mothers. The alterations in the hearts of infants of diabetic mothers were shown to be due to an increased mass of myocardial nuclei and sarcoplasm, but they were self-limited.

Subsequently, fetuses in mothers who had wellcontrolled type I insulin-dependent diabetes were studied at 4-week intervals between 20 and 30 weeks of gestation by M-mode and Doppler echocardiographic studies (Rizzo et al., 1992). These investigators measured intraventricular septal thickness, left and right ventricular wall thickness, and the ratio between the peak velocities during the early passive ventricular filling and active atrial filling at the level of the atrioventricular valves. They also studied peak velocities and time to peak velocity at the level of the ascending aorta and pulmonary artery. The findings in the 14 fetuses of diabetic mothers were compared with those in 10 normal control fetuses. This study revealed that all indices investigated increased linearly with advancing gestation. The fetuses of the diabetic mothers showed an accelerated increase in cardiac size occurring during the late second trimester, manifested by progressive thickening of the intraventricular septum and ventricular walls. These investigators demonstrated that strict control of maternal diabetes did not prevent the accelerated fetal cardiac growth and abnormal development of cardiac function, which was mainly manifested by impaired diastolic function (Rizzo et al., 1992). The study was followed by a related report that compared fetal echocardiographic indices in fetuses of mothers with well-controlled insulin-dependent diabetes to normal fetuses during the second and third trimester (Gandhi et al., 1995). An increase in right ventricular shortening fraction was associated with global cardiac enlargement, which did not adversely affect myocardial contractility. These authors hypothesized that metabolically stable maternal diabetes may be associated with a mild but definite myocardial hypertrophy that affects the growth of the ventricular and septal walls (Gandhi et al., 1995). The echocardiographic changes associated with maternal diabetes are not, strictly speaking, a cardiomyopathy, but rather a self-limited cardiac hypertrophy. Only in extremely rare cases does the maternal diabetes result in systolic or diastolic cardiac dysfunction, progressing to congenital heart failure.

Prenatal sonographic manifestations of familial hypertrophic cardiomyopathy are increasingly being appreciated. In one report, a 25-year-old primigravida was described with hypertrophic apical cardiomyopathy whose fetus had normal echocardiographic examinations at 19 and 21 weeks of gestation. At 27 weeks of gestation, two-dimensional and M-mode echocardiograms revealed a generalized fetal cardiac hypertrophy with a markedly thickened intraventricular septum. This was confirmed at 32 and 36 weeks of gestation but did not worsen throughout the rest of the pregnancy. The patient was studied postnatally and followed to age 15 months, when stable cardiac hypertrophy was observed (Stewart et al., 1986).

Genetic syndromes, such as Noonan syndrome, can present with hypertrophic cardiomyopathy. In one case report, a fetus with cystic hygroma and a normal karyotype, diagnosed postnatally with Noonan syndrome, was referred for fetal echocardiography at 23 weeks of gestation. A small primum atrial septal defect, increased echogenicity of the mitral valve, and modest hypertrophy of both ventricles were observed (Sonesson et al., 1992). In the same fetus, observed serially at 35 weeks of gestation, prominent hypertrophy of both ventricles was demonstrated. Retrospectively, these authors noted that the first sign of myocardial abnormality was observed in the diastolic filling of both ventricles. However, this may be a subtle finding, as all fetuses have different diastolic filling velocities compared with newborn infants.

In a retrospective review of six cases of fetal dilated cardiomyopathy, Schmidt et al. (1989) made a sonographic diagnosis by numerous approaches, including the four-chamber, long-axis, short-axis, and aortic-arch views. Prenatal sonographic imaging was complemented by M-mode echocardiography for better definition of the motion patterns of the atrioventricular and semilunar valves (Schmidt et al., 1989). This group defined the right and left ventricular fractional shortening (FS) index as:

FS = (EDD – ESD) x 100/EDD,

where EDD is the end-diastolic diameter of the ventricle and ESD the end-systolic diameter of the ventricle. These investigators demonstrated that in five of the affected fetuses, the right ventricular FS index was less than 2 SD below the normal mean for gestational age, and in four, the left ventricular FS index was less than 2 SD below the normal mean. In addition, they observed significantly larger mean end-diastolic diameters. In affected fetuses, the FS decreased progressively during gestation while the chamber enlargement increased (Schmidt et al., 1989).

The most important consideration in the differential diagnosis is to determine whether the cardiomyopathy is dilated or hypertrophic (Table 57-1). In dilated cardiomyopathy, the ventricle is thin-walled and dilated; mitral and or tricuspid regurgitation is also present (Figures 57-1 and 57-2). In the study performed at the Hospital for Sick Children (Pedra et al., 2002) 22/55 fetuses had dilated cardiomyopathy and 33 hadhypertrophic. The various causes of the dilated cardiomyopathy were endocardial fibroelastosis (6 cases), familial (5), cytomegalovirus infection (2), and idiopathic (9). The underlying diagnosis in the hypertrophic cases included: twin–twin transfusion (18 cases) (Figure 57-3), maternal diabetes (7), Noonan syndrome (2), alpha thalassemia (2), familial (1), and idiopathic (3).