(Bright Papillary Muscle)
A bright echogenic focus is seen in these two cases of varying size and reflection. Both are seen in the left ventricle and were not associated with a mass or cardiac malformation. Additonally, both fetuses were normal at birth.
A bright echogenic focus, usually in the left ventricle was described in 1987 as being due to a reflection of the papillary muscle or chordae tendinae. It was seen in 20-22% of patients and was a normal finding in these patients. The more frequent location in the left ventricle was thought to be due to the larger size of the left ventricular papillary muscle. When a mass is seen associated with either a bright focus or calcification, a tumor ie rhabdomyoma or teratoma should be considered.
In 1995, the association of a bright echogenic focus and Down syndrome was made. A fourfold increased risk of Down syndrome was associated with a bright echogenic intracardiac focus. In the series reported, the positive predictive value of an echogenic intracardiac focus for detecting Down syndrome in patients with an age-based risk of one in 250 was 1.53%. A pathologic study by Roberts and Genest in 1992 found papillary muscle calcification in 16.5% of fetuses with Trisomy 21 and 38.9% of fetuses with Trisomy 13. Another, more recent study, evaluated the association of an echogenic cardiac focus and fetal and neonatal abnormalities. These authors found an incidence of 4.9% in their study population. In their study the authors had no patients with features of aneuploidy.
A recent study by Achiron et al evaluated 2214 low-risk patients who had ultrasound evaluations at 13-16 weeks transvaginally and a follow-up transabdominal scans at 20-22 weeks gestation. As part of a thorough examination the presence of echogenic foci within the heart were noted. Echogenic foci within the heart were found in 163 cases (7.4%) during the transvaginal scans performed at 13-16 weeks gestation. At 20-22 weeks gestation only 66 cases demonstrated echogenic foci within the fetal heart. In 75% of cases the echogenic foci was in the left ventricle; 4.9% of cases had bilateral findings. Sixteen fetuses had karyotyping, all of which was normal. The remaining 97 fetuses were all phenotypically normal at birth. In addition all neonatal echocardiograms done on this patient population were normal. These authors, in an attempt to estimate the likelihood of an association between these foci and trisomy 21, reviewed the literature. They found 489 cases of echogenic foci among 37,498 fetuses that were screened. Among the 489 cases there were six cases with trisomy 21. Correlating this data with the prevalence of these foci and the prevalence of trisomy 21 in the general population the authors calculated the expected risk of trisomy 21 in cases of isolated fetal cardiac echogenic foci to be 0.002%. This is obviously far below the risk of trisomy 21 in a 35 year old woman or the risk of loss from amniocentesis. In the recent 13th International Congress "The Fetus as a Patient" (Basel, Switzerland, June, 1997) two papers were presented with evaluation of fetal echogenic cardiac foci. In the study by Bettelheim et al the authors detected 35 cases of echogenic foci from 2,200 patients (1.6%). A normal karyotype was present in all patients. In the second study by Kahler et al, 747 patients referred for a level II sonogram were evaluated and 62 cases of echogenic intracardiac foci were seen (8.3%). One fetus had an abnormal karyotype (47 XXY) without further sonograpic abnormalities. 12 fetuses with normal karyotype showed further sonographic findings: bi and unilateral pyelectasis, choroid plexus cysts, single umbilical artery, echogenic bowel and intrauterine growth retardation. Two fetuses died in utero. All echocardiographic evaluations were normal in their patients. They concluded that karyotyping and "detailed counseling" should be offered to these patients.
A report by Bromley et al was based upon a prospective evaluation of 290 fetuses over a 1 year period in which an echogenic focus was detected and follow-up was obtained. At sonography 125 women were aged 35 years or older and 165 women were younger than 35 years. Of the 290 patients, 14 fetuses were aneuploid (4.8%). Of these 11 were trisomy 21, 1 was trisomy 13, 1 was triploidy, 1 Turners syndrome. Of women 35 years or older 8 were aneuploid (6.4%), while of the 165 women 34 years or younger there were 6 aneuploid fetuses (3.6%). Of interest, only one of 14 fetuses with aneuploidy had an echogenic cardiac focus as the only sonographic finding (patient was 41 years old). 13 of the 14 fetuses with aneuploidy had multiple anomalies including : increased nuchal fold, pyelectasis, short extremities, heart abnormalities, ventriculomegaly, echogenic bowel, etc. In virtually every case the additional abnormalities would likely be noted during routine scanning.
The majority of the echogenic intracardiac foci were located within the left ventricle (254 of 290 fetuses - 87.6%). There were 14 fetuses (4.8%) having a right sided only focus and 22 fetuses (7.6%) having an echogenic focus in both ventricles. Eleven (11) of the 254 fetuses (4.3%) with left sided echogenic foci were aneuploid, whereas combining right sided and bilateral foci together; 36 fetuses (8.3%) were aneuploid.
This study adds to our knowledge of the impact of the finding of an echogenic intracardiac focus and its association with aneuploidy. As with many other reported sonographic findings that are clues to aneuploidy; an important issue is whether there are associated findings. Eight of the 13 fetuses with other findings had nuchal folds or cystic hygromas. The remaining 5 fetuses had either echogenic bowel, ventriculomegaly, encephalocele or cystic kidneys or IUGR. All of these findings would be likely detected on a routine (non-survey type) exam. In women with an echogenic intracardiac focus as the only finding the risk of aneuploidy decreased from 6.4% to 0.8% (35 yrs or greater) and 3.6% to 0% (younger than 35 years).
In a recent study, Wax et al performed a literature search from 1980 to 1997 to evaluate the significance of fetal intracardiac echogenic foci. "Studies were excluded because of indeterminate intracardiac echogenic foci laterality, evaluation of intracardiac echogenic foci not being the primary objective or fetal chromosomal and structural heart defects not having been discussed." Nine studies met inclusion criteria. The authors literature search revealed demonstrated intracardiac echogenic foci in 0/17% to 20% of fetuses.
Aneuploidy was noted in 10 of 217 fetuses with left ventricular intracardiac echogenic foci and one of 18 fetuses with right ventricular intracardiac echogenic foci . 3 of 11 fetuses with biventricular intracardiac echogenic foci were aneuploid. Structural cardiac abnormalities were identified in 8 of 217 fetuses with left ventricular intracardiac echogenic foci, 2 of 18 with right ventricular intracardiac echogenic foci and one of 11 with biventricular intracardiac echogenic foci. 6 of 11 fetuses with intracardiac echogenic foci and structural heart abnormalities were aneuploid. 10 of 14 fetuses (71%) with intracardiac echogenic foci and autosomal trisomies (all cases of trisomies 13 and 18) had additional ultrasonographically detected anomalies. In addition, 5 of 11 fetuses with intracardiac echogenic foci and structural heart abnormalities had other non-cardiac abnormalities detected by ultrasound.
The authors review the commonly sited explanations for intracardiac echogenic foci including incomplete fenestration of the endocardial tissue and variable excavation of the myocardium during papillary muscle formation. The authors discuss reasons for the variable prevalence and associations of intracardiac echogenic foci including: different definitions and subjectivity for determining echogenicity, sonographic instrumentation and settings, populations sampled for study, fetal gestational ages at examination, performance of fetal or neonatal echocardiography or both, availability and completeness of neonatal follow-up, and overall research design. They appropriately caution that these factors should be considered before reaching a conclusion regarding prevalence or associations with either aneuploidy or structural abnormalities.
A recent excellent review of the cardiac echogenic focus appeared in Prenatal Diagnosis by J. Simpson. The author reviews the current knowledge and controversy concerning the intracardiac echogenic focus. The finding of an intracardiac echogenic focus within the ventricles of the fetal heart was first described in the mid-1980s (Allan, 1986; Schechter et al., 1987, 1988; Levy and Mintz, 1988). As the author states "These echogenic foci have also been referred to as 'golf balls' or 'peas'. Initially, such appearances were thought to be entirely benign (Levy and Mintz, 1988). Since then, the significance of such lesions has become more controversial, because some data suggest an association with fetal karyotypic abnormalities.An echogenic focus may be defined as a discrete area within the cavity of either ventricle of the heart, the echogenicity of which is similar to that of fetal bone. In 1992, Roberts and Genest (1992), described the histology of the myocardium in fetuses with trisomy 21 and trisomy 13, and compared the findings with karyotypically normal human fetuses. Calcification of the papillary muscles was observed in 2 per cent of normal fetuses, 16 per cent of fetuses with trisomy 21 and 39 per cent of fetuses with trisomy 13. More recently, three fetuses have been described in whom an echogenic focus was detected antenatally, and in whom mineralization of the papillary muscle was confirmed at autopsy (Brown et al., 1994). It has been suggested that echogenic loci represent failure of the chordae tendinae to fenestrate during prenatal development (Schechter et al., 1987), but there are no pathological data to support this contention. The reported incidence of echogenic foci varies widely from series to series. The lowest reported incidence was 0.13 per cent (Bronshtein et al., 1996) and the highest was 20 per cent (Levy and Mintz, 1988). Most series have reported an incidence between 3 per cent and 8 per cent (Dildy et al., 1996 (4.9 per cent); Simpson et al., 1996 (6.9 per cent); Schechter et al., 1987 (3.5 per cent); Bromley et al., 1995 (4.9 per cent); Achiron et al., 1997 (7.4 per cent)). The variability in incidence may reflect such factors as referral population, the timing of scanning, fetal position and image quality. At 13-16 weeks' gestation, Achiron et al. (1997) documented the presence of an echogenic focus in 163 fetuses from a screened population of 2214, giving an incidence of 7.4 per cent. When echocardiography was repeated at 2022 weeks' gestation, 60 per cent of echogenic foci could not be visualized. Echogenic foci may be single or multiple. The most common finding is that of a single focus in the left ventricle, which accounts for around 6090 per cent of cases (Simpson et at., 1996; Bromley et at., 1998). One large series documented an isolated echogenic focus in the left ventricle in 60 per cent of cases, multiple foci in the left ventricle in 16 per cent, bilateral echogenic foci in 16 per cent and echogenic foci limited to the right ventricle in 7 per cent (Simpson et at., 1996). It has been suggested that echogenic foci are more frequent in the left ventricle than the right because of the relatively larger size of the papillary muscles in the left ventricle, but this remains speculative.
The relationship of single or multiple echogenic foci to karyotypic abnormalities is extremely controversial. In an early report describing the echogenic focus (Schechter et at., 1987), 1 of 26 fetuses had trisomy 21, and 1 of the 3 fetuses described by Brown et at. (1994) had trisomy 21. This, together with the pathological data (Roberts and Genest, 1992), led to the suggestion that the echogenic focus should be regarded as a sonographic marker for fetal Down syndrome. This is supported by studies which have demonstrated an increased incidence of echogenic foci in fetuses with trisomy 21 compared with karyotypically normal fetuses (Bromley et at., 1995). Many reported series include patients who are at high risk for chromosomal abnormalities, either because of prior risk factors such as raised maternal age, or because of coexisting sonographic abnormalities, and in whom fetal karyotyping was under consideration irrespective of the finding of single or multiple echogenic foci. A more difficult question is the risk of chromosomal abnormalities in fetuses with echogenic foci and no other risk factors. Contrary to the evidence presented above, some reports have suggested that cardiac echogenic foci are not associated with karyotypic abnormalities and should be regarded as a normal variant. How et at. (1994) reported no case of trisomy 21 among 25 patients with an echogenic focus and Petrikovsky et at. (1995) reported no karyotypic abnormalities among 41 such cases. More recently, Achiron et at. (1997) performed an analysis of eight separate reported series of echogenic foci. Echogenic foci were identified in 489 fetuses, who were drawn from a screened population of 37 498. They assumed that the background prevalence of trisomy 21 was 1:600, and that 16 per cent of fetuses with trisomy 21 would have echogenic foci. Using these assumptions, they calculated a 0.002 per cent risk of trisomy 21 for women below the age of 35 with isolated echogenic foci. This, they concluded was below the risk for which they would recommend fetal karyotyping. These authors' assumed incidence of echogenic foci in trisomy 21 was, however, based on pathological rather than echocardiographic data and the estimated population incidence of trisomy 21 may not be generally applicable. Clearly, an estimation of an individual patient's prior risk of Down syndrome based on age and other investigations, such as nuchal translucency, will be crucial to the interpretation of the results of future series. Recent work does suggest that the location and number of echogenic foci may influence the risk of karyotypic abnormality. In the study of Bromley et at. (1998), there was a trend towards bilateral echogenic foci being more strongly associated with aneuploidy."
More studies are needed to conclusively add this to the list of unequivocal sonographic abnormalities that are associated with karyotypic abnormalities. At the present time the findings are controversial and should likely wait for more convincing data before amniocentesis can be recommended in all patients with this finding. Of note, one must be careful not to assign this diagnosis to a specular reflection from the valve surface.
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Professor of Radiology, Obstetrics, Gynecology and Reproductive Science
University of California Medical Center, San Francisco, California