Fetal Cardiology

Transposition of the great arteries: Fetal pulmonary valve growth and postoperative neo-aortic root dilatation.

van der Palen RLF, van der Zee C, Vink AS, Knobbe I, Jurgens SJ, van Leeuwen E, Bax CJ, du Marchie Sarvaas GJ, Blom NA, Haak MC, Bilardo CM, Clur SB. Prenat Diagn. 2019 Jul 27. doi: 10.1002/pd.5539. [Epub ahead of print]   Take Home Points: Neoaortic root dilation is common and occasionally needs intervention in patients born with transposition of great arteries (TGA) who underwent an arterial switch operation. In this longitudinal study of semilunar valve size in fetal TGA subjects, semilunar valve diameters are larger than in the normal fetus, especially in those with TGA and VSD. Prenatal pulmonary valve size at 26 to 30 weeks determines neoaortic root size after arterial switch procedure in patients with TGA. Commentary from Dr. Shaji Menon (Salt Lake City), section editor of Pediatric Cardiology Journal Watch: This is a retrospective multicenter observational study of 137 fetuses with TGA; 36% with ventricular septal defects.  Arterial switch operation was performed in 121 subjects.  Fetal semilunar valve diameters were significantly larger than control aortic valve diameters, especially in patients with VSD.  There was positive correlation between Z‐scores of fetal TGA pulmonary valve at 26 to 30 weeks and neoaortic valve diameter at last follow‐up (P < .001).

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Fetal cardiac findings and hemodynamic changes associated with severe lower urinary tract obstruction in utero.

Fetal cardiac findings and hemodynamic changes associated with severe lower urinary tract obstruction in utero. Cohen J, Levasseur S, Simpson L, Miller R, Freud L. Ultrasound Obstet Gynecol. 2019 Dec;54(6):780-785. doi: 10.1002/uog.20271. Epub 2019 Nov 4. PMID: 30908816 Similar articles   Take Home Points: Fetuses with lower urinary tract obstruction (LUTO) have a shorter indexed mitral valve inflow time and higher left ventricular myocardial performance index suggesting left ventricular dysfunction. LUTO fetuses had higher right ventricular to left ventricular cardiac index ratio, which might explain the finding of smaller left-heart structures in a subset of fetuses with LUTO.   Commentary from Dr. Inga Voges (Kiel, Germany), section editor of Pediatric Cardiology Journal Watch:  Fetuses with lower urinary tract obstruction (LUTO) can develop cardiomegaly, cardiac hypertrophy and pericardial effusion. In this interesting retrospective study, the authors analyzed echocardiograms of a cohort of 25 fetuses with LUTO with a focus on ventricular function and hemodynamic assessment. 25 gestational age (GA)-matched control fetuses were included. Five patients had serial postnatal echocardiograms, that were analysed.   Fetuses with LUTO commonly presented with cardiomegaly, pericardial effusion as well as right and left ventricular (RV, LV) hypertrophy demonstrated by increased LV, RV and septal wall thickness. Six Fetuses had right ventricular dysfunction and four fetuses had small left-heart structures.   Myocardial performance index was significantly increased, and mitral valve inflow time indexed to cardiac cycle length was significantly reduced, both suggesting LV diastolic dysfunction. RV cardiac index was higher, and LV cardiac index was lower compared to controls, resulting in an increased RV to LV cardiac index ratio in LUTO fetuses. Ascending aortic and aortic isthmus z-scores were lower in LUTO fetuses compared to controls. See Table 2 and Figure 1.   During follow-up there were 17 liveborn patients; two of the 25 pregnancies were lost to follow-up, three had elective termination of pregnancy and there was intrauterine fetal demise in three cases.   One out of the four fetuses with small left-sided structures demised in utero. Two of the remaining three fetuses presented with slightly small left-sided structures postnatally that did not require any intervention, the third one was diagnosed with coarctation and died a few hours after birth due to respiratory distress. In those patients with serial postnatal echocardiograms, systolic function normalized by 3–10 days and ventricular hypertrophy normalized by 20 days to four months.   The authors nicely explain possible reasons for their finding of small left-heart structures (Figure 2) and hereby motivate others to perform future studies.         

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Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta.j

Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta. Vigneswaran TV, Zidere V, Chivers S, Charakida M, Akolekar R, Simpson JM. Ultrasound Obstet Gynecol. 2019 Dec 25. doi: 10.1002/uog.21957. [Epub ahead of print] PMID: 31875324   Take Home Points:  Prenatal diagnosis of coarctation may be improved with routine measurement of the distal transverse arch and ductus arteriosus from the 3 vessel view There is a high incidence of bicuspid aortic valve in patients with suspected, but not proven to have, coarctation.   Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch:  Prenatal diagnosis of coarctation of the aorta (COA) is known to be quite difficult, with frequent false positives. There have been quite a few studies assessing various measurements to try to improve the diagnostic accuracy, but most are retrospective. It is known that prenatal diagnosis will improve morbidity and mortality, but false positives can have a negative psychological effect on the parents as well as prevent the initial infant/maternal bonding after birth.   This study  looked at cases of suspected COA between 15-36 GA who had at least 6 months of postnatal follow up, and who did not have any other major CHD. They used data from the time of the study (with the data set closest to 20 weeks GA to compute z-scores in patients with multiple studies). They measured the aortic and pulmonary valves in diastole at the maximal diameter, and the distal transverse aortic arch diameter (DTAA) and arterial duct (AD) in the 3 vessel view (3VT). They converted all measurements into z-scores that were derived from their own previously published data on 7000 normal fetuses. Of the 149 fetuses included in this study, 52% were confirmed to have COA within 6 months of age (most diagnosed in the neonatal period). Bicuspid aortic valve was identified after birth in 57% of the true COA group and 30% of the false positive group. A VSD was seen in both true and false positive cases. While aortic:pulmonary valve diameter ratio, DTAA diameter, 2nd trimester DTAA:AD ratio, AV z-score, DTAA z-score, and 2nd trimester z-score of the ratio of DTAA:AD were significantly smaller in the true COA group (see Table 1), logistic regression demonstrated that DTAA z-score and AD z-score were the only predictive variables. Table 3 shows the ROC curves for all variables and table 4 shows the sensitivity, specificity, PPV and NPV of the DTAA z-score.   A clear cut-off value for both DTAA z-score and the ratio were not provided, most likely given there is some overlap with a continued reasonably high (but better) false positive rate even when adding these measurements to the other published measurements in suspected COA. While a risk equation calculation was provided, lack of good cut-off values make it difficult for the individual sonographer and cardiologist to make decisions in real time based on their measurements. A few interesting features of the study include only using 3 vessel view measurements and not the sagittal aortic arch view, as well as the high frequency of BAV in the suspected COA group, which should likely affect prenatal counseling and should warrant further study.       

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Feasibility of Non-invasive Fetal Electrocardiographic Interval Measurement in the Outpatient Clinical Setting.

Doshi AN, Mass P, Cleary KR, Moak JP, Funamoto K, Kimura Y, Khandoker AH, Krishnan A. Pediatr Cardiol. 2019 Jun 6. doi: 10.1007/s00246-019-02128-w. [Epub ahead of print] PMID: 31172229 Similar articles Select item 31172686   Take Home Points: Fetal EKG scanning in a routine clinical setting may be feasible. Further research, automation, and assessment of cost effectiveness will likely be necessary. Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch:  As most fetal cardiologists know, an easy way to obtain a fetal EKG could be a holy grail for diagnosis and management of fetal arrhythmias and possibly prevention of hydrops and fetal demise. While echocardiography can indirectly assess certain rhythm abnormalities, measurement of the QRS complex or QT interval is not possible. There have been past attempts for obtaining a fetal EKG, but the ability to extract the low amplitude fetal signals from the maternal abdominal signals has been poor. Fetal magnetocardiography is currently the gold standard for assessment of fetal arrhythmias, but this is limited to a few large centers that have the equipment necessary for this. This study group used equipment that utilizes blind source separation, a novel signal processing technique that has been shown useful to obtain low amplitude signals and is not dependent on precise electrode positioning. Their objective was to determine the feasibility of measuring standard EKG intervals.   55 fetuses (with a few twin gestations) were studied after 5 were removed from analysis due to a non-functional signal amplifier. Gestational age (GA) ranged from 18-37 weeks (median 23). There were 13 during the vernix period (weeks 25-32), a period known to present difficulty in fetal EP analysis due to the electrical insulating properties of the vernix caseosa, the waxy coating of the fetal skin most prominent at that time. 10 minutes of data were recorded using a prototype fetal EKG monitor using blind source separation as described in a previous paper. Specialized electrodes were placed on the maternal abdomen with one additional electrode on the back as a reference and one on the upper chest to capture the maternal EKG. A magnetic interference shield was draper over the mother and all electrodes were connected to a signal amplifier. Averaged fetal EKG waveforms were processed off-line (see paper for description). Post-processing time was reported as taking between 5-30 minutes, shorter in normal patients, longer in those with rhythm abnormalities (see figure 2).   50 of the 55 fetuses had interpretable results (91%), with 11/13 (85%) in the vernix period. Figure 3 shows the median and interquartile ranges of the EKG intervals at each gestational group. 6 fetuses had abnormal rhythms on fetal echo, and fetal EKG tracings were able to be obtained from 5 of 6, all of which demonstrated the same rhythm abnormality. The authors report that their fetal EKG interval values were similar to those reported when using fetal magnetocardiography.   This was an interesting feasibility study. While the authors report relatively quick and ease of interpretation of the fetal EKG, this would need to be confirmed in larger and more diverse clinical setting before widespread use could be considered. Additionally, how this data will impact clinical management would need to be further elucidated.    

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Usefulness of Postnatal Echocardiography in Patients with Down Syndrome with Normal Fetal Echocardiograms.

Cooper A, Sisco K, Backes CH, Dutro M, Seabrook R, Santoro SL, Cua CL. Pediatr Cardiol. 2019 Sep 20. doi: 10.1007/s00246-019-02209-w. [Epub ahead of print] PMID: 31541264 Similar articles Select item 31568264   Take-Home Points: The incidence of significant congenital heart defects(CHD) on postnatal echocardiograms for patients with Down Syndrome (DS) who had a normal fetal echo is nearly zero. Minor CHD, if present, will likely have an abnormal exam or EKG finding. Delivery at a center without pediatric cardiology availability is likely reasonable. Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch:  A fetal echocardiogram is a class I recommendation if a chromosomal abnormality is present. The AHA currently recommends a postnatal echocardiogram in all patients with DS regardless of a normal fetal echocardiogram. With a new emphasis on appropriate use criteria in pediatric echocardiography, this may be a subgroup that could be further evaluated. The primary and secondary goals of this study was to determine if there was any missed complex CHD and any CHD postnatal echocardiograms after a normal fetal echo in DS patients. This was a retrospective evaluation of 120 total patients with suspected DS; 72 had complex CHD with the most common diagnoses AVSD and VSD. 45 patients had a normal fetal echo and also had a postnatal echo performed. Complex CHD was defined as a diagnosis with RACHS >/= 3.  PFO and PDA were not included as pathologic CHD diagnoses for the purpose of this study. The gestational age at the time of initial fetal echo was 25 +/- 3.5 weeks. The median age at postnatal echo was 7 days, with 24 patients having an echo within the first week of life. No patients had complex CHD; negative predictive value was 100%. 13 patients had minor CHD consisting mostly of ASDs or VSDs; negative predictive value 71.1%.  All of them had a heart murmur or EKG abnormality on evaluation. 1/13 patients died from severe PPHN. 3/13 required intervention (2 caths for PDA closure, 1 primum ASD repair). One other patient has a primum ASD that was still being followed (see table 1). While fetal echocardiography does not have 100% sensitivity for ruling out CHD, this study adds weight to previous studies that missed complex CHD is very unlikely. At a minimum, in an otherwise uncomplicated pregnancy or in a region with many hospitals that do not have direct access to pediatric cardiology, it would seem quite reasonable to deliver patients with a negative fetal echo and refer them to pediatric cardiology within the first few weeks of life. There is unlikely enough evidence to change the postnatal echo recommendations given that there are many minor CHD diagnoses that need to be followed over time; however, the authors do speculate how AUC may be used in this population when adding other historical and clinical factors and an EKG. Limitations of this study include its small sample size and retrospective design, but this study could easily be replicated with a larger cohort.  

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Myocardial strain abnormalities in fetuses with pulmonary atresia and intact ventricular septum.

Cohen J, Binka E, Woldu K, Levasseur S, Glickstein J, Freud LR, Chelliah A, Chiu JS, Shah A. Ultrasound Obstet Gynecol. 2019 Apr;53(4):512-519. doi: 10.1002/uog.19183. Epub 2019 Mar 12. PMID: 30043402   Take Home Points: Myocardial strain is a technique to objectively assess fetal ventricular function compared with standard 2D echocardiography. Fetuses with pulmonary atresia/intact ventricular septum have decreased global longitudinal strain of both the left and right ventricles compared with controls Combining LV and RV global longitudinal strain assessments with other. echocardiographic parameters, listed in Table 3, may allow development of a scoring system to predict presence of RV dependent coronary circulation and may provide valuable prognostic information for prenatal counseling. Comment from Dr. Shelby White (Tucson AZ), section editor of Fetal Cardiology Journal Watch:  Pulmonary atresia with intact ventricular septum (PA/IVS) has a wide range of potential outcomes, based in part on the presence of abnormal communications between the right ventricle and the coronary arteries, most severely the presence of right ventricle-dependent coronary circulation (RVDCC).  Myocardial strain analysis has been used in fetal echocardiography as a sensitive way to identify ventricular dysfunction compared with more subjective measures.  This technique uses speckle-tracking to assess myocardial deformation and is reported as a negative number, with a lower absolute value indicating worse strain/worse ventricular function. This study sought to identify differences in myocardial strain in fetuses with PA/IVS compared with controls and in PA/IVS fetuses with and without RVDCC.   57 fetuses with PA/IVS were analyzed, mean gestational age of 26.3 + 5 weeks.  Left ventricular global longitudinal strain (LV-GLS) was significantly decreased in PA/IVS compared with controls, P < 0.001.  Right ventricular global longitudinal strain (RV-GLS) was also significantly decreased in PA/IVS, P < 0.0001; it was also more difficult to measure as only 42 fetuses had images sufficient for speckle tracking.   Among fetuses with PA/IVS, LV-GLS was decreased in those with RVDCC (Table 3).  The only difference in outcomes that was identified was a decreased RV-GLS in fetuses that had single ventricle palliation compared with biventricular repair.

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Maternal biomarkers for fetal heart failure in fetuses with congenital heart defects or arrhythmias.

Miyoshi T, Hosoda H, Nakai M, Nishimura K, Miyazato M, Kangawa K, Ikeda T, Yoshimatsu J, Minamino N. Am J Obstet Gynecol. 2019 Jan;220(1):104.e1-104.e15. doi: 10.1016/j.ajog.2018.09.024. Epub 2018 Sep 28. PMID: 30273582   Take Home Points: Diagnosis of fetal heart failure is challenging and primarily depends on ultrasound findings such as the cardiovascular profile (CVP), which is routinely used in fetal echocardiography. Maternal serum concentrations of 3 cytokines: TNF-a, VEGF-D, and HBEGF-like GF, were associated with fetal heart failure. How this data may change management is yet unclear, but could potentially impact how we diagnose the severity of heart failure as well as determine the efficacy of fetal therapy. Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Fetal Cardiology Journal Watch:  This interesting study out of Japan looked at a panel of inflammatory serum biomarkers to try to diagnose heart failure in a cohort of infants with congenital heart defects or arrhythmias. The goal was to try to find biomarkers that would cross the placenta and be detected via maternal blood work instead of percutaneous umbilical blood sampling. 50 singletons with either CHD or arrhythmias as diagnosed on fetal echocardiograms and 50 controls were followed. Maternal serum samples were collected and analyzed for 2 hormones and 36 cytokines using the Bio-Plex Pro Human Cancer Biomarker Panels 1 and 2 at 10-14 weeks, 28-33 weeks, and 34-39 weeks. Concurrent, usually biweekly, fetal echocardiograms were obtained to monitor arrhythmia status and CVP (see table 1), with a score of </= 7 defined as heart failure until 37 weeks gestation, when all patients were admitted to the hospital and followed at least weekly until delivery.All controls had a CVP of 10. All other baseline perinatal characteristics were not significantly different between groups. Of 37 fetuses with CHD, 1 had tricuspid valve dysplasia and moderate TR, with a CVP of 7. 8/13 fetuses with an arrhythmia had a tachyarrhythmia (SVT/EAT/atrial flutter) that cardioverted with treatment. No fetus with complete heart block had a change in CVP over the remainder of gestation, regardless of fetal treatment (e.g. dexamethasone). A total of 5 of the arrhythmia patients had a CVP between 5-7 during the 28-33 week period and 3 (all with CHB) at 34-39 weeks. 2/3 had been diagnosed with CHB in the previous period (see Table 2). After testing for cytokine stability in the serum samples of volunteers, the maternal samples were compared between patients with (n=6) and without heart failure (n=61) at 28-33 weeks. The “without heart failure” group included 45 controls, 10 with CHD, and 6 with arrhythmias). Baseline perinatal characteristics and other lab data were similar between groups. A principal component analysis was done to determine which of the hormones and cytokines were most important (see Figure 2). Table 3 shows the 6 variables that showed a statistically significant difference, and table 4 shows the results of univariate and multivariate analysis.  Cut-off values calculated using ROC analysis is shown in Table 5. Including TNF-a + VEGF-D + HB-EGF resulted in a 100% sensitivity and 80% specificity, with an NPV of 100. This study showed that 3 cytokines were associated with heart failure in fetuses. In those without heart failure (by CVP), all maternal serum levels were similar, regardless of the presence of CHD or treated arrhythmias. The authors speculate whether these cytokines are present due to fetal heart failure triggering a maternal inflammatory response to an inflamed placenta (mirror syndrome). Clear limitations to this study include the fact that only a specific set of cytokines/hormones were studied and the most severe cases were excluded as they were treated in many cases (or delivered prematurely).  They also did not include the most common cause of fetal heart failure, placental insufficiency, so this could have a different biomarker pattern. Additionally, it is unclear whether this level of diagnostic testing can be more helpful than following CVP in terms of determining when to treat or deliver, or whether outcomes may be improved, but this was a very interesting first step towards hopefully other larger and more long-term studies in the future.

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Congenital Heart Disease: Prenatal Diagnosis and Genetic Associations.

Hopkins MK, Dugoff L, Kuller JA. Obstet Gynecol Surv. 2019 Aug;74(8):497-503. doi: 10.1097/OGX.0000000000000702. PMID: 31418452 Similar articles Select item 31125476   Take Home Points: If congenital heart disease (CHD) is suspected on prenatal testing, parents should be referred for genetic counselling and/or genetic testing. There are several maternal risk factors for fetal CHD including advanced maternal age, diabetes mellitus, obesity and exposures (ex: alcohol and cocaine). Common genetic conditions associated with a prenatal diagnosis of CHD include chromosomal abnormalities and single-gene defect disorders. Commentary from Dr. Charlotte Van Dorn (Rochester, MN), section editor of Pediatric Cardiology Journal Watch:  Congenital heart disease (CHD) remains the most common birth defect (approximately 4-50 per 1000 live births) and is associated with several genetic syndromes. The early detection of CHD can allow for appropriate perinatal referrals and can improve survival in infants; early detection can also provide information regarding post-natal prognosis. Risk factors for CHD include a family history of CHD, coexisting maternal disease (ex: diabetes mellitus), teratogen exposure (ex: lithium), advanced maternal age, monochorionic twinning, maternal obesity, maternal alcohol and drug use (ex: cocaine) and in vitro fertilization. Fetal echocardiography should be obtained if there is concern for an abnormal cardiac screening ultrasound (US) and/or predisposition to genetic CHD. The detection of other structural abnormalities by prenatal US increases the risk of genetic syndromes associated with CHD. Chromosomal disorders (trisomy 13, 18 and 21) make up 8-10% of CHD. These conditions, especially trisomy 21, can be associated with advanced maternal age. Approximately 50% of infants with trisomy 21 will have CHD, while up to 85% of infants with trisomy 13 and up to 94% of infants with trisomy 18 will have CHD. More common defects include atrial and ventricular septal defects as well as patent ductus arteriosus. One third of patients with trisomy 13 and up to 24% of patients with trisomy 18 will have complex CHD. Turner syndrome, involving complete or partial absence of one X chromosome, has a CHD incidence of 23-50%. This most commonly involves left-sided obstructive lesions such as bicuspid aortic valve (12-18%) and coarctation of the aorta (7-18%). CHD is also common in DiGeorge syndrome (22q11.2 deletion syndrome) occurring in up to 81% of patients. Infants born with conotruncal defects have a 50% likelihood of having DiGeorge Syndrome. Single-gene defect disorders account for 3-5% of CHD and can often be associated with noncardiac malformations. Common single-gene defect disorders include Noonan Syndrome, Alagille Syndrome, and Holt-Oram Syndrome. Perinatal genetic testing options include karyotype, chromosomal microarray (CMA) and amniocentesis. These tests do not detect every genetic disease or syndrome and for single-gene defects, specific gene panels and/or whole exome sequencing may be required. Genetic testing should not be performed without pretest genetic counselling.  

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Outcomes After Extracorporeal Cardiopulmonary Resuscitation of Pediatric In-Hospital Cardiac Arrest: A Report From the Get With the Guidelines-Resuscitation and the Extracorporeal Life Support Organization Registries

Outcomes After Extracorporeal Cardiopulmonary Resuscitation of Pediatric In-Hospital Cardiac Arrest: A Report From the Get With the Guidelines-Resuscitation and the Extracorporeal Life Support Organization Registries. Bembea MM, Ng DK, Rizkalla N, Rycus P, Lasa JJ,...

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Classification scheme for ductal morphology in cyanotic patients with ductal dependent pulmonary blood flow and association with outcomes of patent ductus arteriosus stenting

Classification scheme for ductal morphology in cyanotic patients with ductal dependent pulmonary blood flow and association with outcomes of patent ductus arteriosus stenting. Qureshi AM, Goldstein BH, Glatz AC, Agrawal H, Aggarwal V, Ligon RA, McCracken C, McDonnell...

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