Fetal Cardiology Featured Articles of November 2016

Cardiac output and blood flow redistribution in the fetus with D-loop transposition of the great arteries and intact ventricular septum: insights into the pathophysiology.

Godfrey ME, Friedman KG, Drogosz M, Rudolph AM, Tworetzky W.

Ultrasound Obstet Gynecol. 2016 Nov 22. doi: 10.1002/uog.17370. [Epub ahead of print]

Take Home Points:

  1. In normal fetal circulation the right ventricle contributes about 60% to combined cardiac output. In d-transposition of the great arteries (d-TGA) with intact ventricular septum the right and left ventricular components of combined ventricular output are about equal.
  2. 75% of fetuses with d-TGA with intact ventricular septum had bidirectional flow across the foramen ovale and about a third had bidirectional flow at the ductus arteriosus.
  3. These findings support previous postulations from Dr. Rudolph concerning the pathophysiology of fetal blood flow in d-TGA. Specifically, that increased pulmonary arterial p02 leads to pulmonary vasodilation that in turn increases pulmonary artery blood flow with subsequent increases in pulmonary venous return to the left atrium raising the left atrial pressure contributing to bidirectional flow across the foramen ovale.

Abarbanell picture smallCommentary from Dr. Ginnie Abarbanell (Atlanta), section editor of Fetal Cardiology Journal Watch: This fetal study evaluated the changes in blood flow physiology in d-transposition of the great arteries (d-TGA) with intact ventricular septum compared to normal fetal cardiac blood flow.  Data was collected on 74 consecutive fetuses with d-TGA with intact ventricular septum.  Compared to the controls the left ventricular component of combined ventricular output was higher at 50.7% compared to 40.2% with no difference in total combined ventricular output.  75.7% of fetuses had bidirectional flow at the foramen ovale and slightly over a third (32.4%) had bidirectional flow at the ductus arteriosus.  Bidirectional shunting was more common in the 3rd trimester.  The pulmonary valve is larger compared to the aortic valve in normal fetuses.  In this study, the pulmonary and aortic valves were nearly identical in size.  There was no difference in the middle cerebral artery Doppler indices or pulsatility index found in fetuses with d-TGA vs. normal fetuses.  In the discussion, the authors relate these findings to those postulated by Dr. Rudolph 1 who proposed that increased pulmonary arterial p02 as in d-TGA leads to pulmonary vasodilation and constriction of the ductus arteriosus in turn increasing the pulmonary artery blood flow.  The increased pulmonary artery blood flow combined with decreased right to left ductal flow leads to increased pulmonary venous return to the left atrium, which raises the left atrial pressure and contributes to the bidirectional flow across the foramen ovale.  The results from this study are in congruence with Dr. Rudolph’s proposal in that there was increased left ventricular output (i.e. increased pulmonary blood flow) with increased bidirectional shunting at the ductus arteriosus secondary to probable decreased pulmonary resistance and increased bidirectional shunting at the foramen ovale most likely secondary to decreased pulmonary resistance with increased pulmonary venous return to the left atrium.

1. Rudolph AM. Aortopulmonary transposition in the fetus: speculation on pathophysiology and therapy. Pediatr Res. 2007 Mar;61(3):375–80.

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Toward Improving the Fetal Diagnosis of Coarctation of the Aorta.

Beattie M, Peyvandi S, Ganesan S, Moon-Grady A.

Pediatr Cardiol. 2016 Nov 25. [Epub ahead of print]

Take Home Points:

  1. This study sought to determine the best markers on fetal echocardiogram that predict neonatal coarctation of the aorta.
  2. 2D parameters of ascending aorta z-score, aortic isthmus z-score and the aortic isthmus/ductus arteriosus ratio on fetal echo were the most predictive of postnatal coarctation of the aorta.
  3. This study found increased sensitivity for detecting coarctation on fetal echocardiogram when a combination of an aorta/pulmonary ratio ≤ 0.65 and diastolic persistence of flow at the aortic isthmus were present but at the expense of an increased false positive rate.
  4. The authors propose a stepwise evaluation for fetal coarctation with first evaluating the 2D findings (i.e. ascending aorta z-score, aortic isthmus z-score and the aortic isthmus/ductus arteriosus ratio) and if 2D findings are equivocal, then a combination of an aorta/pulmonary artery ratio ≤ 0.65 and diastolic persistence of flow may be useful to further predict the presence of fetal coarctation of the aorta.

Comment from Dr. Ginnie Abarbanell (Atlanta), section editor of Fetal Cardiology Journal Watch: Coarctation of the aorta can be difficult to diagnose in utero and unfortunately has a low detection rate on neonatal pulse oximetry screening.  Hence, several studies have been published trying to identify the most helpful findings on fetal echocardiogram to make a prenatal diagnosis of coarctation.  This retrospective study from the University of California San Francisco reviewed fetal echocardiograms of 62 fetuses with a diagnosis of probable coarctation of the aorta.  72.5% postnatally were confirmed as having a coarctation of the aorta.  The following 2D parameters were the most predictive of postnatal coarctation of the aorta:  ascending aorta z-score, aortic isthmus z-score and the aortic isthmus/ductus arteriosus ratio.  The left ventricle/right ventricular size ratio, presence of an aortic isthmus shelf or the mitral valve/tricuspid valve ratio were not significantly predictors of coarctation.  There was improved sensitivity for presence of postnatal coarctation when there was an aorta/pulmonary artery ratio ≤ 0.65 and diastolic persistence of flow at the aortic isthmus. See Figure.   However, with improved sensitivity there was an increased false positive rate.  The authors propose a “stepwise” approach when diagnosing fetal coarctation.  This approach would initially focus on 2D evaluation of the fetal arch with specific attention to the ascending aorta size (z-score), aortic isthmus size (z-score) and the aortic isthmus/ductus arteriosus ratio.  When these parameters are equivocal, a combination of the aorta/pulmonary artery ratio ≤ 0.65 with diastolic persistence of flow maybe useful to further predict the presence of fetal coarctation of the aorta.

 

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Fetal Cardiology and Genetics Articles – November 2016

  1. Cardiovascular profile score as a predictor of acute intrapartum non-reassuring fetal status in infants with congenital heart defects.

Miyoshi T, Katsuragi S, Neki R, Kurosaki KI, Shiraishi I, Nakai M, Nishimura K, Yoshimatsu J, Ikeda T.

J Matern Fetal Neonatal Med. 2016 Nov 28:1-23. [Epub ahead of print]

  1. ISUOG consensus statement on current understanding of the association of neurodevelopmental delay and congenital heart disease: impact on prenatal counseling.

Paladini D, Alfirevic Z, Carvalho JS, Khalil A, Malinger G, Martinez JM, Rychik J, Ville Y, Gardiner H; ISUOG Clinical Standards Committee.

Ultrasound Obstet Gynecol. 2016 Nov 27. doi: 10.1002/uog.17324. [Epub ahead of print] No abstract available.

  1. Alcohol Exposure Causes Overexpression of Heart Development-Related Genes by Affecting the Histone H3 Acetylation via BMP Signaling Pathway in Cardiomyoblast Cells.

Shi J, Zhao W, Pan B, Zheng M, Si L, Zhu J, Liu L, Tian J.

Alcohol Clin Exp Res. 2016 Nov 24. doi: 10.1111/acer.13273. [Epub ahead of print]

  1. Reference Ranges of Fetal Cardiac Biometric Parameters Using Three-Dimensional Ultrasound with Spatiotemporal Image Correlation M Mode and Their Applicability in Congenital Heart Diseases.

Tedesco GD, de Souza Bezerra M, Barros FS, Martins WP, Nardozza LM, Carrilho MC, Moron AF, Carvalho FH, Rolo LC, Araujo Júnior E.

Pediatr Cardiol. 2016 Nov 23. [Epub ahead of print]

  1. Cardiac output and blood flow redistribution in the fetus with D-loop transposition of the great arteries and intact ventricular septum: insights into the pathophysiology.

Godfrey ME, Friedman KG, Drogosz M, Rudolph AM, Tworetzky W.

Ultrasound Obstet Gynecol. 2016 Nov 22. doi: 10.1002/uog.17370. [Epub ahead of print]

  1. Transcriptomic Profiling Maps Anatomically Patterned Subpopulations among Single Embryonic Cardiac Cells.

Li G, Xu A, Sim S, Priest JR, Tian X, Khan T, Quertermous T, Zhou B, Tsao PS, Quake SR, Wu SM.

Dev Cell. 2016 Nov 21;39(4):491-507. doi: 10.1016/j.devcel.2016.10.014.

  1. Single-Cell Resolution of Temporal Gene Expression during Heart Development.

DeLaughter DM, Bick AG, Wakimoto H, McKean D, Gorham JM, Kathiriya IS, Hinson JT, Homsy J, Gray J, Pu W, Bruneau BG, Seidman JG, Seidman CE.

Dev Cell. 2016 Nov 21;39(4):480-490. doi: 10.1016/j.devcel.2016.10.001.

  1. Genetic determinants of myocardial dysfunction.

Li X, Zhang P.

J Med Genet. 2016 Nov 21. pii: jmedgenet-2016-104308. doi: 10.1136/jmedgenet-2016-104308. [Epub ahead of print] Review.

  1. Automated annotation and quantitative description of ultrasound videos of the fetal heart.

Bridge CP, Ioannou C, Noble JA.

Med Image Anal. 2016 Nov 19;36:147-161. doi: 10.1016/j.media.2016.11.006. [Epub ahead of print]

  1. Successful Fetal Tele-Echo at a Small Regional Hospital.

Brown J, Holland B.

Telemed J E Health. 2016 Nov 18. [Epub ahead of print]

  1. Molecular genetics testing for familial absence of the left ventricular outflow tract: A rare malformation.

Sun F, Chen Y, Xu S, Xiao Y, Ren W, Zhang Y.

Int J Cardiol. 2016 Nov 15;223:7-9. doi: 10.1016/j.ijcard.2016.08.153. No abstract available.

  1. Transgenerational cardiology: One way to a baby’s heart is through the mother.

Jay PY, Akhirome E, Magnan RA, Zhang MR, Kang L, Qin Y, Ugwu N, Regmi SD, Nogee JM, Cheverud JM.

Mol Cell Endocrinol. 2016 Nov 5;435:94-102. doi: 10.1016/j.mce.2016.08.029.

  1. Identification of candidate genes for congenital heart defects on proximal chromosome 8p.

Li T, Liu C, Xu Y, Guo Q, Chen S, Sun K, Xu R.

Sci Rep. 2016 Nov 3;6:36133. doi: 10.1038/srep36133.

  1. In vivo functional consequences of human THRA variants expressed in the zebrafish.

Marelli F, Carra S, Rurale G, Cotelli F, Persani L.

Thyroid. 2016 Nov 3. [Epub ahead of print]

  1. Genetics of Congenital Heart Disease: Past and Present.

Muntean I, Togănel R, Benedek T.

Biochem Genet. 2016 Nov 2. [Epub ahead of print] Review.

  1. 14-3-3epsilon controls multiple developmental processes in the mouse heart.

Gittenberger-de Groot AC, Hoppenbrouwers T, Miquerol L, Kosaka Y, Poelmann RE, Wisse LJ, Yost HJ, Jongbloed MR, Deruiter MC, Brunelli L.

Dev Dyn. 2016 Nov;245(11):1107-1123. doi: 10.1002/dvdy.24440.

  1. Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene.

Jiang Y, Wang D, Zhang G, Wang G, Tong J, Chen T.

Environ Toxicol. 2016 Nov;31(11):1372-1380. doi: 10.1002/tox.22142.

  1. Interchromosomal core duplicons drive both evolutionary instability and disease susceptibility of the Chromosome 8p23.1 region.

Mohajeri K, Cantsilieris S, Huddleston J, Nelson BJ, Coe BP, Campbell CD, Baker C, Harshman L, Munson KM, Kronenberg ZN, Kremitzki M, Raja A, Catacchio CR, Graves TA, Wilson RK, Ventura M, Eichler EE.

Genome Res. 2016 Nov;26(11):1453-1467.

  1. Zebrafish models of cardiovascular disease.

Bournele D, Beis D.

Heart Fail Rev. 2016 Nov;21(6):803-813.

  1. Pre- and Postnatal Diagnosis of 5q35.1 and 8p23.1 Deletion in Congenital Heart Disease.

Shetty M, Srikanth A, Kulshreshtha P, Kadandale J, Hegde S.

Indian J Pediatr. 2016 Nov;83(12-13):1484-1485. No abstract available.

  1. A systematic review of prenatal screening for congenital heart disease by fetal electrocardiography.

Verdurmen KM, Eijsvoogel NB, Lempersz C, Vullings R, Schroer C, van Laar JO, Oei SG.

Int J Gynaecol Obstet. 2016 Nov;135(2):129-134. doi: 10.1016/j.ijgo.2016.05.010. Review.

  1. Surgical repair of left ventricular pseudoaneurysm following perventricular device closure of muscular ventricular septal defect.

Taqatqa AS, Caputo M, Kenny DP, Diab KA.

J Card Surg. 2016 Nov;31(11):697-699. doi: 10.1111/jocs.12840.

  1. Reduced fetal brain fissures depth in fetuses with congenital heart diseases.

Peng Q, Zhou Q, Zang M, Zhou J, Xu R, Wang T, Zeng S.

Prenat Diagn. 2016 Nov;36(11):1047-1053. doi: 10.1002/pd.4931.

  1. Emerging Field of Cardiomics: High-Throughput Investigations into Transcriptional Regulation of Cardiovascular Development and Disease.

Slagle CE, Conlon FL.

Trends Genet. 2016 Nov;32(11):707-716. doi: 10.1016/j.tig.2016.09.002. Review.

  1. Fetal Magnetocardiography using Optically Pumped Magnetometers: A More Adaptable and Less Expensive Alternative?

Eswaran H, Escalona-Vargas D, Bolin EH, Wilson JD, Lowery CL.

Prenat Diagn. 2016 Nov 27. doi: 10.1002/pd.4976. [Epub ahead of print] No abstract available.

  1. Toward Improving the Fetal Diagnosis of Coarctation of the Aorta.

Beattie M, Peyvandi S, Ganesan S, Moon-Grady A.

Pediatr Cardiol. 2016 Nov 25. [Epub ahead of print]

  1. Reference Ranges of Fetal Cardiac Biometric Parameters Using Three-Dimensional Ultrasound with Spatiotemporal Image Correlation M Mode and Their Applicability in Congenital Heart Diseases.

Tedesco GD, de Souza Bezerra M, Barros FS, Martins WP, Nardozza LM, Carrilho MC, Moron AF, Carvalho FH, Rolo LC, Araujo Júnior E.

Pediatr Cardiol. 2016 Nov 23. [Epub ahead of print]

  1. Thorax-to-head ratio and defect diameter-to-head ratio in giant omphaloceles as predictor for fetal outcome.

Diemon N, Funke K, Möllers M, Hammer K, Steinhard J, Sauerland C, Müller V, Klockenbusch W, Schmitz R.

Arch Gynecol Obstet. 2016 Nov 11. [Epub ahead of print]

  1. Prediction of neonatal outcome of TTTS by fetal heart and Doppler ultrasound parameters before and after laser treatment.

Delabaere A, Leduc F, Reboul Q, Fuchs F, Wavrant S, Fouron JC, Audibert F.

Prenat Diagn. 2016 Nov 3. doi: 10.1002/pd.4956. [Epub ahead of print]

  1. Pregnancy complications in singleton pregnancies with isolated fetal heart defects.

van Velzen CL, Türkeri F, Pajkrt E, Clur SA, Rijlaarsdam ME, Bax CJ, Hruda J, de Groot CJ, Blom NA, Haak MC.

Acta Obstet Gynecol Scand. 2016 Nov;95(11):1273-1280. doi: 10.1111/aogs.12955.

  1. Predicting outcome in 259 fetuses with agenesis of ductus venosus – a multicenter experience and systematic review of the literature (.).

Moaddab A, Tonni G, Grisolia G, Bonasoni MP, Araujo Júnior E, Rolo LC, Prefumo F, de la Fuente S, Sepulveda W, Ayres N, Ruano R.

J Matern Fetal Neonatal Med. 2016 Nov;29(22):3606-14. doi: 10.3109/14767058.2016.1144743.

  1. Prenatal Sonographic Predictors of Neonatal Coarctation of the Aorta.

Anuwutnavin S, Satou G, Chang RK, DeVore GR, Abuel A, Sklansky M.

J Ultrasound Med. 2016 Nov;35(11):2353-2364.

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