Fetal Cardiology Featured Articles of June 2015

1. Flow patterns in the ductus arteriosus during open fetal myelomeningocele repair.

Howley L, Wood C, Patel SS, Zaretsky MV, Crombleholme T, Cuneo B.

Prenat Diagn. 2015 Jun;35(6):564-70. doi: 10.1002/pd.4573. Epub 2015 Mar 18.

PMID: 25663164

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Abarbanell picture smallComment from Dr. Ginnie Abarbanell (Atlanta), section editor of Fetal Cardiology Journal Watch:  This is the first reported longitudinal evaluation of flow patterns in the ductus arteriosus before, during, and after fetal myelomeningocele (MMC) repair.  Women who undergo fetal myelomeningocele repair are given tocolytic agents such as indomethacin, magnesium, and nifedipine before and after fetal MMC repair to prevent premature labor. Indomethacin is well known to cause fetal ductal constriction.  Additionally, fetuses undergoing MMC repair are also exposed high-oxygen concentrations, known to cause constriction of the ductus arteriosus, and general inhalational agents such as desflurane, which can cause negative inotropic effects on the fetal heart.  This longitudinal evaluation identified 3 distinct ductal flow patterns indicating varying degrees of ductal constriction.  See figure.  “All ten fetuses exhibited type I flow pattern after receiving indomethacin preoperatively”. 6 fetuses progressed to type II flow and 2 fetuses to type III flow.  Type III flow is  consistent with severe ductal constriction and ventricular dysfunction. The most severe ductal constriction seemed to occur during the time of inhaled anesthesia.  Ductal constriction seemed to improve by the second postoperative day (see figure).

Take home points:

  1. Ductal constriction does occur with fetal surgery and maybe secondary to many factors including the use of indomethacin as a tocolytic, high oxygen exposure and general anesthetic agents.
  2. The most severe ductal constriction occurred when the mother received inhaled anesthesia.
  3. One could speculate that similar findings also occur in other situations besides with fetal surgery for example when mothers receive indomethacin for tocolysis or general anesthetics for other surgeries during pregnancy.

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2. Why increased nuchal translucency is associated with congenital heart disease: a systematic review on genetic mechanisms.

Burger NB, Bekker MN, de Groot CJ, Christoffels VM, Haak MC.

Prenat Diagn. 2015 Jun;35(6):517-28. doi: 10.1002/pd.4586. Epub 2015 May 19.

PMID: 25728762

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Comment from Dr. Ginnie Abarbanell (Atlanta), section editor of Fetal Cardiology Journal Watch:  This is an interesting systematic review of the literature regarding genes involved in cardiac and lymphatic development in mouse embryos.  The authors hypothesize that there is a link between the genes involved in cardiac and lymphatic vascular development given the high incidence of congenital heart defects in fetuses with  increased nuchal translucency (nuchal edema).  Furthermore, both nuchal edema and congenital heart defects have been linked to abnormal endothelial differentiation in the fetus.  A systematic search of the Mammalian Phenotype Browser (Mouse Genome Informatics), MEDLINE and EMBASE was performed.  Fifteen candidate genes involved in both cardiac and lymphatic development were identified from the literature search.   These identified genes may further unlock our understanding of cardiac genetics.

Take home points:

  1. As the authors conclude: “The mutual candidate genes obtained in this systematic review will provide an opportunity to be studied morphologically in various mouse models and human fetuses for their clinical relevance. We hypothesize that the 15 identified mutual genes are the first step in exploring underlying genetic mechanisms in the pathophysiology of increased nuchal translucency”
  2. These genes may further unlock our understanding of cardiac genetics

3. Timing of diagnosis affects mortality in critical congenital heart disease.

Eckersley L, Sadler L, Parry E, Finucane K, Gentles TL.

Arch Dis Child. 2015 Jun 30. pii: archdischild-2014-307691. doi: 10.1136/archdischild-2014-307691. [Epub ahead of print]

PMID: 26130379

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Shaji Menon Portrait 12.15.14Comment from Dr. Shaji Menon (Salt Lake City, UT), section editor of Pediatric Cardiology Journal Watch: Late diagnosis of congenital heart diseases (CHD) may be associated with increased mortality and morbidity. The goal of prenatal ultrasound screening  and postnatal pulse oximetry screening for critical congenital heart disease (CCHD) is to improve early detection and prevent mortality and morbidity associated with delayed diagnosis of CCHD. The objective of this retrospective population based study from New Zealand was to evaluate proportion and outcome of major CHD diagnosed before (early) or after (late) postnatal discharge. The investigators found that late diagnosis of heart defect occurred in 20% of critical and 51% of non-critical cases. In CCHD, the mortality was 18% compared to 8% in non-critical CHD. Mortality was lower in cohort with early diagnosis of critical CHD compared to the late diagnosis cohort (16% vs 27%, p=0.04). Following early diagnosis, the mortality benefit was highest in Isolated critical CHD (12% vs 29%, p=0.002). Early diagnosis occurred in >90% critical complex CHD and hypoplastic left heart syndrome, 85% d-transposition of the great arteries (d-TGA) and 53% critical left ventricular outflow tract obstruction (LVOTO). Deaths in d-TGA and LVOTO mostly occurred prior to intervention. In d- TGA, mortality was associated with birth distant from the cardiac centers.

Key findings of clinical importance:

  1. Late diagnosis of critical CHD is associated with higher mortality
  2. Death associated with delayed diagnosis of critical LVOTO (e.g. coarctation) may not be completely prevented by pulse oximetry screen due to low pickup rates of LVOTO on pulse oximetry screen.
  3. Higher mortality associated with delayed diagnosis and delivery distant from cardiac centers in D-TGA patients indicate the need for improving measures to improve prenatal detection of D-TGA and delivery of these patients in tertiary care cardiac centers for early intervention if needed.

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