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ARRA Investments in Pediatric Heart Disease

Public Health Burden
Congenital heart disease is the most common birth defect, affecting about 40,000 newborns every year, and despite numerous advances over the past 30 years it remains the most lethal birth defect in the first year of life.  One-third of affected children have complex malformations requiring multiple surgical and other procedures and imposing considerable financial expense and family disruption.  That more adults than children are now living with congenital heart disease is a testament to the gains in medical and surgical care, but many of those adults have mild or moderate disabilities related to their cardiac conditions.  Their early mortality and ongoing medical issues entail significant societal costs.

The heart is the earliest organ to form in humans, going from a few cells to a complex four-chambered structure beating about 150 times a minute by the 10th week of pregnancy.  Its development requires the execution of countless carefully regulated and precisely timed steps, so it is easy to imagine how a tiny mistake along the way could lead to an abnormal heart.  All of the details about how normal or abnormal hearts are formed are not yet known, but a number of ARRA-funded grants are exploring this fundamental process, including those described below.
  • Many heart defects are caused by gene mutations, which are easy to study in animal models but hard to study in humans during organ development.  An investigator will use state-of-the-art techniques to overcome this barrier and examine the genetic contribution to certain types of heart defects.1
  • Another investigator will examine chromosomal abnormalities that cause certain types of heart defects; this work may lead to individualized preventive interventions for affected children.2
  • Development of the coronary arteries, which supply the needs of the heart muscle itself, is poorly understood but has implications for both adults and children with congenital heart disease.  Researchers will investigate coronary artery development in animal models, with the goal of formulating better strategies for treating coronary artery abnormalities and disease.3
  • When viewed from the outside, the left and right halves of the body are symmetrical, but this is not true for many internal organs, including the fully-formed heart.  Early in development, however, the heart is a symmetric tube.  An investigator is working to understand the development of left-right cardiac asymmetry, which could help provide insights not only into heart development but also into the development of other asymmetrical organs.4
  • Some of the factors that control heart development are also active after birth and affect heart function.  One project seeks to improve understanding of the heart-development process, which could help identify ways to repair damaged heart muscle in adults following a heart attack.5
Very little is available in the way of evidence-based treatment for congenital heart disease or other heart conditions that affect children.  Most treatments are “hand-me-downs” from adult medicine, but children are not just little adults—they respond differently to medicines and need specially tailored surgical therapies.  A number of ARRA funded grants are exploring potential new treatments, a few of which are described below.
  • Children can develop heart failure, but it differs from heart failure in adults.  Drugs that work for adults have not shown much promise in children.  One ARRA investigator is looking at differences in how children and adults respond to one type of drug in order to improve treatment.6
  • Studies of treatments for rare diseases such as congenital heart disease are problematic because of the relatively limited number of study subjects and concerns about the safety of potential interventions.  An investigator will link existing data sets to look at how variations in managing children during open-heart surgery can affect outcome.  This work will provide preliminary information that can be used to plan future clinical studies.7
  • Undergoing heart surgery and recovering from it pose particular risks for children.  A project is determining the effects of various aspects of postoperative management in intensive care units on recovery.8
  • After birth, blood flow follows a somewhat different pattern than before birth because of lung expansion and removal of the placenta.  A key component of the change is closure of a blood vessel called the ductus arteriosus.  In some newborns with congenital heart disease, keeping the ductus arteriosus open is the only way to keep a child alive until corrective surgery can be performed.  One researcher is investigating the factors that regulate the closure of the ductus after birth.9
  • Though not a congenital heart disease, progeria causes death in childhood due to extremely rapid aging and accelerated heart disease.  One investigative team is testing a new 3-drug combination in this extremely rare and uniformly lethal condition.10
  • Attention Deficit Hyperactivity Disorder (ADHD) is particularly common in children with congenital heart disease, and some of them may be at risk of sudden cardiac death when they take medicines for ADHD. One investigator is using mathematical models to compare various cardiac screening strategies prior to starting medicines for ADHD. This is a very practical approach, because sudden cardiac death is rare, and the modeling can be used to identify screening strategies most likely to be effective before testing them in children.11

  1. 1RC1HL099618-01 -- Characterization of cardiac progenitors derived from 22q11-deleted patients -- Pu, William T (MA)
  2. 1R01HL092330-01A1 -- Chromosomal microdeletions causing heart defects -- Lammer, Edward J (CA)
  3. 1R01HL091171-01A1 -- Regulation of coronary vascular development by differential tissue hypoxia -- Watanabe, Michiko (OH)
  4. 1R01HL095690-01 -- Regulation of ciliated cells that control cardiac laterality -- Amack, Jeffrey D (NY)
  5. 3R01HL081577-05S1 -- Nkx2.5-dependent pathways in postnatal cardiomyocytes -- Kasahara, Hideko (FL)
  6. 1R21HL097123-01 -- Cardiac beta-adrenergic adaptation in pediatric heart failure -- Stauffer, Brian L (CO)
  7. 1RC1HL099941-01 -- Comparative effectiveness of medications used in congenital heart surgery -- Li, Jennifer S (NC)
  8. 3R01HL088448-02S1 -- SPECS: Safe pediatric euglycemia in cardiac surgery -- Agus, Michael (MA)
  9. 3R01HL077395-04S1 -- Mechanisms of ductus arteriosus regulation -- Reese, John Jeffrey (TN)
  10. 1RC2HL101631-01 -- Phase II trial of lonafarnib, pravastatin and zoledronic acid in progeria -- Kieran, Mark W (MA)
  11. 1RC1HL100546-01 -- Comparative effectiveness of ECG screening in children with ADHD -- Leslie, Laurel K (MA)

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Page Last Updated on June 30, 2018 NIH...Turning Discovery Into Health®