Cell Biochem Biophys
DOI 10.1007/s12013-015-0551-6
ORIGINAL PAPER
Congenital Heart Disease: Causes, Diagnosis, Symptoms,
and Treatments
RongRong Sun • Min Liu • Lei Lu •
Yi Zheng • Peiying Zhang
Ó Springer Science+Business Media New York 2015
Abstract The congenital heart disease includes abnor-
malities in heart structure that occur before birth. Such
defects occur in the fetus while it is developing in the
uterus during pregnancy. About 500,000 adults have con-
genital heart disease in USA (WebMD, Congenital heart
defects medications, www.WebMD.com/heart-disease/tc/
congenital-heart-defects-medications, 2014). 1 in every
100 children has defects in their heart due to genetic or
chromosomal abnormalities, such as Down syndrome. The
excessive alcohol consumption during pregnancy and use
of medications, maternal viral infection, such as Rubella
virus, measles (German), in the first trimester of pregnancy,
all these are risk factors for congenital heart disease in
children, and the risk increases if parent or sibling has a
congenital heart defect. These are heart valves defects,
atrial and ventricular septa defects, stenosis, the heart
muscle abnormalities, and a hole inside wall of the heart
which causes defect in blood circulation, heart failure, and
eventual death. There are no particular symptoms of con-
genital heart disease, but shortness of breath and limited
ability to do exercise, fatigue, abnormal sound of heart as
heart murmur, which is diagnosed by a physician while
listening to the heart beats. The echocardiogram or
RongRong Sun and Min Liu have contributed equally to this work.
R. Sun
M. Liu
L. Lu
Y. Zheng
Graduate School, Nanjing University of Chinese Medicine,
Nanjing 210023, Jiangsu, China
P. Zhang (&)
Department of Cardiology, Xuzhou Central Hospital, Affiliated
Xuzhou Hospital, Medical School of Southeast University,
Xuzhou Clinical Medical College of Nanjing University of
Chinese Medicine, 199# South Jiefang Road,
Xuzhou 221009, Jiangsu, China
e-mail: contribution026@163.com
transesophageal echocardiogram, electrocardiogram, chest
X-ray, cardiac catheterization, and MRI methods are used
to detect congenital heart disease. Several medications are
given depending on the severity of this disease, and cath-
eter method and surgery are required for serious cases to
repair heart valves or heart transplantation as in endocar-
ditis. For genetic study, first DNA is extracted from blood
followed by DNA sequence analysis and any defect in
nucleotide sequence of DNA is determined. For congenital
heart disease, genes in chromosome 1 show some defects in
nucleotide sequence. In this review the causes, diagnosis,
symptoms, and treatments of congenital heart disease are
described.
Keywords Congenital heart disease
Chromosomal
abnormalities
Viral infection
Introduction
Congenital heart disease is the most common congenital
anomaly in newborn babies [1]. Cardiac malformations
have been produced in multiple experimental animal
models, by perturbing selected molecules that function in
the development pathways involved in myocyte specifica-
tion, differentiation, or cardiac morphogenesis [1]. The
precise genetic, epigenetic, environmental basis for various
perturbations in human heart is not fully understood yet.
The past 40 years of genetics research of heart diseases has
indicated some advancement in the understanding of
human genome analyses of rare Mendelian congenital heart
disease families, and by DNA genes sequencing in the
blood of patients of congenital heart disease cohorts.
Although discovery of penetrance of disease gene muta-
tions is known, and such studies have provided three
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notable insights: (1) human congenital heart disease
mutations impact a heterogeneous set of molecules that
orchestrates cardiac development, (2) congenital heart
disease mutations often alter gene-protein dosage, and (3)
identical pathogenic congenital heart disease mutations
cause a variety of distinct malformations, implying that
higher-order interactions account for particular congenital
heart disease phenotypes [1].
Genomic Studies of Congenital Heart Diseases
The genomic technology and single nucleotide polymorphism
array, the next generation sequencing of genes, and copy
number variant platforms are making a rapid discovery to
identify genetic causes of congenital heart disease. Although,
such studies of congenital heart disease are sporadic presented,
the detailed study of the genome from monogenic congenital
heart disease parents and families will explain the genetic
defects and architecture of congenital heart disease. The recent
developments on the molecular genetics of congenital heart
disease have been described by Wolf and Basson [2], as well as
the interactions of genes and pathways during the development
of congenital heart disease are presented. The discovery of
specific genes that cause lesions and some previously identified
genes are mentioned. T-box, NK, and GATA transcription
factors have been associated with a variety of syndromic and
isolated congenital heart defects. The redundant roles of NKx
2.5 and NKx 2.7 along with the interaction of NKx 2.7 with
TBx 20 are elucidated. Other classes of transcription factors are
also being elucidated. The 22q11.2 deletion and microdupli-
cation syndromes and their genetic interactions have been
studied. The recent research also highlights PTPN11 and
NOTCH1 in Noonam syndrome in the genetics of congenital
heart disease. These genetic interactions will further provide a
leading role in the better understanding of downstream tran-
scriptional or signaling pathways of this genetic disease. The
repair of genetic defects in blood or gene therapy may provide
necessary treatment for the congenital heart disease in children,
adolescents, and adults.
The first step for genetic study is to extract DNA from
blood samples by salt precipitation method to study the
sequence of DNA in normal versus diseased blood samples,
and observe the gene defects in the nucleotide sequence of
DNA strand. Such earlier gene studies reported a gene defect
on chromosome 1 for congenital heart disease [7].
Diagnosis of Congenital Heart Disease
The test and diagnosis of congenital heart disease in chil-
dren or adults can be performed by taking blood pressure
and electrocardiogram (ECG) or X-ray of heart patients
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Cell Biochem Biophys
(Tests and diagnosis) [3]. When blood does not flow nor-
mally through vessels, there is a sound of heart murmur in
heart beat which is measured by stethoscope to examine the
heart defects. Following tests are used to diagnose con-
genital heart disease.
Fetal Echocardiogram
An ultrasound waves test is done to create a picture of fetal
heart and this test detects a heart defect before the birth,
thus facilitate for a better treatment plan.
Echocardiogram
A regular echocardiogram is taken to diagnose a congenital
heart defect after a child is born. An ultrasound test pro-
duces images of the heart defect. An echocardiogram also
allows to observe heart beat of child and to identify
abnormalities in the heart muscle and valves.
Electrocardiogram
The ECG test records the electrical activity of the heart and
can help diagnose heart defects or rhythm problems. The
electrodes are connected to a computer. The electrodes are
placed on the chest of the patient which shows waves that
indicate how the heart is beating in a child or an adult.
Chest X-ray
The chest X-ray is important for both, child and adult to see
if the heart is enlarged, or if the lungs have extra blood or
other fluid in them which can produce a heart failure.
Pulse Oximetry
This test measures how much oxygen is in the blood. A
sensor is placed at the end of a finger to record the amount
of oxygen in blood. Low oxygen in the blood indicates that
child has a heart problem.
Cardiac Catheterization
In this test, a thin flexible tube (catheter) is inserted into a
blood vessel at groin and guided through into the heart. The
catheterization is sometimes necessary because it provides
a detailed view of heart defects than an echocardiogram.
Symptoms of Congenital Heart Disease
Congenital heart disease can have a range of symptoms due
to conditions of different types of heart defects [4]. The
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general signs of this disease include: excessive sweating,
extreme tiredness, fatigue, poor feeding, rapid heartbeat,
shortness of breath, chest pain, blue tinge to the skin
(cyanosis), and clubbed fingernails. The congenital heart
disease develops shortly after birth and the symptoms do
not develop until early childhood or teenage years. How-
ever, some complications may develop during adulthood
such as problem with growth and development of heart and
body, the infections of respiratory tract, throat, lungs and
sinuses, heart infection, endocarditis, pulmonary hyper-
tension, high blood pressure, and the heart being unable to
pump enough blood which can cause a heart failure.
Treatment of Congenital Heart Disease
Heart surgeons repair congenital heart defects using cath-
eter or surgical methods (NIH, National Heart, Lung and
Blood Institute, US.) [5]. Many medications are known for
the treatment of congenital heart disease. However, the use
of catheter procedure is easier than surgery. A catheter
(thin, flexible tube) is inserted into a vein or an artery, after
the skin is punctured by a thin needle. In this case the open-
heart surgery can be avoided to repair the heart defect, but
in severe cases of a hole in the inner wall of the heart, the
stitches or a patch is needed to repair the inner wall and
valves of heart.
Catheter Method
The catheter method has been used successfully since the
past 20 years by many heart surgeons to repair heart
defects, such as atrial septal defect (ASD) and pulmonary
valve stenosis. For ASD repair, a catheter is inserted into a
vein in the groin (upper thigh) of patient and threads the
tube to the heart’s septum. An umbrella-like device is
attached to the catheter. When the catheter reaches the
septum, the device is pushed out of the catheter. The device
is placed so that it plugs the hole between the atria, secured
in place, and catheter is withdrawn from the body. Within
6 months the normal tissue grows in and on the device, and
the closure device does not need to be replaced as the child
grows.
In pulmonary valve stenosis, a catheter is inserted into a
vein and is threaded to the pulmonary valve of the heart. A
tiny balloon at the end of the catheter is quickly inflated to
push apart the leaflets, or doors of the valve. The balloon is
then deflated and the catheter and balloon are withdrawn.
This method is used to repair any narrow valve in the heart.
The catheter is guided by the use of echocardiography and
transesophageal echocardiogram (TEE), and coronary
angiography. The heart pictures are taken through the
esophagus, a passage leading from mouth to stomach. The
TEE examines complex defects in the heart.
Surgery Method
An open-heart surgery is performed in patients if heart
defect is serious and cannot be repaired by catheter
method. Usually one or more heart surgeries are required
depending upon the severity of the congenital heart disease.
The heart surgeons may use open-heart surgery to: close
holes in the heart with stitches or a patch, repair or replace
heart valves, widen arteries or openings to heart valves,
repair complex defects, such as problems with the location
of blood vessels near the heart or how they are formed.
Rarely, babies are born with multiple defects that are too
complex to repair and these babies need another new heart
after their birth. In these cases, heart transplant surgery
using a healthy heart of a child of same age and blood type
is performed.
Types of Medications used for Congenital Heart Disease
Many medications for the treatment of congenital heart
defects are available as described by The Heart Disease
Health Center ([6]). These medicines are necessary for
patients to correct the defect in the heart and help to repair
it. Certain medications may have to be taken for a long
time to keep the heart beating properly and for the appro-
priate blood circulation in the body. For many heart defects
and diseases, the use of diuretics, digoxin, vasodilators, and
antiarrhythmic drugs have been recommended. The heart
defects can also be treated by prostaglandins and prosta-
glandin inhibitors to keep the fetal blood vessel opened,
and is called as ductus arteriosus, that normally closes at
birth. Antibiotics are used for endocarditis before surgery.
Aspirin is used as a blood thinner or anticoagulant which
lowers the risk of blood clots in the heart or blood vessels.
However, many heart defects can be a part of genetic
and chromosomal syndromes. Some of these syndromes
may be passed down through parents and families. The
examples are: DiGeorge syndrome, Down syndrome,
Marfan syndrome, Noonan syndrome, Trisomy 13, and
Turner syndrome. For congenital heart disease, the genetic
study of defective genes or DNA sequence is important to
observe to identify which gene has abnormal nucleotide
sequence. Gene therapy using new, modern genetic meth-
ods of RNA and DNA technologies can repair such
defective genes in DNA sequences. Moreover, genomic
study is time consuming and will take 100 years or more to
understand correct human genome. Certain genes are
defective from childhood so how to repair their DNA
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sequences or to repair and correct their genetic materials by
gene therapy is a challenging research for future [1].
However, various types of congenital heart defects or dis-
eases have been described by [4], such as, aortic valve
stenosis, coarctation of the aorta, Ebstein’s anomaly, patent
ductus arteriosus, pulmonary valve stenosis, septal defects
(including atrial septal defects and ventricular septal
defects), single ventricle defects (including tricuspid atre-
sia, and hypoplastic left heart syndrome), Tetralogy of
Fallot, total anomalous pulmonary venous connection,
transposition of the great arteries, and truncus arteriosus.
There is a need for the genetic research of blood DNA
sequences to further study congenital heart defects in
children after birth, in adolescents, and adult patients.
Conclusion
Congenital heart disease is the most common congenital
anomaly in newborn babies and adolescents. The heart
genetics research since past 40 years has shown some
advancement in the understanding of human genome
analyses of rare Mendelian congenital heart disease by
gene sequencing, and blood DNA analyses of heart disease
cohorts [1].
About 500,000 persons have congenital heart disease in
USA [6]. 1 in 100 children and young teenagers have
defects in their heart’s inner-walls or valves which is due to
genetic or chromosomal abnormalities, such as Down
syndrome. The catheter and surgery procedures can repair
the heart defects in congenital heart disease. The diagnosis
of this disease can be done by ECG and X-ray and other
methods. Some medications are useful to protect the heart
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Cell Biochem Biophys
from further defects or damages and heart failure in chil-
dren, teenagers, or adults. The future studies of blood DNA
sequences and human genome are necessary to understand
the genetic defects and how to repair these by gene therapy.
The discovery of new medications is also important for this
heart disease.
References
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