WEEK 1

1. Respiratory distress syndrome

Respiratory distress syndrome, also known as hyaline membrane disease, occurs almost
exclusively in premature infants. The incidence and severity of respiratory distress syndrome are
related inversely to the gestational age of the newborn infant. (See Etiology and Epidemiology.)
Enormous strides have been made in understanding the pathophysiology and management of
respiratory distress syndrome, leading to improvements in morbidity and mortality in infants with
the condition. Advances include the following (see Treatment and Medication):
 The use of antenatal steroids to enhance pulmonary maturity
 Appropriate resuscitation facilitated by placental transfusion and immediate use of continuous
positive airway pressure (CPAP) for alveolar recruitment
 Early administration of surfactant
 The use of gentler modes of ventilation, including early use of "bubble" nasal CPAP to
minimize damage to the immature lungs
 Supportive therapies, such as the diagnosis and management of patent ductus arteriosus
(PDA), fluid and electrolyte management, trophic feeding and nutrition, and the use of
prophylactic fluconazole
These therapies have also resulted in the survival of extremely premature infants, some of who
continue to be ill with complications of prematurity. (See the image below.)

Chest radiographs in a premature infant with respiratory distress syndrome before and after
surfactant treatment. Left: Initial radiograph shows poor lung expansion, air bronchogram, and
reticular granular appearance. Right: Repeat chest radiograph obtained when the neonate is aged
3 hours and after surfactant therapy demonstrates marked improvement.
View Media Gallery
Complications
Although reduced, the incidence and severity of complications of respiratory distress syndrome
can result in clinically significant morbidities. Sequelae of respiratory distress syndrome include
the following (see Prognosis, Clinical, and Workup):
 Septicemia
 Bronchopulmonary dysplasia (BPD)
 Patent ductus arteriosus (PDA)
 Pulmonary hemorrhage
 Apnea/bradycardia
 Necrotizing enterocolitis (NEC)
 Retinopathy of prematurity (ROP)
 Hypertension
 Failure to thrive
 Intraventricular hemorrhage (IVH)
 Periventricular leukomalacia (PVL) - With associated neurodevelopmental and audiovisual
handicaps
Strategic goals include focusing direct attention on anticipating and minimizing these
complications and preventing premature delivery whenever possible. (See the diagram below.)
Schematic outlines the pathology of respiratory distress syndrome (RDS). Infants may recover
completely or develop chronic lung damage, resulting in bronchopulmonary dysplasia (BPD). FiO2
= fraction of inspired oxygen; HMD = hyaline membrane disease; V/Q = ventilation perfusion.
Surfactant formation and physiology
Surfactant is a complex lipoprotein (see the image below) composed of 6 phospholipids and 4
apoproteins. Surfactant recovered by alveolar wash from most mammals contains 70-80%
phospholipids, 8-10% protein, and 10% neutral lipids, primarily cholesterol. Dipalmitoyl
phosphatidylcholine (DPPC), or lecithin, is functionally the principle phospholipid.
Phosphatidylglycerol makes up 4-15% of the phospholipids; although it is a marker for lung
maturity, it is not necessary for normal lung function.

Bar chart demonstrates the composition of lung surfactant. About 1% of the 10% protein
component comprises surfactant apoproteins; the remaining proteins are derived from alveolar
exudate.
Among the 4 surfactant apoproteins identified, surfactant protein B (SP-B) and SP-C are 2 small
hydrophobic proteins that make up 2-4% of the surfactant mass and are present in commercially
available surfactant preparations. SP-B and SP-C work in concert to facilitate rapid adsorption and
spreading of DPPC as a monolayer to lower the surface tension at the alveolar air-fluid interface in
vivo during expiration, thus preventing atelectasis.
The SP-B gene is on human chromosome 2, and its primary translation product is 40 kd, which is
clipped to become an 8-kd protein in the type II cells before entering lamellar bodies to be
cosecreted with phospholipids. The SP-C gene is on chromosome 8; its primary translation
product, 22 kd, is processed to an extremely hydrophobic 4-kd protein that is associated with lipids
in lamellar bodies.
SP-A is an innate host defense, large molecular, hydrophilic (water soluble) lectin coded on
human chromosome 10 that regulates lung inflammation. SP-A contributes to the biophysical
properties of surfactant primarily by decreasing protein-mediated inhibition of surfactant function. It
binds to multiple organisms, such as group B streptococcus, Staphylococcus aureus, influenza
virus, adenovirus, herpes simplex type 1, and respiratory syncytial virus. SP-A facilitates
phagocytosis of pathogens by macrophages and their clearance from the airways. Mice that lack
SP-A have no tubular myelin and have normal lung function and surfactant metabolism, indicating
that SP-A is not a critical regulator of surfactant metabolism. Patients with SP-A deficiency have
not been described.
SP-D is also a hydrophilic protein of 43 kd that is a collectin with structural similarities to SP-A. It
has a collagenlike domain and a glycosylated region that gives it its lectinlike functions. SP-D is a
large multimer that is synthesized by type II alveolar cells and Clara cells in addition to other
epithelial cells in the body. It also binds pathogens and facilitates their clearance. The absence of
SP-D results in increased surfactant lipid pools in the airspaces and emphysema in mice. No
humans with SP-D deficiency have been described.
The components of pulmonary surfactant are synthesized in the Golgi apparatus of the
endoplasmic reticulum of the type II alveolar cell. (See the image below.)

Schematic show surfactant metabolism, with a single alveolus is shown and the location and
movement of surfactant components. Surfactant components are synthesized from precursors in
the endoplasmic reticulum and transported through the Golgi apparatus by multivesicular bodies.
Components are ultimately packaged in lamellar bodies, which are intracellular storage granules
for surfactant before its secretion. After secretion (exocytosis) into the liquid lining of the alveolus,
surfactant phospholipids are organized into a complex lattice called tubular myelin. Tubular myelin
is believed to generate the phospholipid that provides material for a monolayer at the air-liquid
interface in the alveolus, which lowers surface tension. Surfactant phospholipids and proteins are
subsequently taken back into type II cells, in the form of small vesicles, apparently by a specific
pathway that involves endosomes, and then are transported for storage into lamellar bodies for
recycling. Alveolar macrophages also take up some surfactant in the liquid layer. A single transit of
the phospholipid components of surfactant through the alveolar lumen normally requires a few
hours. The phospholipid in the lumen is taken back into type II cell and is reused 10 times before
being degraded. Surfactant proteins are synthesized in polyribosomes and extensively modified in
the endoplasmic reticulum, Golgi apparatus, and multivesicular bodies. Surfactant proteins are
detected in lamellar bodies or secretory vesicles closely associated with lamellar bodies before
they are secreted into the alveolus.
View Media Gallery
The components are packaged in multilamellar vesicles in the cytoplasm of the type II alveolar
cell. They are secreted by a process of exocytosis, the daily rate of which may exceed the weight
of the cell. Once secreted, the vesicles unwind to form bipolar monolayers of phospholipid
molecules that depend on the apoproteins SP-B and SP-C to properly configure in the alveolus.
The lipid molecules are enriched in dipalmitoyl acyl groups attached to a glycerol backbone that
pack tightly and generate low surface tension. Tubular myelin stores surfactant and depends on
SP-B. Corners of the myelin lattice appear to be glued together with the large apoprotein SP-A,
which may also have an important role in phagocytosis. Surfactant proteins are expressed in the
fetal lung with increasing gestational age.
Patient education
Because the risk of prematurity and respiratory distress syndrome is increased for subsequent
pregnancies, counsel the parents.
Education and counseling of parents, caregivers, and families of premature infants must be
undertaken as part of discharge planning. These individuals should be advised of the potential
problems infants with respiratory distress syndrome may encounter during and after their nursery
stay. Audiovisual aids and handouts supplement such education.

Etiology
In premature infants, respiratory distress syndrome develops because of impaired surfactant
synthesis and secretion leading to atelectasis, ventilation-perfusion (V/Q) inequality, and
hypoventilation with resultant hypoxemia and hypercarbia. Blood gases show respiratory
and metabolic acidosis that cause pulmonary vasoconstriction, resulting in impaired endothelial
and epithelial integrity with leakage of proteinaceous exudate and formation of hyaline membranes
(hence the name).
The relative deficiency of surfactant decreases lung compliance (see the image below) and
functional residual capacity, with increased dead space. The resulting large V/Q mismatch and
right-to-left shunt may involve as much as 80% of the cardiac output.

Bottom curve reflects findings from lungs obtained at postmortem from an infant with hyaline
membrane disease (HMD). Lungs with HMD require far more pressure than to achieve a given
volume of inflation than do lungs obtained from an infant dying of a nonrespiratory cause. Arrows
indicate inspiratory and expiratory limbs of the pressure-volume curves. Note the decreased lung
compliance and increased critical opening and closing pressures, respectively, in the premature
infant with HMD.
Hypoxia, acidosis, hypothermia, and hypotension may impair surfactant production and/or
secretion. In many neonates, oxygen toxicity with barotrauma and volutrauma in their structurally
immature lungs causes an influx of inflammatory cell, which exacerbates the vascular injury,
leading to bronchopulmonary dysplasia (BPD). Antioxidant deficiency and free-radical injury
worsen the injury.
Upon macroscopic evaluation, the lungs of affected newborns appear airless and ruddy (ie,
liverlike). Therefore, the lungs require an increased critical opening pressure to inflate. Diffuse
atelectasis of distal airspaces along with distension of distal airways and perilymphatic areas are
observed microscopically. Progressive atelectasis, barotrauma or volutrauma, and oxygen toxicity
damage endothelial and epithelial cells lining these distal airways, resulting in exudation of
fibrinous matrix derived from blood.
Hyaline membranes that line the alveoli (see the image below) may form within a half hour after
birth. In larger premature infants, the epithelium begins to heal at 36-72 hours after birth, and
endogenous surfactant synthesis begins. The recovery phase is characterized by regeneration of
alveolar cells, including type II cells, with a resultant increase in surfactant activity. The healing
process is complex.
A chronic process often ensues in infants who are extremely immature and critically ill and in
infants born to mothers with chorioamnionitis, resulting in BPD. In extremely premature infants, an
arrest in lung development often occurs during the saccular stage, resulting in chronic lung
disease termed "new" BPD.
Apoprotein deficiency
The hydrophobic SP-B and SP-C are essential for lung function and pulmonary homeostasis after
birth. These proteins enhance the spreading, adsorption, and stability of surfactant lipids required
to reduce surface tension in the alveolus. SP-B and SP-C participate in regulating intracellular and
extracellular processes critical for maintaining respiratory structure and function. [1]
SP-B deficiency is an inherited deficiency caused by a pretranslational mechanism implied by the
absence of messenger ribonucleic acid (mRNA). SP-B deficiency leads to death in term or near-
term neonates and clinically manifests as respiratory distress syndrome with pulmonary
hypertension, or congenital alveolar proteinosis. The genetic absence of SP-B is most often
caused by a 2-base pair insertion (121 ins 2) that produces a frame shift and premature terminal
signal, resulting in a complete absence of SP-B.
Approximately 15% of term infants who die of a syndrome similar to respiratory distress syndrome
have SP-B deficiency. The lack of SP-B causes a lack of normal lamellar bodies in type II cells, a
lack of SP-C, and the appearance of incompletely processed SP-C in the airspaces. These pro
SP-C forms are diagnostic of SP-B deficiency.
Analysis of lung tissue with immunologic and biologic methods reveals an absence of one of the
surfactant specific proteins, SP-B, and its mRNA. In an in-vitro study, critical structure and function
in the N-terminal region of pulmonary SP-B was noted. W9 is critical to optimal surface activity,
whereas prolines may promote a conformation that facilitates rapid insertion of the peptide into
phospholipid monolayers compressed to the highest pressures during compression-expansion
cycling.
Mutations of SP-B and SP-C cause acute respiratory distress syndrome and chronic lung disease
that may be related to the intracellular accumulation of injurious proteins, extracellular deficiency
of bioactive surfactant peptides, or both. Mutations in the gene for SP-C are a cause of familial
and sporadic interstitial lung disease and emphysema as patients age. Mutations in other genes
that cause protein misfolding and misrouting may contribute to the pathogenesis of chronic
interstitial lung disease.
Hydrophilic SP-A and SP-D are lectins. In vivo and in vitro studies provide compelling support for
SP-A and SP-D as mediators of various immune-cell functions. Studies have shown novel roles for
these proteins in the clearance of apoptotic cells, direct killing of microorganisms, and initiation of
parturition. None of the currently available surfactant preparations to treat respiratory distress
syndrome have SP-A and SP-D.
ABCA3 mutations
Mutations in the adenosine triphosphate (ATP)–binding casette gene (ABCA3) in newborns result
in fatal surfactant deficiency. ABCA3 is critical for proper formation of lamellar bodies and
surfactant function and may also be important for lung function in other pulmonary diseases.
Because it is closely related to the ABCA1 - and ABCA4 -encoded proteins that transport
 phospholipids in macrophages and photoreceptor cells, it may have a role in surfactant
phospholipid metabolism. [2]
The incidence of genetic abnormalities of pulmonary surfactant disorders is unknown. In a review
of 300 term infants presenting as severe respiratory distress syndrome, 14% had SP-B deficiency
and 14% had a deficiency of ABCA3.
Risk factors
The greatest risk factor for respiratory distress syndrome is prematurity, although the syndrome
does not occur in all premature newborns. Other risk factors include maternal diabetes, cesarean
delivery, and asphyxia. [3, 4]

2. Embriologi jantung, anatomi jantung

a. Chambers, valves, tissue layers, great vessel, coronary arteries
The heart has a middle muscular layer, the myocardium, made up of cardiac muscle cells, and an inner
lining called the endocardium. The inside of the heart (heart cavity) is divided into four chambers – two
atria and two ventricles – separated by cardiac valves that regulate the passage of blood.
The heart is enclosed in a sac, the pericardium, which protects it
and prevents it from over-expanding, anchoring it inside the thorax.
The pericardium is attached to the diaphragm and inner surface of
the sternum, and is made up of:
 The fibrous pericardium, composed of a loosely fitting
but dense layer of connective tissue;

 The serous pericardium or epicardium, composed of the

parietal and visceral layers;

 A film of serous fluid between the fibrous and serous

pericardium that allows them to glide smoothly against
each other.

Atria and ventricles

The atria receive blood returning to the heart, while the ventricles receive blood from the atria – via the
atrioventricular valves – and pumps it into the lungs and the rest of the body (Fig 2a). The left atrium (LA)
and left ventricle (LV) are separated from the right atria (RA) and right ventricle (RV) by a band of tissue
called the septum.
The RV does not need a huge amount of force to pump blood into the lungs, compared with the LV, which
has to pump blood into the rest of the body. The LV has a thicker wall and its cavity is circular, while the
RV cavity is crescent-shaped with a thinner wall

Cardiac valves
cardiac valves ensure a one-way system of blood flow. They have projections (cusps) held in place by
strong tendons (chordae tendinae) attached to the inner walls of the heart by small papillary muscles.
The RA and RV are separated by the tricuspid valve, which has three leaflets. The tricuspid valve allows
deoxygenated blood to move from the RA into the RV. From the RV, blood passes through the pulmonary
valve (situated between the RV and the pulmonary artery), allowing deoxygenated blood to enter the
lungs.
On the left side of the heart, oxygenated blood from the lungs enters the LA from the pulmonary vein. The
LA is separated from the LV by the mitral valve (also called bicuspid valve, as it has two leaflets and blood
flows through this valve into the LV. It then passes through the aortic valve into the aorta, which transports
oxygenated blood throughout the body.
Coronary circulation
The heart itself requires a richly oxygenated blood
supply to support its activity. This is delivered via the
right and left coronary arteries, which lie on the
epicardium and penetrate the myocardium with
deeper branches to supply this highly active layer of
muscle.
The right and left coronary arteries arise from vascular
openings at the base of the aorta, called the coronary
ostia. The left coronary artery runs towards the left
side of the heart, dividing into the left anterior
descending artery and the left circumflex artery. The
right coronary artery runs down the right side of the
heart dividing into the marginal artery (lateral part of the right-hand side of the heart) and posterior
descending artery (supplying the posterior part of the heart)
The coronary arteries provide an intermittent supply of blood to the heart, predominantly when the heart is
relaxed (during diastole), as the entrance to the coronary arteries is open at that point of the cardiac cycle
The venous drainage system of the heart uses the coronary veins, which follow a course similar to that
of the coronary arteries. The coronary sinus is a collection of coronary veins (small, middle, great and
oblique veins, left marginal vein and left posterior ventricular vein) that drain into the RA at the posterior
aspect of the heart. Two thirds of the cardiac venous blood is returned to the heart via the coronary sinus,
while one third is returned directly into the heart (with the anterior cardiac veins opening directly into the
RA and the smallest coronary veins into all four chambers).

b. Orientation within the mediastinum

Superior mediastinum ( mediastinum superius )
= Arcus aorta, trachea, vagus nerve, brachiocephalic
veins, phrenic nerve, SVC
Inferior mediastinum ( mediastinum inferius ), consists of :
o Anterior mediastinum ( mediastinum anterius )
= Thymus, Lymph nodes, internal thoracic vessels,
thyroid tissue
o Middle mediastinum ( mediastinum medius )
= pericardium, HEART, pulmonary trunk, ascending
aorta, SVC, IVC
o Posterior mediastinum ( mediastinum posterius )
= esophagus, descending aorta, azygos, hemiazygos veins, vagi.
Mediastinum divided into superior mediastinum and inferior mediastinum
= in rib 2 (between T4 and T5)
c. Embryological development
The embryological development of the cardiovascular
system begins with the migration of cardiac progenitor
cells that reside in the epiblast, just lateral to the
primitive streak. These cardiac progenitor cells
eventually develop into cardiac myoblasts. Within this
same splanchnic layer of the mesoderm, so-called
“blood islands” eventually undergo a period of
vasculogenesis to form vascular
structures. Coalescence(peleburan/penggabungan)
of the blood islands eventually forms a region known
as the cardiogenic field. The cardiogenic field is initially
horseshoe-shaped and surrounded by cardiac
myoblasts with the apex of the cardiogenic field
eventually developing into primitive ventricles along
with their respective outflow tracts. Eventually, the cardiogenic field changes its configuration by
cephalocaudal rotation. By doing so, it forms a primitive heart tube continuous with vascular structures

By

approximately
day 22-23, the heart tube elongates and alters its
configuration again, forming a cardiac loop. The cardiac
loop forms when the cranial aspect of the heart tube bends
ventrocaudally and to the right while the caudal aspect of
the heart tube bends toward the dorsocranial aspect and
towards the left. The formation of the cardiac loop takes
approximately five days, nearing completion by day 28. The
proximal aspect of the heart tube forms the bulbus cordis,
which develops into the trabeculated parts of the right
ventricle. The middle segment of the heart tube is the
conus cordis and is the precursor for the ventricular outflow tracts. The distal portion of the heart tube is
referred to as the truncus arteriosus. The truncus arteriosus gives rise to the proximal portion of the aorta
and pulmonary artery.
Prior to the end of the cardiac loop formation, the heart tube is essentially smooth-walled. Near the end of
the loop formation, however, trabeculated regions begin to form, and these trabeculated regions serve as
primitive ventricles.
The septa of the heart typically form between the 27th and
37th days of development via fusion of tissue
masses. These tissue masses are known as the
endocardial cushions, and they contribute to the formation of
the atrial/ventricular septa, the AV canals and valves, and
the aortic/pulmonary channels. By the end of the 4th
developmental week, the roof of the common atrium
develops a crest-like structure known as the septum
primum. The septum primum is sickle-shaped, and the two
inferior limbs of the septum primum migrate toward the
endocardial cushion. As the septum primum and the
endocardial cushions do not fully fuse initially, there remains
an opening called the ostium primum.
The endocardial cushions eventually fuse with the septum
primum. Physiologic apoptosis produces perforations in the
septum primum which ultimately coalesce to form a structure
called the ostium secundum. The ostium secundum allows
for blood from the right primitive atrium to the left primitive
atrium. Eve ntually, expansion of the right atrium occurs, during
which a new fold develops in the right atrium. This new fold of
tissue is called the septum secundum and it never completely
partitions the atrium. The anterior aspect of the septum
secundum extends inferiorly towards the fused endocardial
cushions.
The septum secundum forms a crescent-shaped configuration that incompletely overlaps the ostium
secundum. The remaining opening is the foramen ovale, which is one of two fetal structures responsible
for directing blood flow from the developing lungs (the other structure is the ductus arteriosus). After
overlapping of the septum secundum over the ostium secundum, the septum primum gradually
disappears, its remnant forming the valve of the foramen ovale. After birth, the increased oxygen tension
taken from the newborn’s first breath allows for increased blood into the lungs. The increased blood flow
into the lungs increases the left interatrial pressure, allowing for blood to close the valve of the foramen
ovale against the septum secundum.
By the end of the 4th week of gestation, the atrioventricular canal develops two atrioventricular cushions
along the superior and inferior borders in addition to two lateral cushions. The superior and inferior
endocardial cushions eventually project into the lumen and eventually fuse, although the lateral cushions
do not participate in this process. The result is the division of the atrioventricular canal into two distinct
orifices (the left atrioventricular canal and the right atrioventricular canal). Mesenchymal tissue surrounds
the peripheral edges of each atrioventricular canal. This mesenchymal tissue eventually thins to form
atrioventricular valves. The valves themselves connect to thick papillary muscles via the chordae tendinae.
The trabecular meshwork is an essential morphological development.
During the 5th week of development, swellings appear in the truncus. The right superior truncus swelling
migrates towards the left while the left inferior truncus swelling moves towards the right. The truncus
swellings eventually rotate around each other to fuse, forming the aorticopulmonary septum. The
formation of the septum divides the truncus into two channels: the aortic channel and the pulmonary
channel. As the truncus swellings begin to form, the walls of the conus cordis also start to develop
structures called the conus swellings. The conus swellings grow toward one another to eventually fuse,
forming the primitive outflow tracts. The septum divides the conus cordis into two portions: an anterolateral
and a posteromedial portion with the anterolateral portion becoming the outflow tract of the right ventricle
and the posteromedial portion becoming the outflow tract of the left ventricle. The development of the
semilunar valves begins near the completion of the truncus partitioning, starting with primordial semilunar
valves located on the truncal swellings. These primordial semilunar valves start off as tubercles on the
main truncus swellings and eventually thin to become the semilunar valves. Septum formation of the
ventricles has a somewhat different approach from the developmental standpoint, as opposed to the
atria. The ventricle walls start to expand by approximately the 4th week, with gradual apposition and
merger of the medial ventricular walls, forming a muscular interventricular septum. The membranous part
of the interventricular septum forms from the complete closure of the interventricular foramen, which
closes from tissue growth from the endocardial cushions.The pacemaker of the primitive heart tube is
located in the caudal portion. Later in development, the sinus venosus (a location in the mammalian
embryological heart between the two venae) assumes the role of the pacemaker of the embryonic
heart. Its incorporation into the right atrium serves as the origin of the sinoatrial node

Truncus arteriosus : aorta, arteri pulmonal

Bulbus kordis : jalur keluar ventrikel
Ventrikel primitive : jalur masuk ventrikel
Atrium primitive : atrium kanan dan kiri
Sinus venosus : bagian dari atrium kanan

3. Hypovolemic, organ apa yang terkena efeknya

duluan
4. Coarctation
Koarktasio aorta terdiri dari penyempitan lumen aorta.
Kelainan jantung yang sering menyertai adalah aorta bicuspid valve. Biasanya koarktasio aorta terjadi pada
pasien sindrom Turner (45, XO).
2 kategori pada koarktasio berdasarkan letak penyempitan aorta dengan ductus arteriosus :
a. Preduktal (infantile)
b. Postduktal (tipe dewasa)
Sekarang lebih sering juxtaduktal (dekat dengan ductus)
A. PATOFISIOLOGI
Karena penyempitan aorta pada koarktasio, ventrikel kiri mengalami peningkatan afterload. Aliran darah
ke kepala dan ekstrimitas superior terjamin karena PD yang suplai ini berasal dari aorta branch yang
letaknya diatas obstruksi. Aliran darah ke aorta descendens dan ekstrimitas inferior berkurang.
Kompensasi :
1. Hipertrofi ventrikel kiri
2. Dilatasi PD kolateral dari arteri intercostal yang memintas koarktasio dan menyediakan darah ke
aorta descendens yang lebih distal. PD kolateral akan membesar dan menyebabkan erosi bagian
bawah tulang rusuk.
B. GEJALA
- Gagal jantung setelah lahir (koarktasio berat)
- Sianosis ekstrimitas bawah pada bayi (differential cyanosis) jika ductus arteriosus tidak konstriksi
dan tetap buka
- Setengah tubuh perfusinya baik, setengah tubuh sianosis
- Jika koarktasio tidak berat, tidak ada gejala atau mengalami kelemahan ringan atau nyeri di
ekstrimitas bawah setelah olahraga (claudication).
- Ditemukan hipertensi ekstremitas superior
 C. STUDI DIAGNOSTIK
1. Rontgen menunjukkan notching permukaan inferior rusuk posterior karena pembesaran pembuluh
darah intercostal yang menyuplai sirkulasi kolateral ke aorta descendens.
2. EKG menandakan hipertrofi ventrikel kiri akibat beban tekanan pada ruangan tsb.
3. Ekokardiografi Doppler Test menilai gradien tekanan pada lesi.
4. MRI atau CT memperlihatkan secara detail panjang dan derajat keparahan koarktasio.
D. TREATMENT
- Neonatus, koarktasio berat : infus prostaglandin diberikan agar ductus arteriosus tetap
terbukamempertahankan aliran darah tetap ke aorta descendens
- Eksisi segmen aorta yang menyempit kemudian direanastomosis ujung ke ujung (end to end)
- Koreksi langsung pada aorta, menggunakan material patch sintetik.
- Intervensi transkateter (dilatasi balon dengan atau tanpa penempatan stent)
5. Suara jantung (S1, S2, S3..)
6. Systolic thrill and murmur
Diastole and systole affect a person's blood pressure differently, as follows:
 When the heart pushes blood around the body during systole, the pressure placed on the
vessels increases. This is called systolic pressure.

 When the heart relaxes between beats and refills with blood, the blood pressure drops. This is
called diastolic pressure.

systolic thrill one felt over the precordium during ventricular systole in aortic stenosis, pulmonary stenosi
s, and ventricular septal defect.
Almost any murmur may be loud enough to be accompanied by a thrill, but
in a few conditions they are very common. A systolic thrill over the aortic
area and transmitted into the carotid arteries is common in aortic stenosis,
Systolic heart murmurs are heart murmurs heard during systole.
They can be classified by when the murmur begins and ends,
between S1 and S2.
Many involve stenosis of the semilunar valves or regurgitation of
the atrioventricular valves.
Abnormal heart murmurs
The most common cause of abnormal murmurs in children is when babies
are born with structural problems of the heart (congenital heart defects).
Common congenital defects that cause heart murmurs include:
 Holes in the heart or cardiac shunts. Known as septal
defects, holes in the heart may or may not be serious,
depending on the size of the hole and its location.

Cardiac shunts occur when there's an abnormal blood flow between the heart chambers or blood vessels,
which may lead to a heart murmur.
 Heart valve abnormalities. Congenital heart valve abnormalities are present at birth, but
sometimes aren't discovered until much later in life. Examples include valves that don't allow
enough blood thro

7. Pansystolic murmur, gallop

A ventricular gallop sound is an extra heart sound. There are two types of gallop sounds, S3 and S4.
S3 gallop is a low frequency, early to mid-diastolic sound.
In the normal heart during normal sinus rhythm, diastolic filling of the ventricle across the atrioventricular valves occurs
in two phases, early and atrial filling. There are characterized by Doppler echocardiography:
E wave is the characteristic wave seen on Doppler related to passive filling of the ventricle.
A wave is active filling with atrial systole seen on Doppler.
E and A waves representing mitral flow in a healthy heart (E > A). E wave is classically greater than A wave since
passive filling encompasses 80 %. In conditions that limit ventricular compliance two abnormalities are possible:
 reversal – in which the A wave is greater than the E wave. This indicates slow filling caused by older age, hypertension,
left ventricular hypertrophy (LVH), or diastolic dysfunction.
exaggeration of normal – a tall, thin E wave with a small or absent A wave. This indicates restrictive cardiomyopathy,
constrictive pericarditis, or infiltrative cardiac disease [1–3].

8. VT, VF, AF, asystole ECG

1. Ventricular Tachycardia (VT)
Adanya daerah miokard iskemik menyebabkan putaran balik konduksi impuls sehingga terjadi depolarisasi
ventrikel berulang secara cepat. Takikardi ventrikel mempunyai karakteristik sebagai berikut: (Brunner &
Suddarth, 2002)
 Frekuensi : 150-200 x/menit
 Gelombang P: biasanya tenggelam dalam kompleks QRS; bila terlihat, tidak selalu mempunyai pola
yang sesuai dengan QRS. Kontraksi ventrikel tidak berhubungan dengan kontraksi atrium.
 Kompleks QRS: mempunyai konfigurasi yang sama dengan PVC-lebar dan aneh, dengan gelombang
T terbalik. Denyut ventrikel dapat bergabung dengan QRS normal, menghasilkan denyut gabungan
 Hantaran: berasal dari ventrikel, dengan kemungkinan hantaran retrograde ke jaringan penyambung
dan atrium
 Iram: biasanya regular, tetapi dapat juga terjadi takikardi ventrikel irregular

Ventricular Tachycardia (VT)

2. Ventrikel Fibrilasi (VF)

Adalah gambaran bergetarnya ventrikel. Hal ini disebabkan karena banyaknya tempat di ventrikel yang
memunculkan impuls, sehingga sel jantung tidak sempat berdepolarisasi dan repolarisasi sempurna.

Ventrikel Fibrilasi (VF)

3. Ventrikel Ekstra Sistol (VES)

Adalah gelombang ventrikel yang tiba-tiba muncul pada gelombang sinus. Ini muncul karena pacemaker
ventrikel tiba-tiba lebih kuat dari NSA dalam memproduksi impuls listrik. Jika ada Ekstra Sistole yang
muncul, dimana R dari Ekstra Sistol tersebut berada di gelombang T sebelumnya, maka ini disebut fenomena
R on T, dan ini ganas. Macam-macam VES :
1. Ventrikel Ekstra Sistol “Uniform”

Adalah Ventrikel ekstra systole yang bentuknya serupa dalam lead yang sama. Jika berbeda bentuk tetapi
dengan lead yang berbeda, belum tetu bentuk Uniform. VES Uniform disebut juga VES Unifokal.

Ventrikel Ekstra Sistol “Uniform”

2. Ventrikel Ekstra Sistol “Multiform”

Adalah Ventrikel Ekstra Sistol yang memiliki bentuk beragam dalam lead yang sama. Disebut juga VES
Multifokal. Ini menunjukan ada beberapa sumber impuls yang berbeda di Ventrikel.

Ventrikel Ekstra Sistol “Multiform”

3. Ventrikel Ekstra Sistol “Bigemini”

Bigemini maksudnya, setiap satu kompleks normal diikuti satu VES.

Ventrikel Ekstra Sistol “Bigemini"

4. Ventrikel Ekstra Sistol “Trigemini”
Trigemini artinya setiap dua kompleks normal diikuti satu VES.

Ventrikel Ekstra Sistol “Trigemini”

5. Ventrikel Ekstra Sistol “Couplet”

Couplet artinya setelah kompleks normal muncul dua VES sekaligus.
 Rabu, 18 september 2019

1. Cardiac Physiology
Learning Objectives
By the end of this section, you will be able to:
 Relate heart rate to cardiac output
 Describe the effect of exercise on heart rate
 Identify cardiovascular centers and cardiac reflexes that regulate heart function
 Describe factors affecting heart rate
 Distinguish between positive and negative factors that affect heart contractility
 Summarize factors affecting stroke volume and cardiac output
 Describe the cardiac response to variations in blood flow and pressure

The autorhythmicity inherent in cardiac cells keeps the heart beating at a regular pace; however, the heart is regulated by and
responds to outside influences as well. Neural and endocrine controls are vital to the regulation of cardiac function. In addition, the
heart is sensitive to several environmental factors, including electrolytes.

Resting Cardiac Output

Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle in one minute. To calculate this value,
multiply stroke volume (SV), the amount of blood pumped by each ventricle, by heart rate (HR), in contractions per minute (or beats per
minute, bpm). It can be represented mathematically by the following equation:
CO = HR × SV
SV is normally measured using an echocardiogram to record EDV and ESV, and calculating the difference: SV = EDV – ESV. SV can also be
measured using a specialized catheter, but this is an invasive procedure and far more dangerous to the patient. A mean SV for a resting 70-kg
(150-lb) individual would be approximately 70 mL. There are several important variables, including size of the heart, physical and mental
condition of the individual, sex, contractility, duration of contraction, preload or EDV, and afterload or resistance. Normal range for SV would
be 55–100 mL. An average resting HR would be approximately 75 bpm but could range from 60–100 in some individuals.
Using these numbers, the mean CO is 5.25 L/min, with a range of 4.0–8.0 L/min. Remember, however, that these numbers refer to CO from
each ventricle separately, not the total for the heart. Factors influencing CO are summarized in Figure 1.

Figure 1. Major Factors Influencing Cardiac Output. Cardiac output is influenced by heart rate and stroke volume, both of which are also
variable.
SVs are also used to calculate ejection fraction, which is the portion of the blood that is pumped or ejected from the heart with each contraction.
To calculate ejection fraction, SV is divided by EDV. Despite the name, the ejection fraction is normally expressed as a percentage. Ejection
fractions range from approximately 55–70 percent, with a mean of 58 percent.

Exercise and Maximum Cardiac Output

In healthy young individuals, HR may increase to 150 bpm during exercise. SV can also increase from 70 to approximately 130 mL due to
increased strength of contraction. This would increase CO to approximately 19.5 L/min, 4–5 times the resting rate. Top cardiovascular athletes
can achieve even higher levels. At their peak performance, they may increase resting CO by 7–8 times.
Since the heart is a muscle, exercising it increases its efficiency. The difference between maximum and resting CO is known as the cardiac
reserve. It measures the residual capacity of the heart to pump blood.

Heart Rates
HRs vary considerably, not only with exercise and fitness levels, but also with age. Newborn resting HRs may be 120 bpm. HR gradually
decreases until young adulthood and then gradually increases again with age.
Maximum HRs are normally in the range of 200–220 bpm, although there are some extreme cases in which they may reach higher levels. As one
ages, the ability to generate maximum rates decreases. This may be estimated by taking the maximal value of 220 bpm and subtracting the
individual’s age. So a 40-year-old individual would be expected to hit a maximum rate of approximately 180, and a 60-year-old person would
achieve a HR of 160.

Disorders of the Heart: Abnormal Heart Rates

For an adult, normal resting HR will be in the range of 60–100 bpm. Bradycardia is the condition in which resting rate drops below 60 bpm, and
tachycardia is the condition in which the resting rate is above 100 bpm. Trained athletes typically have very low HRs. If the patient is not
exhibiting other symptoms, such as weakness, fatigue, dizziness, fainting, chest discomfort, palpitations, or respiratory distress, bradycardia is
not considered clinically significant. However, if any of these symptoms are present, they may indicate that the heart is not providing sufficient
oxygenated blood to the tissues. The term relative bradycardia may be used with a patient who has a HR in the normal range but is still
suffering from these symptoms. Most patients remain asymptomatic as long as the HR remains above 50 bpm.
Bradycardia may be caused by either inherent factors or causes external to the heart. While the condition may be inherited, typically it is
acquired in older individuals. Inherent causes include abnormalities in either the SA or AV node. If the condition is serious, a pacemaker may be
required. Other causes include ischemia to the heart muscle or diseases of the heart vessels or valves. External causes include metabolic
disorders, pathologies of the endocrine system often involving the thyroid, electrolyte imbalances, neurological disorders including inappropriate
autonomic responses, autoimmune pathologies, over-prescription of beta blocker drugs that reduce HR, recreational drug use, or even prolonged
bed rest. Treatment relies upon establishing the underlying cause of the disorder and may necessitate supplemental oxygen.
Tachycardia is not normal in a resting patient but may be detected in pregnant women or individuals experiencing extreme stress. In the latter
case, it would likely be triggered by stimulation from the limbic system or disorders of the autonomic nervous system. In some cases,
tachycardia may involve only the atria. Some individuals may remain asymptomatic, but when present, symptoms may include dizziness,
shortness of breath, lightheadedness, rapid pulse, heart palpations, chest pain, or fainting (syncope). While tachycardia is defined as a HR above
100 bpm, there is considerable variation among people. Further, the normal resting HRs of children are often above 100 bpm, but this is not
considered to be tachycardia Many causes of tachycardia may be benign, but the condition may also be correlated with fever, anemia, hypoxia,
hyperthyroidism, hypersecretion of catecholamines, some cardiomyopathies, some disorders of the valves, and acute exposure to radiation.
Elevated rates in an exercising or resting patient are normal and expected. Resting rate should always be taken after recovery from exercise.
Treatment depends upon the underlying cause but may include medications, implantable cardioverter defibrillators, ablation, or surgery.

Correlation Between Heart Rates and Cardiac Output

Initially, physiological conditions that cause HR to increase also trigger an increase in SV. During exercise, the rate of blood returning to the
heart increases. However as the HR rises, there is less time spent in diastole and consequently less time for the ventricles to fill with blood. Even
though there is less filling time, SV will initially remain high. However, as HR continues to increase, SV gradually decreases due to decreased
filling time. CO will initially stabilize as the increasing HR compensates for the decreasing SV, but at very high rates, CO will eventually
decrease as increasing rates are no longer able to compensate for the decreasing SV. Consider this phenomenon in a healthy young individual.
Initially, as HR increases from resting to approximately 120 bpm, CO will rise. As HR increases from 120 to 160 bpm, CO remains stable, since
the increase in rate is offset by decreasing ventricular filling time and, consequently, SV. As HR continues to rise above 160 bpm, CO actually
decreases as SV falls faster than HR increases. So although aerobic exercises are critical to maintain the health of the heart, individuals are
cautioned to monitor their HR to ensure they stay within the target heart rate range of between 120 and 160 bpm, so CO is maintained. The
target HR is loosely defined as the range in which both the heart and lungs receive the maximum benefit from the aerobic workout and is
dependent upon age.

Cardiovascular Centers
Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata (Figure 2). The cardioaccelerator
regions stimulate activity via sympathetic stimulation of the cardioaccelerator nerves, and the cardioinhibitory centers decrease heart activity via
parasympathetic stimulation as one component of the vagus nerve, cranial nerve X. During rest, both centers provide slight stimulation to the
heart, contributing to autonomic tone. This is a similar concept to tone in skeletal muscles. Normally, vagal stimulation predominates as, left
unregulated, the SA node would initiate a sinus rhythm of approximately 100 bpm.
Both sympathetic and parasympathetic stimulations flow through a paired complex network of nerve fibers known as the cardiac plexus near
the base of the heart. The cardioaccelerator center also sends additional fibers, forming the cardiac nerves via sympathetic ganglia (the cervical
ganglia plus superior thoracic ganglia T1–T4) to both the SA and AV nodes, plus additional fibers to the atria and ventricles. The ventricles are
more richly innervated by sympathetic fibers than parasympathetic fibers. Sympathetic stimulation causes the release of the neurotransmitter
norepinephrine (NE) at the neuromuscular junction of the cardiac nerves. NE shortens the repolarization period, thus speeding the rate of
depolarization and contraction, which results in an increase in HR. It opens chemical- or ligand-gated sodium and calcium ion channels,
allowing an influx of positively charged ions.
NE binds to the beta-1 receptor. Some cardiac medications (for example, beta blockers) work by blocking these receptors, thereby slowing HR
and are one possible treatment for hypertension. Overprescription of these drugs may lead to bradycardia and even stoppage of the heart.

Figure 2. Autonomic Innervation of the Heart. Cardioaccelerator and cardioinhibitory areas are components of the paired cardiac centers
located in the medulla oblongata of the brain. They innervate the heart via sympathetic cardiac nerves that increase cardiac activity and vagus
(parasympathetic) nerves that slow cardiac activity.

Parasympathetic stimulation originates from the cardioinhibitory region with impulses traveling via the vagus nerve (cranial nerve X). The vagus
nerve sends branches to both the SA and AV nodes, and to portions of both the atria and ventricles. Parasympathetic stimulation releases the
neurotransmitter acetylcholine (ACh) at the neuromuscular junction. ACh slows HR by opening chemical- or ligand-gated potassium ion
channels to slow the rate of spontaneous depolarization, which extends repolarization and increases the time before the next spontaneous
depolarization occurs. Without any nervous stimulation, the SA node would establish a sinus rhythm of approximately 100 bpm. Since resting
rates are considerably less than this, it becomes evident that parasympathetic stimulation normally slows HR. This is similar to an individual
driving a car with one foot on the brake pedal. To speed up, one need merely remove one’s foot from the break and let the engine increase speed.
In the case of the heart, decreasing parasympathetic stimulation decreases the release of ACh, which allows HR to increase up to approximately
100 bpm. Any increases beyond this rate would require sympathetic stimulation. Figure 3 illustrates the effects of parasympathetic and
sympathetic stimulation on the normal sinus rhythm.
 Figure 3. Effects of Parasympathetic and Sympathetic Stimulation on Normal Sinus Rhythm. The wave of depolarization in a normal sinus
rhythm shows a stable resting HR. Following parasympathetic stimulation, HR slows. Following sympathetic stimulation, HR increases.

Input to the Cardiovascular Center

The cardiovascular center receives input from a series of visceral receptors with impulses traveling through visceral sensory fibers within the
vagus and sympathetic nerves via the cardiac plexus. Among these receptors are various proprioreceptors, baroreceptors, and chemoreceptors,
plus stimuli from the limbic system. Collectively, these inputs normally enable the cardiovascular centers to regulate heart function precisely, a
process known as cardiac reflexes. Increased physical activity results in increased rates of firing by various proprioreceptors located in muscles,
joint capsules, and tendons. Any such increase in physical activity would logically warrant increased blood flow. The cardiac centers monitor
these increased rates of firing, and suppress parasympathetic stimulation and increase sympathetic stimulation as needed in order to increase
blood flow.
Similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including
pulmonary vessels and the right side of the heart itself. Rates of firing from the baroreceptors represent blood pressure, level of physical activity,
and the relative distribution of blood. The cardiac centers monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called
the baroreceptor reflex. With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centers decrease
sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases,
and the cardiac centers increase sympathetic stimulation and decrease parasympathetic stimulation.
There is a similar reflex, called the atrial reflex or Bainbridge reflex, associated with varying rates of blood flow to the atria. Increased venous
return stretches the walls of the atria where specialized baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing
and as they stretch due to the increased blood pressure, the cardiac center responds by increasing sympathetic stimulation and inhibiting
parasympathetic stimulation to increase HR. The opposite is also true.
Increased metabolic byproducts associated with increased activity, such as carbon dioxide, hydrogen ions, and lactic acid, plus falling oxygen
levels, are detected by a suite of chemoreceptors innervated by the glossopharyngeal and vagus nerves. These chemoreceptors provide feedback
to the cardiovascular centers about the need for increased or decreased blood flow, based on the relative levels of these substances.
The limbic system can also significantly impact HR related to emotional state. During periods of stress, it is not unusual to identify higher than
normal HRs, often accompanied by a surge in the stress hormone cortisol. Individuals experiencing extreme anxiety may manifest panic attacks
with symptoms that resemble those of heart attacks. These events are typically transient and treatable. Meditation techniques have been
developed to ease anxiety and have been shown to lower HR effectively. Doing simple deep and slow breathing exercises with one’s eyes closed
can also significantly reduce this anxiety and HR.

Disorders of the Heart: Broken Heart Syndrome

Extreme stress from such life events as the death of a loved one, an emotional break up, loss of income, or foreclosure of a home may lead to a
condition commonly referred to as broken heart syndrome. This condition may also be called Takotsubo cardiomyopathy, transient apical
ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, Gebrochenes-Herz syndrome, and stress
cardiomyopathy. The recognized effects on the heart include congestive heart failure due to a profound weakening of the myocardium not
related to lack of oxygen. This may lead to acute heart failure, lethal arrhythmias, or even the rupture of a ventricle. The exact etiology is not
known, but several factors have been suggested, including transient vasospasm, dysfunction of the cardiac capillaries, or thickening of the
myocardium—particularly in the left ventricle—that may lead to the critical circulation of blood to this region. While many patients survive the
initial acute event with treatment to restore normal function, there is a strong correlation with death. Careful statistical analysis by the Cass
Business School, a prestigious institution located in London, published in 2008, revealed that within one year of the death of a loved one,
women are more than twice as likely to die and males are six times as likely to die as would otherwise be expected.

Other Factors Influencing Heart Rate

Using a combination of autorhythmicity and innervation, the cardiovascular center is able to provide relatively precise control over HR.
However, there are a number of other factors that have an impact on HR as well, including epinephrine, NE, and thyroid hormones; levels of
various ions including calcium, potassium, and sodium; body temperature; hypoxia; and pH balance (Table 1 and Table 2). After reading this
section, the importance of maintaining homeostasis should become even more apparent.
Major Factors Increasing Heart Rate and Force of Contraction (Table 1)

Factor Effect

Cardioaccelerator nerves Release of norepinephrine

Proprioreceptors Increased rates of firing during exercise

 Major Factors Increasing Heart Rate and Force of Contraction (Table 1)

Factor Effect

Chemoreceptors Decreased levels of O2; increased levels of H+, CO2, and lactic acid

Baroreceptors Decreased rates of firing, indicating falling blood volume/pressure

Limbic system Anticipation of physical exercise or strong emotions

Catecholamines Increased epinephrine and norepinephrine

Thyroid hormones Increased T3 and T4

Calcium Increased Ca2+

Potassium Decreased K+

Sodium Decreased Na+

Body temperature Increased body temperature

Nicotine and caffeine Stimulants, increasing heart rate

Factors Decreasing Heart Rate and Force of Contraction (Table 2)

Factor Effect

Cardioinhibitor nerves (vagus) Release of acetylcholine

Proprioreceptors Decreased rates of firing following exercise

Chemoreceptors Increased levels of O2; decreased levels of H+ and CO2

Baroreceptors Increased rates of firing, indicating higher blood volume/pressure

Limbic system Anticipation of relaxation

Catecholamines Decreased epinephrine and norepinephrine

Thyroid hormones Decreased T3 and T4

Calcium Decreased Ca2+

Potassium Increased K+

Sodium Increased Na+

Body temperature Decrease in body temperature

Epinephrine and Norepinephrine
The catecholamines, epinephrine and NE, secreted by the adrenal medulla form one component of the extended fight-or-flight mechanism. The
other component is sympathetic stimulation. Epinephrine and NE have similar effects: binding to the beta-1 receptors, and opening sodium and
calcium ion chemical- or ligand-gated channels. The rate of depolarization is increased by this additional influx of positively charged ions, so the
threshold is reached more quickly and the period of repolarization is shortened. However, massive releases of these hormones coupled with
sympathetic stimulation may actually lead to arrhythmias. There is no parasympathetic stimulation to the adrenal medulla.
Thyroid Hormones
In general, increased levels of thyroid hormone, or thyroxin, increase cardiac rate and contractility. The impact of thyroid hormone is typically
of a much longer duration than that of the catecholamines. The physiologically active form of thyroid hormone, T 3 or triiodothyronine, has been
shown to directly enter cardiomyocytes and alter activity at the level of the genome. It also impacts the beta adrenergic response similar to
epinephrine and NE described above. Excessive levels of thyroxin may trigger tachycardia.
Calcium
Calcium ion levels have great impacts upon both HR and contractility; as the levels of calcium ions increase, so do HR and contractility. High
levels of calcium ions (hypercalcemia) may be implicated in a short QT interval and a widened T wave in the ECG. The QT interval represents
the time from the start of depolarization to repolarization of the ventricles, and includes the period of ventricular systole. Extremely high levels
of calcium may induce cardiac arrest. Drugs known as calcium channel blockers slow HR by binding to these channels and blocking or slowing
the inward movement of calcium ions.
Caffeine and Nicotine
Caffeine and nicotine are not found naturally within the body. Both of these nonregulated drugs have an excitatory effect on membranes of
neurons in general and have a stimulatory effect on the cardiac centers specifically, causing an increase in HR. Caffeine works by increasing the
rates of depolarization at the SA node, whereas nicotine stimulates the activity of the sympathetic neurons that deliver impulses to the heart.
Although it is the world’s most widely consumed psychoactive drug, caffeine is legal and not regulated. While precise quantities have not been
established, “normal” consumption is not considered harmful to most people, although it may cause disruptions to sleep and acts as a diuretic. Its
consumption by pregnant women is cautioned against, although no evidence of negative effects has been confirmed. Tolerance and even
physical and mental addiction to the drug result in individuals who routinely consume the substance.
Nicotine, too, is a stimulant and produces addiction. While legal and nonregulated, concerns about nicotine’s safety and documented links to
respiratory and cardiac disease have resulted in warning labels on cigarette packages.

Factors Decreasing Heart Rate

HR can be slowed when a person experiences altered sodium and potassium levels, hypoxia, acidosis, alkalosis, and hypothermia (see Table 1).
The relationship between electrolytes and HR is complex, but maintaining electrolyte balance is critical to the normal wave of depolarization. Of
the two ions, potassium has the greater clinical significance. Initially, both hyponatremia (low sodium levels) and hypernatremia (high sodium
levels) may lead to tachycardia. Severely high hypernatremia may lead to fibrillation, which may cause CO to cease. Severe hyponatremia leads
to both bradycardia and other arrhythmias. Hypokalemia (low potassium levels) also leads to arrhythmias, whereas hyperkalemia (high
potassium levels) causes the heart to become weak and flaccid, and ultimately to fail.
Heart muscle relies exclusively on aerobic metabolism for energy. Hypoxia (an insufficient supply of oxygen) leads to decreasing HRs, since
metabolic reactions fueling heart contraction are restricted.
Acidosis is a condition in which excess hydrogen ions are present, and the patient’s blood expresses a low pH value. Alkalosis is a condition in
which there are too few hydrogen ions, and the patient’s blood has an elevated pH. Normal blood pH falls in the range of 7.35–7.45, so a number
lower than this range represents acidosis and a higher number represents alkalosis. Recall that enzymes are the regulators or catalysts of virtually
all biochemical reactions; they are sensitive to pH and will change shape slightly with values outside their normal range. These variations in pH
and accompanying slight physical changes to the active site on the enzyme decrease the rate of formation of the enzyme-substrate complex,
subsequently decreasing the rate of many enzymatic reactions, which can have complex effects on HR. Severe changes in pH will lead to
denaturation of the enzyme.
The last variable is body temperature. Elevated body temperature is called hyperthermia, and suppressed body temperature is called
hypothermia. Slight hyperthermia results in increasing HR and strength of contraction. Hypothermia slows the rate and strength of heart
contractions. This distinct slowing of the heart is one component of the larger diving reflex that diverts blood to essential organs while
submerged. If sufficiently chilled, the heart will stop beating, a technique that may be employed during open heart surgery. In this case, the
patient’s blood is normally diverted to an artificial heart-lung machine to maintain the body’s blood supply and gas exchange until the surgery is
complete, and sinus rhythm can be restored. Excessive hyperthermia and hypothermia will both result in death, as enzymes drive the body
systems to cease normal function, beginning with the central nervous system.

Stroke Volume
Many of the same factors that regulate HR also impact cardiac function by altering SV. While a number of variables are involved, SV is
ultimately dependent upon the difference between EDV and ESV. The three primary factors to consider are preload, or the stretch on the
ventricles prior to contraction; the contractility, or the force or strength of the contraction itself; and afterload, the force the ventricles must
generate to pump blood against the resistance in the vessels. These factors are summarized in Table 1 and Table 2.

Preload
Preload is another way of expressing EDV. Therefore, the greater the EDV is, the greater the preload is. One of the primary factors to consider
is filling time, or the duration of ventricular diastole during which filling occurs. The more rapidly the heart contracts, the shorter the filling time
becomes, and the lower the EDV and preload are. This effect can be partially overcome by increasing the second variable, contractility, and
raising SV, but over time, the heart is unable to compensate for decreased filling time, and preload also decreases.
With increasing ventricular filling, both EDV or preload increase, and the cardiac muscle itself is stretched to a greater degree. At rest, there is
little stretch of the ventricular muscle, and the sarcomeres remain short. With increased ventricular filling, the ventricular muscle is increasingly
stretched and the sarcomere length increases. As the sarcomeres reach their optimal lengths, they will contract more powerfully, because more of
the myosin heads can bind to the actin on the thin filaments, forming cross bridges and increasing the strength of contraction and SV. If this
process were to continue and the sarcomeres stretched beyond their optimal lengths, the force of contraction would decrease. However, due to
the physical constraints of the location of the heart, this excessive stretch is not a concern.
The relationship between ventricular stretch and contraction has been stated in the well-known Frank-Starling mechanism or simply Starling’s
Law of the Heart. This principle states that, within physiological limits, the force of heart contraction is directly proportional to the initial length
of the muscle fiber. This means that the greater the stretch of the ventricular muscle (within limits), the more powerful the contraction is, which
in turn increases SV. Therefore, by increasing preload, you increase the second variable, contractility.
Otto Frank (1865–1944) was a German physiologist; among his many published works are detailed studies of this important heart relationship.
Ernest Starling (1866–1927) was an important English physiologist who also studied the heart. Although they worked largely independently,
their combined efforts and similar conclusions have been recognized in the name “Frank-Starling mechanism.”
Any sympathetic stimulation to the venous system will increase venous return to the heart, which contributes to ventricular filling, and EDV and
preload. While much of the ventricular filling occurs while both atria and ventricles are in diastole, the contraction of the atria, the atrial kick,
plays a crucial role by providing the last 20–30 percent of ventricular filling.

Contractility
It is virtually impossible to consider preload or ESV without including an early mention of the concept of contractility. Indeed, the two
parameters are intimately linked. Contractility refers to the force of the contraction of the heart muscle, which controls SV, and is the primary
parameter for impacting ESV. The more forceful the contraction is, the greater the SV and smaller the ESV are. Less forceful contractions result
in smaller SVs and larger ESVs. Factors that increase contractility are described as positive inotropic factors, and those that decrease
contractility are described as negative inotropic factors (ino- = “fiber;” -tropic = “turning toward”).
Not surprisingly, sympathetic stimulation is a positive inotrope, whereas parasympathetic stimulation is a negative inotrope. Sympathetic
stimulation triggers the release of NE at the neuromuscular junction from the cardiac nerves and also stimulates the adrenal cortex to secrete
epinephrine and NE. In addition to their stimulatory effects on HR, they also bind to both alpha and beta receptors on the cardiac muscle cell
membrane to increase metabolic rate and the force of contraction. This combination of actions has the net effect of increasing SV and leaving a
smaller residual ESV in the ventricles. In comparison, parasympathetic stimulation releases ACh at the neuromuscular junction from the vagus
nerve. The membrane hyperpolarizes and inhibits contraction to decrease the strength of contraction and SV, and to raise ESV. Since
parasympathetic fibers are more widespread in the atria than in the ventricles, the primary site of action is in the upper chambers.
Parasympathetic stimulation in the atria decreases the atrial kick and reduces EDV, which decreases ventricular stretch and preload, thereby
further limiting the force of ventricular contraction. Stronger parasympathetic stimulation also directly decreases the force of contraction of the
ventricles.
Several synthetic drugs, including dopamine and isoproterenol, have been developed that mimic the effects of epinephrine and NE by
stimulating the influx of calcium ions from the extracellular fluid. Higher concentrations of intracellular calcium ions increase the strength of
contraction. Excess calcium (hypercalcemia) also acts as a positive inotropic agent. The drug digitalis lowers HR and increases the strength of
the contraction, acting as a positive inotropic agent by blocking the sequestering of calcium ions into the sarcoplasmic reticulum. This leads to
higher intracellular calcium levels and greater strength of contraction. In addition to the catecholamines from the adrenal medulla, other
hormones also demonstrate positive inotropic effects. These include thyroid hormones and glucagon from the pancreas.
Negative inotropic agents include hypoxia, acidosis, hyperkalemia, and a variety of synthetic drugs. These include numerous beta blockers and
calcium channel blockers. Early beta blocker drugs include propranolol and pronethalol, and are credited with revolutionizing treatment of
cardiac patients experiencing angina pectoris. There is also a large class of dihydropyridine, phenylalkylamine, and benzothiazepine calcium
channel blockers that may be administered decreasing the strength of contraction and SV.

Afterload
Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system. Any
condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood. Damage to the valves,
such as stenosis, which makes them harder to open will also increase afterload. Any decrease in resistance decreases the afterload. Figure
4summarizes the major factors influencing SV, Figure 5 summarizes the major factors influencing CO, and Table 3 and Table 4 summarize
cardiac responses to increased and decreased blood flow and pressure in order to restore homeostasis.

Figure 4. Major Factors Influencing Stroke Volume. Multiple factors impact preload, afterload, and contractility, and are the major
considerations influencing SV.

Figure 5. Summary of Major Factors Influencing Cardiac Output. The primary factors influencing HR include autonomic innervation plus
endocrine control. Not shown are environmental factors, such as electrolytes, metabolic products, and temperature. The primary factors
controlling SV include preload, contractility, and afterload. Other factors such as electrolytes may be classified as either positive or negative
inotropic agents.
Cardiac Response to Decreasing Blood Flow and Pressure Due to Decreasing Cardiac Output (Table 3)

Baroreceptors (aorta, carotid arteries, venae Chemoreceptors (both central nervous system
cavae, and atria) and in proximity to baroreceptors)

Sensitive to Decreasing stretch Decreasing O2 and increasing CO2, H+, and lactic acid

Target Parasympathetic stimulation suppressed Sympathetic stimulation increased

Response of
Increasing heart rate and increasing stroke volume Increasing heart rate and increasing stroke volume
heart
 Cardiac Response to Decreasing Blood Flow and Pressure Due to Decreasing Cardiac Output (Table 3)

Baroreceptors (aorta, carotid arteries, venae Chemoreceptors (both central nervous system
cavae, and atria) and in proximity to baroreceptors)

Increasing blood flow and pressure due to increasing Increasing blood flow and pressure due to increasing
Overall effect
cardiac output; hemostasis restored cardiac output; hemostasis restored

Cardiac Response to Increasing Blood Flow and Pressure Due to Increasing Cardiac Output (Table 4)

Baroreceptors (aorta, carotid arteries, venae Chemoreceptors (both central nervous system
cavae, and atria) and in proximity to baroreceptors)

Sensitive to Increasing stretch Increasing O2 and decreasing CO2, H+, and lactic acid

Target Parasympathetic stimulation increased Sympathetic stimulation suppressed

Response of
Decreasing heart rate and decreasing stroke volume Decreasing heart rate and decreasing stroke volume
heart

Decreasing blood flow and pressure due to Decreasing blood flow and pressure due to decreasing
Overall effect
decreasing cardiac output; hemostasis restored cardiac output; hemostasis restored

GLOSSARY
afterload
force the ventricles must develop to effectively pump blood against the resistance in the vessels
autonomic tone
contractile state during resting cardiac activity produced by mild sympathetic and parasympathetic stimulation
atrial reflex
(also, called Bainbridge reflex) autonomic reflex that responds to stretch receptors in the atria that send impulses to the
cardioaccelerator area to increase HR when venous flow into the atria increases
Bainbridge reflex
(also, called atrial reflex) autonomic reflex that responds to stretch receptors in the atria that send impulses to the cardioaccelerator
area to increase HR when venous flow into the atria increases
baroreceptor reflex
autonomic reflex in which the cardiac centers monitor signals from the baroreceptor stretch receptors and regulate heart function
based on blood flow
cardiac output (CO)
amount of blood pumped by each ventricle during one minute; equals HR multiplied by SV
cardiac plexus
paired complex network of nerve fibers near the base of the heart that receive sympathetic and parasympathetic stimulations to
regulate HR
cardiac reflexes
series of autonomic reflexes that enable the cardiovascular centers to regulate heart function based upon sensory information from
a variety of visceral sensors
cardiac reserve
difference between maximum and resting CO
ejection fraction
portion of the blood that is pumped or ejected from the heart with each contraction; mathematically represented by SV divided by
EDV
filling time
duration of ventricular diastole during which filling occurs
Frank-Starling mechanism
relationship between ventricular stretch and contraction in which the force of heart contraction is directly proportional to the initial
length of the muscle fiber
heart rate (HR)
number of times the heart contracts (beats) per minute
negative inotropic factors
factors that negatively impact or lower heart contractility
positive inotropic factors
factors that positively impact or increase heart contractility
stroke volume (SV)
amount of blood pumped by each ventricle per contraction; also, the difference between EDV and ESV
target heart rate
range in which both the heart and lungs receive the maximum benefit from an aerobic workout

2. Eisenmenger syndrome
EISENMENGER SYNDROME
  Eisenmenger syndrome is the condition o severe pulmonary vascular obstruction that results rom chronic le t-to-right shunting through
a congenital cardiac de ect. The elevated pulmo- nary vascular resistance causes reversal o the original shunt (to the right-to-le t
direction)
 and systemic cyanosis.
The mechanism by which increased pulmonary f ow causes this condition is unknown.
 Histologically, the pulmonary arteriolar media hypertrophies and the intima proli erates, reducing the cross-sectional area o the
pulmonary vascular bed. Over time, the vessels become thrombosed, and the resistance o the pulmonary vasculature rises, causing the
origi- nal le t-to-right shunt to decrease. Eventually, i the resistance o the pulmonary circulation exceeds that o the systemic
vasculature, the direction o shunt f ow reverses.
 With reversal o the shunt to the right-to-le t direction, symptoms arise rom hypoxemia, including exertional dyspnea and atigue.
Reduced hemoglobin saturation stimulates the bone marrow to produce more red blood cells (erythrocytosis), which can lead to
hyperviscosity, symptoms o which include atigue, headaches, and stroke (caused by cerebrovascular occlu- sion). In arction or rupture
o the pulmonary vessels can result in hemoptysis.
 On examination, a patient with Eisenmenger syndrome appears cyanotic with digital club- bing. A prominent a wave in the jugular
venous pulsation ref ects elevated right-sided pres- sure during atrial contraction. A loud P 2 is common. The murmur o the inciting le
t-to-right shunt is usually absent, because the original pressure gradient across the lesion is negated by the elevated right-heart
pressures.
 Chest radiography in Eisenmenger syndrome is notable or proximal pulmonary artery dilatation with peripheral tapering. Calci cation
o the pulmonary vasculature may be seen. The ECG demonstrates right ventricular hypertrophy and right atrial enlargement.
Echocardiography with Doppler studies can usually identi y the underlying cardiac de ect and quantitate the pulmonary artery systolic
pressure.
 Treatment includes the avoidance o activities that can exacerbate the right-to-le t shunt. These include strenuous physical activity, high
altitude, and the use o peripheral vasodila- tor drugs. Pregnancy is especially dangerous; the rate o spontaneous abortion is 20% to
40%, and the incidence o maternal mortality is approximately 45%. Supportive measures or Eisenmenger syndrome include prompt
treatment o in ections, management o rhythm disturbances, and phlebotomy or patients with symptomatic erythrocytosis.
 Although there are no remedies that reverse the disease process in Eisenmenger syndrome, pulmonary vasodilator therapy can provide
symptomatic relie and improve the patient’s quality o li e. E ective agents include endothelin receptor antagonists, prostacyclin
analogs, and phosphodiesterase inhibitors (see Chapter 17). The only e ective long-term strategy or severely a ected patients is lung
or heart–lung transplantation. Fortunately, with the dramatic advances that have been made in the detection and early correction o
severe congenital heart de ects, Eisenmenger syndrome has become less common.

3. Heart sounds

4. Children Heart Failure

Congestive heart failure occurs when the heart can no longer meet the metabolic demands of the body at normal physiologic
venous pressures. Typically, the heart can respond to increased demands by means of 1 of the following:
 Increasing the heart rate, which is controlled by neural and humoral input
 Increasing the contractility of the ventricles, secondary to circulating catecholamines and autonomic input
 Augmenting the preload, medicated by constriction of the venous capacitance vessels and the renal preservation of
intravascular volume
As the demands on the heart outstrip the normal range of physiologic compensatory mechanisms, signs of congestive heart failure
occur. These signs include tachycardia; venous congestion; high catecholamine levels; and, ultimately, insufficient cardiac output
with poor perfusion and end-organ compromise. (See the image below.)
 Chest radiograph shows signs of congestive heart failure (CHF).
Systolic dysfunction

Diminished cardiac output is caused by a complex interaction of various factors. [2] Systolic dysfunction is characterized by
diminished ventricular contractility that results in an impaired ability to increase the stroke volume to meet systemic demands.
Factors such as anatomic stresses (eg, coarctation of the aorta) that contribute to an increased afterload (end-systolic wall stress),
as well as neurohormonal factors that increase systemic vascular resistance, also lead to systolic dysfunction.
Diastolic dysfunction
Diastolic dysfunction results from decreased ventricular compliance, necessitating an increase in venous pressure to maintain
adequate ventricular filling. Causes of primary diastolic dysfunction include an anatomic obstruction that prevents ventricular filling
(eg, pulmonary venous obstruction), a primary reduction in ventricular compliance (eg, cardiomyopathy, transplant rejection),
external constraints (eg, pericardial effusion), and poor hemodynamics after the Fontan procedure (eg, elevated pulmonary
vascular resistance).
Chronic heart failure
In chronic heart failure, myocardial cells die from energy starvation, from cytotoxic mechanisms leading to necrosis, or from the
acceleration of apoptosis or programmed cell death. Necrosis stimulates fibroblast proliferation, which results in the replacement of
myocardial cells with collagen. The loss of myocytes leads to cardiac dilation and an increased afterload and wall tension, which
results in further systolic dysfunction. In addition, the loss of mitochondrial mass leads to increased energy starvation.
Acute heart failure
During acute congestive heart failure, the sympathetic nervous system and renin-angiotensin system act to maintain blood flow and
pressure to the vital organs. Increased neurohormonal activity results in increased myocardial contractility, selective peripheral
vasoconstriction, salt and fluid retention, and blood pressure maintenance. As a chronic state of failure ensues, these same
mechanisms cause adverse effects.
The myocardial oxygen demand, which exceeds the supply, increases because of an increase in the heart rate, in contractility, and
in wall stress. Alterations in calcium homeostasis and changes in contractile proteins occur, resulting in a hypertrophic response of
the myocytes. Neurohormonal factors may lead to direct cardiotoxicity and necrosis.
Characteristic findings in children with heart failure
Many classes of disorders can result in increased cardiac demand or impaired cardiac function. Cardiac causes include
arrhythmias (tachycardia or bradycardia), structural heart disease, and myocardial dysfunction (systolic or diastolic).
Noncardiac causes of congestive heart failure include processes that increase the preload (volume overload), increase the
afterload (hypertension), reduce the oxygen-carrying capacity of the blood (anemia), or increase demand (sepsis). For example,
renal failure can result in congestive heart failure due to fluid retention and anemia. Renal failure may also occur following heart
transplantation as a result of long-term immunosuppression. [3]
Cardiac rhythm disorders may be caused by the following:
 Complete heart block
 Supraventricular tachycardia
 Ventricular tachycardia
 Sinus node dysfunction
Volume overload may be caused by the following:
 Structural heart disease (eg, ventricular septal defect, [4] patent ductus arteriosus, aortic or mitral valve regurgitation, complex
cardiac lesions)
 Anemia
 Sepsis
Pressure overload may be caused by the following:
 Structural heart disease (eg, aortic or pulmonary stenosis, aortic coarctation)
 Hypertension
Systolic ventricular dysfunction or failure may be caused by the following:
 Myocarditis
 Dilated cardiomyopathy
  Malnutrition
 Ischemia
Diastolic ventricular dysfunction or failure may be caused by the following:
 Hypertrophic cardiomyopathy
 Restrictive cardiomyopathy
 Pericarditis
 Cardiac tamponade (pericardial effusion)

Clinical Presentation
Thorough history taking and physical examination, including an assessment of the upper-extremity and lower-extremity blood
pressures, are crucial in the evaluation of an infant or child with congestive heart failure.
Regardless of the etiology, the first manifestation of congestive heart failure is usually tachycardia. An obvious exception to this
finding occurs in congestive heart failure due to a primary bradyarrhythmia or complete heart block.
As the severity of congestive heart failure increases, signs of venous congestion usually ensue. Left-sided heart failure is generally
associated with signs of pulmonary venous congestion, whereas right-sided heart failure is associated with signs of systemic
venous congestion. Marked failure of either ventricle, however, can affect the function of the other, leading to systemic and
pulmonary venous congestion.
Later stages of congestive heart failure are characterized by signs and symptoms of low cardiac output. Generally, congestive
heart failure with normal cardiac output is called compensated congestive heart failure, and congestive heart failure with
inadequate cardiac output is considered decompensated.
Signs of congestive heart failure vary with the age of the child. [5] Signs of pulmonary venous congestion in an infant generally
include tachypnea, respiratory distress (retractions), grunting, and difficulty with feeding. Often, children with congestive heart
failure have diaphoresis during feedings, which is possibly related to a catecholamine surge that occurs when they are challenged
with eating while in respiratory distress.
Right-sided venous congestion is characterized by hepatosplenomegaly and, less frequently, by edema or ascites. Jugular venous
distention is not a reliable indicator of systemic venous congestion in infants, because the jugular veins are difficult to observe. In
addition, the distance from the right atrium to the angle of the jaw may be no more than 8-10 cm, even when the individual is sitting
upright.
Uncompensated congestive heart failure in an infant primarily manifests as a failure to thrive. In severe cases, failure to thrive may
be followed by signs of renal and hepatic failure.
In older children, left-sided venous congestion causes tachypnea, respiratory distress, and wheezing (cardiac asthma). Right-sided
congestion may result in hepatosplenomegaly, jugular venous distention, edema, ascites, and/or pleural effusions.
Older children with uncompensated congestive heart failure may have fatigue or lower-than-usual energy levels. Patients may
complain of cool extremities, abdominal pain, nausea/vomiting, exercise intolerance, dizziness, or syncope.

TREATMENT
Pharmacologic Therapy
Preload reduction can be achieved with oral (PO) or intravenous (IV) diuretics (eg, furosemide, thiazides, metolazone). Venous
dilators (eg, nitroglycerin) can be administered, but their use is less common in pediatric practice. Contractility can be supported
with IV agents (eg, dopamine) or mixed agents (eg, dobutamine, inamrinone, milrinone). Digoxin appears to have some benefit in
congestive heart failure, but the exact mechanism is unclear. Ivabradine may be considered to lower heart rate in stable
symptomatic heart failure owing to dilated cardiomyopathy.
Afterload reduction is obtained orally through administration of angiotensin-converting enzyme (ACE) inhibitors or intravenously
through administration of other agents, such as hydralazine, nitroprusside, and alprostadil. Pharmaceutical agents used in the
treatment of congestive heart failure are summarized in the Table below.
Table. Pharmaceutical Agents Used in the Treatment of Congestive Heart Failure (Open Table in a new window)

Agent Pediatric Dose Comment

Preload Reduction

Furosemide 1 mg/kg/dose PO or IV May increase to qid

Hydrochlorothiazide 2 mg/kg/d PO divided bid May increase to qid

Used with loop diuretic, may increase to

Metolazone 0.2 mg/kg/dose PO
bid

Inotropic

Preterm infants: 0.005 mg/kg/d PO divided bid or

Digoxin 75% of this dose IV; age 10 y: 0.005 mg/kg/d PO ...
qd or 75% of this dose IV
 5-10 mcg/kg/min IV (usual dosage; maximal
Dopamine Gradually titrate upward to desired effect
dosage may be up to 28 mcg/kg/min)

Dobutamine 5-10 mcg/kg/min IV Gradually titrate upward to desired effect

Epinephrine 0.01-0.03 mcg/kg/min IV Not to exceed 0.1-0.3 mcg/kg/min

Typically used without loading dose,

Milrinone 0.3-1 mcg/kg/min IV especially in unstable patients
Load: 50 mcg/kg IV over 15 min

Afterload Reduction

Captopril 0.1-0.5 mg/kg/d PO divided q8h ...

Adults: 2.5-5 mg/day PO qd/bid initially;

0.1 mg/kg/d PO divided qd/bid, not to exceed 0.5 titrate slowly at 1- to 2-wk intervals; target
Enalapril
mg/kg/d dose is 10-20 mg PO bid; not to exceed 40
mg/day

Adults: Usual dosage is 10mg PO qd

Lisinopril Not established
(range, 2.5-10 mg)

Initial dose for hypertension is 0.1 mg/kg/day PO;

Losartan dosage for treatment of CHF is not established in Adults: 25-100 mg/d PO qd or divided bid
children

Nitroprusside 0.5-10 mcg/kg/min IV May need to monitor cyanide level

Nitroglycerin 0.1-0.5 mcg/kg/min IV Vasodilator

Initiate with 0.01 mcg/kg/min

Nesiritide 0.01-0.03 mcg/kg/min IV
May cause dose-related hypotension

Alprostadil* 0.03-0.1 mcg/kg/min IV ...

[7]
Beta-Blockade

Limited data suggest a therapeutic dosage range

of 0.2-0.4 mg/kg/dose PO bid; initiate with lower Adults: 12.5-25 mg PO bid
Carvedilol
dose and gradually increase dose q2-3wk to Initiate with 3.125 mg PO bid
therapeutic range

Metoprolol Not established Adults: 25-100 mg PO qd

Selective Aldosterone Antagonists

Adults: 12.5-50 mg PO qd; reduce dose to

Spironolactone 1-3.3 mg/kg/day PO in single or divided doses
25 mg qod if hyperkalemia occurs

Eplerenone Not established 25-50 mg PO qd

 I(f) Current Inhibitor

Initial >6 mo and < 40 kg: 0.05 mg/kg PO BID

Ivabradine Maximum: 0.2 mg/kg BID (6 mo-1 y); 0.3 mg/kg Lowers heart rate
BID (1 y or older)

*Prostaglandin E1 (PGE1).

Managing Acute Congestive Heart Failure in the Neonate or Infant

Acute presentation of the ill newborn or infant with congestive heart failure warrants immediate concern regarding potential sepsis
or ductal-dependent congenital heart disease. The evaluation and treatment of these patients are often best performed in the
neonatal or pediatric intensive care unit (ICU).
The initial management involves the usual assessment of the patient's airway, breathing, and circulation (ABCs); achieving IV
access; laboratory testing, including a blood culture; and empiric antibiotic therapy. Management of low cardiac output can be
initiated by using a dopamine infusion of 5-10 mcg/kg/min; acidosis can be corrected with the administration of fluid and/or
bicarbonate.
Calcium should be administered when hypocalcemia is documented. Because ductal-dependent structural heart disease is a
common cause of congestive heart failure in early infancy, echocardiography should be considered early in the evaluation if a
diagnosis is not immediately forthcoming.
Anatomic lesions that may appear early and that should be considered include the following:
 Coarctation or interruption of the aortic arch
 Total anomalous pulmonary venous return
 Hypoplastic left heart syndrome (or variants, including severe mitral valve stenosis and/or aortic valve stenosis or atresia)
 Truncus arteriosus
 Pulmonary atresia
 Transposition of the great arteries
Conditions to consider in young infants with a more protracted congestive heart failure course include those producing significant
left-to-right shunts, including large ventricular septal defects, aortopulmonary shunts, and arteriovenous malformations.
Prostaglandin
An alprostadil (PGE1) infusion is indicated when ductal-dependent cardiac lesions are diagnosed or when they cannot be ruled out
in a timely fashion. Absent femoral pulses or the inability to increase the systemic PaO2 to above 150mm Hg with a fraction of
inspired oxygen (FiO2) of 1 suggests a ductal-dependent lesion, and treatment with PGE1 is warranted.
PGE1 may theoretically aggravate the condition in some children with total anomalous pulmonary venous connection and
obstruction or in children with other etiologies of congestive heart failure, such as sepsis. Whenever possible, echocardiography
should be performed before PGE1 treatment is begun. On the other hand, when critical heart disease is present and
echocardiography is not immediately available, prostaglandin infusion can be lifesaving.
Nonstructural problems
Nonstructural cardiac problems that occur during this stage include tachyarrhythmias (usually supraventricular tachyarrhythmia
[SVT]) and complete heart block. Prompt pharmacologic or electrical cardioversion is warranted in any patient with a
tachyarrhythmia who presents with congestive heart failure. Primary cardiomyopathy or myopathic disease secondary to inborn
errors of metabolism should be considered in the absence of structural cardiac disease or arrhythmia when cardiac dysfunction is
present.
Managing Acute Congestive Heart Failure in the Older Child
Long-standing but unrecognized congestive heart failure may present acutely; similarly, an acute presentation may represent an
acute onset of acquired cardiac disease (myocarditis or arrhythmia). Management of acute decompensation involves treatment of
presenting symptoms and adjustment or initiation of long-term therapy.
In older children with acute congestive heart failure, admit to the ICU for diuresis with IV furosemide. For patients with significant
hypotension, IV dopamine (5-10 mcg/kg/min) or milrinone (0.3-1 mcg/kg/min) infusion is appropriate until stabilization is achieved.
Older children may require the placement of a central venous or pulmonary artery catheter to monitor venous pressure and cardiac
output during stabilization.
Nitrates (nitroprusside, nitroglycerin) or nesiritide may be useful in patients with elevated pulmonary capillary wedge pressure and
pulmonary congestion due to their venous dilating effects. Nesiritide carries the additional theoretical benefits of reversing
deleterious neurohumoral responses and increasing natriuresis. Small studies have been conducted to measure hemodynamic
effects of nesiritide in children with dilated cardiomyopathy. [8, 9] However, nesiritide has demonstrated no mortality advantage
compared with nitroglycerin for acute decompensated heart failure in a large adult trial. [10]
Managing Chronic or Stable Congestive Heart Failure
If the underlying cause of the congestive heart failure cannot be immediately corrected in a patient who is hemodynamically stable,
outpatient management can be initiated by using several agents. Afterload reduction using an ACE inhibitor is indicated in the
presence of left ventricular (LV) dysfunction, regardless of symptoms.
Afterload reduction is indicated in patients who have large left-to-right shunts at the ventricular or arterial level (ventricular septal
defect or patent ductus arteriosus), left-sided regurgitant lesions (aortic insufficiency or mitral regurgitation), or poor systolic
function (myocarditis or dilated cardiomyopathy). ACE inhibitors are the medications of choice. Alternatively, an angiotensin
receptor blocker (ARB), such as losartan, may be used in patients in whom ACE adverse effects (particularly cough) may be
unacceptable. [11]
In addition to afterload reduction (ACE inhibitor), low-dose furosemide (1 mg/kg/dose PO bid) may be initiated, with or without the
addition of another agent for inotropic effect (digoxin), or beta-blockade (carvedilol) to treat mild symptoms of congestive heart
failure. [12] The dose of digoxin (0.005-0.010 mg/kg/day PO divided twice daily, not to exceed 0.125-0.250 mg PO qd) is almost
never increased, either for effect or according to digoxin levels, which are notoriously unreliable. However, the dose may be
decreased in the presence of signs of toxicity. The suspicion of digoxin toxicity should increase if an infant is uninterested in
feedings, gags, or vomits frequently. These symptoms are typically due to an overdose or renal failure.
For more severe congestive heart failure, diuretic therapy with oral furosemide may be increased to 2 mg/kg/dose orally 3 times
daily or a second agent, such as hydrochlorothiazide or metolazone, can be added. To be most effective, hydrochlorothiazide and
metolazone are best administered simultaneously with furosemide to achieve their synergistic effect.
Aldosterone antagonists

Aldosterone antagonists are potassium-sparing diuretics. Spironolactone or eplerinone have class I indication for use in heart
failure in adults, including any patient with a left ventricular ejection fraction (LVEF) of less than 40% in the presence of even
minimal symptoms. [13, 14, 15] Their mechanism of action in heart failure is unknown. Pediatric studies have not been performed, but
these agents have been used in children for a variety of indications, including diuretic-induced hypokalemia. The usual dosage for
children is spironolactone 1-3.3 mg/kg/day in single or divided doses.
Potassium
For patients taking more than 1 mg/kg of oral furosemide twice daily without ACE inhibitors, spironolactone should be added for its
potassium-sparing effect and theoretical beneficial effects on cardiac remodeling. Adult studies have suggested that it prolongs
survival in chronic heart failure. [16] Alternatively, serum potassium levels may be monitored, and appropriate supplementation
should be provided. Supplemental potassium chloride may be required when high doses of diuretics are used, but most children
are extremely averse to the taste of most preparations. Alternatively, aldosterone antagonists may be administered to treat chronic
diuretic-induced hypokalemia.
Because ACE inhibitors and aldosterone antagonists cause potassium retention, supplemental potassium should be avoided
except in the presence of documented hypokalemia in patients taking these medications.
Sodium
Hyponatremia often accompanies congestive heart failure and is caused by water retention in response to vasopressin (antidiuretic
hormone), which is produced as a result of renin-angiotensin activation but may be exacerbated by the use of diuretics and by salt
wasting by the kidney.
Sodium supplementation is almost never indicated in infants or children with congestive heart failure except in emergency
situations. Severe hyponatremia is generally best managed by reducing the dose of diuretics or by restricting fluid intake, although
the latter has little use in small children. In any child taking more than 2 mg/kg/d of furosemide, electrolyte levels should be checked
every few months, as they should be in any child taking furosemide in conjunction with other diuretics or ACE inhibitors.
Beta blockers
Experience with beta-blocker therapy in pediatric patients has increased. The selective beta1-blocker metoprolol and the
nonselective beta1-blocker and beta2-blocker carvedilol, used primarily in adults, have generally shown encouraging results in
select patients with cardiomyopathy and mild or moderate chronic congestive heart failure. Adults using these beta blockers
(carvedilol) have demonstrated an increased stroke volume and stroke work index during exercise, along with a decreased heart
rate and LV chamber size. [17, 18]
In addition, carvedilol has been shown to decrease pulmonary artery mean and wedge pressures, decrease cardiac norepinephrine
levels, and increase peripheral vasodilation by means of alpha1 blockade. For these reasons, in part, use of carvedilol has
increased, particularly in cardiomyopathies.
However, a double-blind, randomized trial (carvedilol vs placebo) in pediatric patients with mild to moderate congestive heart failure
failed to demonstrate a benefit in reduction of symptoms or mortality. The power of the study was affected by an unexpectedly high
rate of improvement among all patients, including those who received placebo. [19] Thus, the exact indications and benefits of
carvedilol therapy in children with heart failure remain somewhat unclear. [7]
I(f) current inhibitor
Ivabradine was approved by the FDA in April 2019 for children aged 6 months or older with stable symptomatic heart failure caused
by dilated cardiomyopathy who are in sinus rhythm with an elevated heart rate. Ivabradine blocks the hyperpolarization-activated
cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker I(f) ‘funny’ current, which regulates heart rate.
The primary endpoint or 20% or greater reduction of heart rate from baseline without producing bradycardia or symptoms was
reached by 51 of 73 children taking ivabradine (70%) compared with 5 of 41 taking placebo (12%) at varying doses (odds ratio:
17.24; p < 0.0001). Between baseline and 12 months, there was a greater increase in left ventricular ejection fraction in patients
taking ivabradine than placebo (13.5% vs. 6.9%; p = 0.024). New York Heart Association functional class or Ross class improved
more with ivabradine at 12 months than placebo (38% vs. 25%; p = 0.24). [25]
Anemia

Often overlooked in the management of chronic congestive heart failure is the role of the oxygen-carrying capacity of the blood.
Anemia aggravates congestive heart failure by increasing the demands for cardiac output, and careful attention to iron stores or the
administration of red cell transfusions often results in a significant improvement.
Nutrition

Nutrition is crucial in the management of chronic congestive heart failure. Particularly during infancy, congestive heart failure
increases the metabolic demands while making feeding itself more difficult. Enhanced caloric content feedings and, in some cases,
nasogastric or gastrostomy feedings may be necessary to maintain the patient's growth.
Growth

The success of medical therapy of congestive heart failure in infants and small children is judged according to the child's growth.
The failure to gain weight in the setting of marked congestive heart failure signifies that the current regimen is not sufficient. A
failure to thrive is an indication for increased medical management or, when the option is available, surgical repair of structural
heart disease.

Device-Based Therapies : Cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) has emerged as a useful therapy in the treatment of chronic congestive heart failure. CRT
involves the use of biventricular pacemakers to improve ventricular function by electrically adjusting the timing of right and left
ventricular contraction to optimize wall motion and increase filling time. In addition to increasing stroke volume, CRT may allow for
reverse remodeling to delay disease progression. Clinical trials in adults with moderate to severe heart failure have demonstrated
beneficial effects of CRT use, including reduction of symptoms, increased exercise capacity, and decreased morbidity and
mortality.[20]
In pediatric practice, resynchronization therapy has been limited; the initial studies described the results for this modality instituted
in children with chronic heart failure who required pacemakers for treatment of rhythm disorders. Use of this therapy is more difficult
to institute in children, whose small size requires the use of surgically placed epicardial pacemakers rather than percutaneously
placed pacemakers. As more registry and retrospective data have accumulated, use of this therapy has increased, and indications
based on echocardiographic and electrocardiographic parameters continue to be refined. [21, 22]
Mechanical support
Mechanical support may be used in the treatment of acute heart failure (ie, myocarditis or postcardiotomy syndrome) or in chronic
heart failure as a bridge to recovery or to a heart transplant. The choice of support therapy depends on the expected duration of
use.
Extracorporeal membrane oxygenation (ECMO) therapy may be quickly initiated in unstable patients. Generally, its duration of use
is limited to days or weeks because of complications related to infection or anticoagulation. ECMO is used to provide acute
temporary support as a bridge to recovery or transplantation.
In a study of ECMO use in 108 patients (73 adults and 35 children), most of whom were suffering from postcardiotomy cardiac low
output, Beiras-Fernandez et al found that pediatric patients who had undergone congenital heart surgery were among the patients
who demonstrated the best results from ECMO. [23]
Ventricular assist devices (VADs; eg, Berlin Heart, EXCOR Pediatric System, Thoratec VAD) may be used to provide long-term
ventricular support. The EXCOR Pediatric System is the first pulsatile mechanical circulatory support device specifically designed
for children and was approved by the FDA in December 2011. The device consists of 1 or 2 external pneumatic blood pumps to
support the left ventricle alone or both the left and right ventricles. EXCOR is available in graduated sizes to fit children from
newborns to adolescents. [24] Also see FDA approves mechanical cardiac assist device for children with heart failure. Other devices,
such as Thoratec HeartMate II, have not received approval for pediatric use but have been used in selected cases for appropriately
sized patients. Currently, VADs are not approved forpermanent(destination) therapy in pediatric patients and should be considered
only as a bridge to transplantation in appropriate candidates. [12]