2. Objectives
• Introduction
• Summary of the Heart
» Embryology
» Anatomy
» Physiology
» Histology
• Cardiomyopathy
• Myocarditis
• Comparison of Cardiomyopathy and
Myocarditis
3. Introduction
• Cardiomyopathy is a group of diseases
that affect the heart muscle
• Myocarditis is an inflammation of the
myocardium, the middle layer of the heart
wall.
5. The Heart
The heart is a muscular organ about the size of
a fist, located between your lungs in the middle of
your chest, behind and slightly to the left of your
breastbone (sternum). Its between the 2nd
to 5th
/ 6th
rib anteriorly and between the 5th
to 8th
thoracic
vertebrae posteriorly, in an area called the
Mediastinum. The apex (lowest point) lies on the
diaphragm.
6. Embryology of the Heart
The heart is the first organ to form within the embryo
and this complex developmental process begins during the
fourth week.
At the beginning of 4th week of development,
heart is a continuous and valve-less linear tube that
resembles a chicken hung upside-down. It consists of 5
embryonic dilatation, that are destined to be the inflow and
outflow tract and compartments of the hear without septum
and valves.
8. Embryology of the Heart
The heart derives from splanchnopleuric mesenchyme in
the neural plate which forms the cardiogenic region. Two
endocardial tubes form here that fuse to form a primitive
heart tube known as the tubular heart. Between the third
and fourth week, the heart tube lengthens, and begins to
fold to form an S-shape within the pericardium. This places
the chambers and major vessels into the correct alignment
for the developed heart. Further development will include
the septa and valves formation and remodelling of the heart
chambers. By the end of the fifth week the septa are
complete and the heart valves are completed by the ninth
week.
10. Before the fifth week, there is an opening in the
fetal heart known as the foramen ovale. The
foramen ovale allowed blood in the fetal heart to
pass directly from the right atrium to the left atrium,
allowing some blood to bypass the lungs. Within
seconds after birth, a flap of tissue known as
the septum primum that previously acted as a
valve closes the foramen ovale and establishes
the typical cardiac circulation pattern. A depression
in the surface of the right atrium remains where the
foramen ovale once walls, called the fossa ovalis
Embryology of the Heart
12. The embryonic heart begins beating at around 22 days
after conception (5 weeks after the last normal menstrual
period, LMP). It starts to beat at a rate near to the mother's
which is about 75–80 beats per minute (bpm). The
embryonic heart rate then accelerates and reaches a peak
rate of 165–185 bpm early in the early 7th week (early 9th
week after the LMP). After 9 weeks (start of the fetal stage)
it starts to decelerate, slowing to around 145 (±25) bpm at
birth. There is no difference in female and male heart rates
before birth.
Embryology of the Heart
13. Anatomy of the Heart
The heart weighs between 7 and 15 ounces (200 to 425 grams)
and is a little larger than the size of your fist. By the end of a long life, a
person's heart may have beat (expanded and contracted) more than
3.5 billion times. In fact, each day, the average heart beats 100,000
times, pumping about 2,000 gallons (7,571 liters) of blood
our heart is located between your lungs in the middle of your chest,
behind and slightly to the left of your breastbone (sternum). A double-
layered membrane called the pericardium surrounds your heart like a
sac. The outer layer of the pericardium surrounds the roots of your
heart's major blood vessels and is attached by ligaments to your spinal
column, diaphragm, and other parts of your body. The inner layer of the
pericardium is attached to the heart muscle. A coating of fluid
separates the two layers of membrane, letting the heart move as it
beats.
14. The heart has 4 chambers. The upper chambers are
called the left and right atria, and the lower chambers are
called the left and right ventricles. A wall of muscle called
the septum separates the left and right atria and the left
and right ventricles. The left ventricle is the largest and
strongest chamber in your heart. The left ventricle's
chamber walls are only about a half-inch thick, but they
have enough force to push blood through the aortic valve
and into the body.
Anatomy of the Heart
16. Figure shows; A magnetic resonance image of mid-thorax showing the heart and all four
chambers and septum
Anatomy of the Heart
17. Four valves regulate blood flow through your heart:
•The tricuspid valve or right atrioventricular valve, is on the right dorsal side of
the mammalian heart, between the right atrium and the right ventricle. It
regulates blood flow between the right atrium and right ventricle.
•The pulmonary valve is located between the right ventricle and the pulmonary
artery and controls blood flow from the right ventricle into the pulmonary arteries,
which carry blood to your lungs to pick up oxygen.
•The mitral valve or bicuspid valve is situated between the left atrium and the left
ventricle. lets oxygen-rich blood from your lungs pass from the left atrium into
the left ventricle.
•The aortic valve is located between the right ventricle and the pulmonary artery
and opens the way for oxygen-rich blood to pass from the left ventricle into the
aorta, the body's largest artery.
Anatomy of the Heart
19. Layers of the heart:
• Pericardium
The heart sits within a fluid-filled cavity called the pericardial cavity. The
walls and lining of the pericardial cavity are a special membrane known
as the pericardium. Pericardium is a type of serous membrane that
produces serous fluid to lubricate the heart and prevent friction
between the ever beating heart and its surrounding organs. Besides
lubrication, the pericardium serves to hold the heart in position and
maintain a hollow space for the heart to expand into when it is full. The
pericardium has 2 layers—a visceral layer that covers the outside of
the heart and a parietal layer that forms a sac around the outside of the
pericardial cavity.
Anatomy of the Heart
20. Anatomy of the Heart
Structure of the Heart Wall
The heart wall is made of 3 layers: epicardium, myocardium and
endocardium.
•Epicardium. The epicardium is the outermost layer of the heart wall and is
just another name for the visceral layer of the pericardium. Thus, the
epicardium is a thin layer of serous membrane that helps to lubricate and
protect the outside of the heart. Below the epicardium is the second, thicker
layer of the heart wall: the myocardium.
•Myocardium. The myocardium is the muscular middle layer of the heart
wall that contains the cardiac muscle tissue. Myocardium makes up the
majority of the thickness and mass of the heart wall and is the part of the
heart responsible for pumping blood. Below the myocardium is the thin
endocardium layer.
21. • Endocardium. Endocardium is the simple squamous endothelium
layer that lines the inside of the heart. The endocardium is very
smooth and is responsible for keeping blood from sticking to the
inside of the heart and forming potentially deadly blood clots.
The thickness of the heart wall varies in different parts of the
heart. The atria of the heart have a very thin myocardium because
they do not need to pump blood very far—only to the nearby
ventricles. The ventricles, on the other hand, have a very thick
myocardium to pump blood to the lungs or throughout the entire
body. The right side of the heart has less myocardium in its walls
than the left side because the left side has to pump blood through
the entire body while the right side only has to pump to the lungs.
Anatomy of the Heart
23. The heart needs its own reliable blood supply in order to keep
beating- the coronary circulation. There are two main coronary arteries,
the left and right coronary arteries, and these branch further to form
several major branches (see image). The coronary arteries lie in
grooves (sulci) running over the surface of the myocardium, covered
over by the epicardium, and have many branches which terminate in
arterioles supplying the vast capillary network of the myocardium. Even
though these vessels have multiple anastomoses, significant
obstruction to one or other of the main branches will lead to ischaemia
in the area supplied by that branch.
Anatomy of the Heart
25. PHYSIOLOGY OF THE HEART
The heart is the pump responsible for
maintaining adequate circulation of oxygenated
blood around the vascular network of the body. It
is a four-chamber pump, with the right side
receiving deoxygenated blood from the body at low
presure and pumping it to the lungs (the
pulmonary circulation) and the left side receiving
oxygenated blood from the lungs and pumping it at
high pressure around the body (the systemic
circulation).
26. The myocardium (cardiac muscle) is a specialised
form of muscle, consisting of individual cells joined by
electrical connections. The contraction of each cell is
produced by a rise in intracellular calcium concentration
leading to spontaneous depolarisation, and as each cell is
electrically connected to its neighbour, contraction of one
cell leads to a wave of depolarisation and contraction
across the myocardium. This depolarisation and
contraction of the heart is controlled by a specialised group
of cells localised in the sino-atrial node in the right
atrium- the pacemaker cells.
PHYSIOLOGY OF THE HEART
27. PHYSIOLOGY OF THE HEART
• These cells generate a rhythmical depolarisation, which then
spreads out over the atria to the atrio-ventricular node.
• The atria then contract, pushing blood into the ventricles.
• The electrical conduction passes via the Atrio-ventricular
node to the bundle of His, which divides into right and left
branches and then spreads out from the base of the
ventricles across the myocardium.
• This leads to a 'bottom-up' contraction of the ventricles,
forcing blood up and out into the pulmonary artery (right) and
aorta (left).
• The atria then re-fill as the myocardium relaxes.
28. Histology of the Heart
• The heart is composed of cardiac muscle, specialised conductive tissue, valves,
blood vessels and connective tissue.
• Cardiac muscle, the myocardium, consists of cross-striated muscle cells,
cardiomyocytes, with one centrally placed nucleus.
• Nuclei are oval, rather pale and located centrally in the muscle cell which is 10 - 15
µm wide.
• Cardiac muscle cells excitation is mediated by rythmically active modified cardiac
muscle cells.
• Cardiac muscle is innervated by the autonomic nervous system (involuntary), which
adjusts the force generated by the muscle cells and the frequency of the heart beat.
• Cardiac muscle cells often branch at acute angles and are connected to each other
by specialisations of the cell membrane in the region of the intercalated discs.
– Intercalated discs invariably occur at the ends of cardiac muscle cells in a region
corresponding to the Z-line of the myofibrils.
• Cardiac muscle does not contain cells equivalent to the satellite cells of skeletal
muscle
29. Histology of the Heart
•Image of primate heart stained with
Alizarin blue.Red Blood Cells (orange cells)
Cardiac Muscle Cells (blue)
•Cardiac muscle cells are cut longitudinally.
•At high magnification see both striations
and the large nuclei of the cardiac muscle
cells.
•Follow the course of individual cardiac
muscle cells and note fine, dark blue lines
which seem to cross (traverse) the fibres.
•Intercalated Discs that connect the
individual muscle cells and permit the
conduction of electrical impulses between
the cells.
• seen in longitudinal sections.
31. Endocardium
•Inner layer of the heart (lines the atria and ventricles and
covers the heart valves) and contains blood vessels.
•Has 3 sublayers:
– Endothelium - innermost portion a simple squamous epithelium.
– Smooth Muscle and Connective Tissue - middle layer of the
endocardium is mix of connective tissue and smooth muscle.
– Subendocardial Layer - outer layer of the endocardium is loose
connective tissue joining the endocardium and myocardium.
•equivalent to tunica intima.
Histology of the Heart
32. Myocardium
•Middle layer of the heart, thickest layer contains
cardiomyocytes, blood vessels.
– contains cardiac muscle fibres and loose endomysial
connective tissue containing many capillaries.
•Muscular layer.
•equivalent to tunica media
Histology of the Heart
33. Epicardium
•Outer layer of the heart, contains blood vessels
and lymphatics.
– Fibro-elastic connective tissue, blood vessels,
lymphatics and adipose tissue.
•Visceral layer of pericardium rather thin.
•equivalent to tunica adventitia.
Histology of the Heart
35. Cardiomyopathy
The term cardiomyopathy (literally, heart muscle disease)
is used to describe heart disease resulting from a primary
abnormality in the myocardium.Although chronic myocardial
dysfunction due to ischemia should be excluded from the
cardiomyopathy rubric, the term ischemic cardiomyopathy
has gained some popularity among clinicians to describe
CHF caused by CAD (as discussed in the section "Chronic
Ischemic Heart Disease").
36. Etiology
Often, the cause of the cardiomyopathy is unknown. In
some people, however, doctors are able to identify some
contributing factors. Possible causes of cardiomyopathy
include:
•Genetic conditions
•Long-term high blood pressure
•Heart tissue damage from a previous heart attack
•Chronic rapid heart rate
•Heart valve problems
•Metabolic disorders, such as obesity, thyroid disease or
diabetes
37. Etiology
• Nutritional deficiencies of essential vitamins or minerals, such as
thiamin (vitamin B-1)
• Pregnancy complications
• Drinking too much alcohol over many years
• Use of cocaine, amphetamines or anabolic steroids
• Use of some chemotherapy drugs and radiation to treat cancer
• Certain infections, which may injure the heart and trigger
cardiomyopathy
• Iron build-up in your heart muscle (hemochromatosis)
• A condition that causes inflammation and can cause lumps of cells
to grow in the heart and other organs (sarcoidosis)
• A disorder that causes the build-up of abnormal proteins
(amyloidosis)
• Connective tissue disorders
38. Types of Cardiomyopathy
Cardiomyopathies can be classified according to a
variety of criteria, including the underlying genetic basis
of dysfunction; indeed, a number of the arrhythmia inducing
Channel opathies that are included in some classifications
of cardiomyopathy were alluded to earlier. For
purposes of general diagnosis and therapy, however, three
time-honored clinical, functional, and pathologic patterns
are recognized:
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
40. Types of Cardiomyopathy
Figure shows: The three major forms of cardiomyopathy. Dilated
cardiomyopathy
leads primarily to systolic dysfunction, whereas restrictive and
hypertrophic cardiomyopathies result in diastolic dysfunction. Note the
changes in atrial and/or ventricular dilation and in ventricular wall
thickness. Ao, aorta; LA, left atrium; LV, left ventricle.
41. Another rare form of cardiomyopathy is left ventricular
non-compaction; it is a congenital disorder characterized by
a distinctive “spongy” appearance of the ventricles,
associated with CHF and arrhythmias.
Among these three categories, the dilated form is most
common (90% of cases), and the restrictive is least
prevalent. Within the hemodynamic patterns of myocardial
dysfunction, there is a spectrum of clinical severity, and
overlap of clinical features often occurs between groups.
Moreover, each of these patterns can be either idiopathic
or due to a specific identifiable cause or secondary to
primary extra-myocardial disease.
Types of Cardiomyopathy
42. • Dilated Cardiomyopathy:
The term dilated cardiomyopathy (DCM) is applied to a form of
cardiomyopathy characterized by progressive cardiac dilation and
contractile (systolic) dysfunction, usually with concomitant hypertrophy. It is
sometimes called congestive cardiomyopathy. Although it is recognized that
approximately 25% to 35% of individuals with DCM have a familial (genetic)
form, DCM can result from a number of acquired myocardial insults that
ultimately yield a similar clinico-pathologic pattern. These include toxicities
(including chronic alcoholism, a history of which can be elicited in 10% to
20% of patients), myocarditis (an inflammatory disorder that precedes the
development of cardiomyopathy in at least some cases, as documented by
endo-myocardial biopsy), and pregnancy-associated nutritional deficiency or
immunologic reaction. In some patients, the cause of DCM is unknown;
such cases are appropriately designated as idiopathic dilated
cardiomyopathy.
Types of Cardiomyopathy
43. Pathogenesis:
By the time it is diagnosed, DCM has frequently already progressed to
end-stage disease; the heart is dilated and poorly contractile, and at
autopsy or cardiac transplant, fails to reveal any specific pathologic
features. Nevertheless, genetic and epidemiologic studies suggest
that at least five general pathways can lead to end-stage DCM :
Genetic causes. DCM has a hereditary basis in 20% to
50% of cases and over 40 genes are known to be mutated in this form
of cardiomyopathy; autosomal dominant inheritance is the
predominant pattern, most commonly involving mutations in
encoding cytoskeletal proteins, or proteins that link the sarcomere to
the cytoskeleton (e.g.,
α-cardiac actin).
Continuation
44. Continuation
X-linked DCM is most frequently associated with dystrophin gene
mutations affecting the cell membrane protein that physically couples
the intracellular cytoskeleton to the ECM; (different types of dystrophin
mutations also underlie Duchenne and Becker muscular dystrophies.
Uncommon forms of DCM are caused by mutations of genes in the
mitochondrial genome that encode proteins involved in oxidative
phosphorylation or fatty acid β-oxidation, presumably leading to
defective ATP generation. Other cytoskeletal proteins that are
affected in genetic forms of DCM include desmin (the principal
intermediate filament protein in cardiac myocytes), and the nuclear
lamins A and C. Since contractile myocytes and conduction fibers
share a common developmental pathway, congenital conduction
abnormalities also can be a feature of inherited forms of DCM.
45. Continuation
• Infection. The nucleic acid “footprints” of coxsackievirus B and
other enteroviruses can occasionally be detected in the myocardium
from late-stage DCM patients. Moreover, sequential endomyocardial
biopsies have documented instances in which infectious myocarditis
progressed to DCM. Consequently, many cases of DCM are
attributed to viral infections (discussed later), even though
inflammation is absent from the end-stage heart. Simply finding viral
transcripts or demonstrating elevated antiviral antibody titers may be
sufficient to invoke a myocarditis that was “missed” in its early
stages.
46. Continuation
• Alcohol or other toxic exposure. Alcohol abuse is
strongly associated with the development of DCM. Alcohol and its
metabolites (especially acetaldehyde) have a direct toxic effect on
myocardium. Moreover, chronic alcoholism can be associated with
thiamine deficiency, introducing an element of beriberi heart
disease.
47. Continuation
• Morphology
In DCM, the heart is usually heavy, often weighing two to three
times normal, and large and flabby, with dilation of all chambers (seen in
figure below ). Nevertheless, because of the wall thinning that
accompanies dilation, the ventricular thickness may be less than, equal to,
or greater than normal. Mural thrombi are common and may be a source
of thrombo-emboli. There are no primary valvular alterations, and mitral or
tricuspid regurgitation, when present, results from left ventricular chamber
dilation (functional regurgitation). The coronary arteries are usually free of
significant narrowing, but any coronary artery obstructions present are
insufficient to explain the degree of cardiac dysfunction.
48. Continuation
The characteristic histologic abnormalities in DCM are
nonspecific, and do not typically point to a specific etiologic
entity. An exception is DCM secondary to iron overload, in which
marked accumulation of intra-myocardial hemosiderin is demonstrable
by staining with Prussian blue.
In general, the severity of morphologic changes in DCM does not
necessarily reflect either the degree of dysfunction or the prognosis.
Most myocytes exhibit hypertrophy with enlarged nuclei, but many are
attenuated, stretched, and irregular. There is also variable interstitial
and endocardial fibrosis, with scattered areas of replacement fibrosis;
the latter mark previous myocyte ischemic necrosis caused by
hypoperfusion.
50. Continuation
Figure shows: The nonspecific
histologic picture in typical DCM,
with myocyte hypertrophy and
interstitial fibrosis (collagen is blue
in this Masson trichrome–stained
preparation).
51. Continuation
Hypertrophic cardiomyopathy
(HCM) is characterized by myocardial hypertrophy,
defective diastolic filling, and—in a third of cases—ventricular outflow
obstruction. The heart is thick-walled, heavy, and hypercontractile, in
striking contrast with the flabby, poorly contractile heart in DCM.
Systolic function usually is preserved in HCM, but the myocardium
does not relax and therefore exhibits primary diastolic dysfunction.
HCM needs to be distinguished clinically from disorders causing
ventricular stiffness (e.g., amyloid deposition) and ventricular
hypertrophy (e.g., aortic stenosis and hypertension).
52. Continuation
PATHOGENESIS
Most cases of HCM are caused by missense mutations in one of several genes
encoding proteins that form the contractile apparatus. In most cases, the
pattern of transmission is autosomal dominant, with variable expression.
Although more than 400 causative mutations in nine different genes have
been identified, HCM is fundamentally a disorder of sarcomeric proteins.
Of these, β-myosin heavy chain is most frequently affected, followed by
myosin-binding protein C and troponin T. Mutations in these three genes
account for 70% to 80% of all cases of HCM. The diverse mutations underlying
HCM have one unifying feature: they all affect sarcomeric proteins and increase
myofilament activation. This results in myocyte hypercontractility
with concomitant increase in energy use and net negative energy balance.
Some of the genes mutated in HCM are also mutated in DCM (e.g., beta-
myosin) but in DCM the (allelic) mutations depress motor function as opposed
to gain of function in HCM.
53. Continuation
MORPHOLOGY
HCM is marked by massive myocardial hypertrophy without ventricular
dilation. Classically, there is disproportionate thickening of the
ventricular septum relative to the left ventricle free wall (so-called
asymmetric septal hypertrophy); nevertheless, in about 10% of
cases of HCM, concentric hypertrophy is seen. On longitudinal
sectioning, the ventricular cavity loses its usual round-to-ovoid shape
and is compressed into a “banana-like” configuration. An endocardial
plaque in the left ventricular outflow tract and thickening of the anterior
mitral leaflet reflect contact of the anterior mitral leaflet with the septum
during ventricular systole; these changes correlate with functional left
ventricular outflow tract obstruction. The characteristic histologic
features in HCM are marked myocyte hypertrophy, haphazard
myocyte (and myofiber) disarray, and interstitial fibrosis.
54. Continuation
Clinical Features
Although HCM can present at any age it typically manifests
during the post pubertal growth spurt. The clinical symptoms can be
best understood in the context of the functional abnormalities. It is
characterized by a massively hypertrophied left ventricle that
paradoxically provides a markedly reduced stroke volume. This
condition occurs as a consequence of impaired diastolic filling and
overall smaller
55. Continuation
Figure shows: Hypertrophic cardiomyopathy with asymmetric septal hypertrophy. A,
The septal muscle bulges into the left ventricular outflow tract, giving rise to a
“banana-shaped” ventricular lumen, and the left atrium is enlarged. The anterior
mitral leaflet has been moved away from the septum to reveal a fibrous endocardial
plaque (arrow) (see text). B, Histologic appearance demonstrating disarray, extreme
hypertrophy, and characteristic branching of myocytes, as well as interstitial
fibrosis.
A B
56. Continuation
Restrictive Cardiomyopathy
Restrictive cardiomyopathy is characterized by a primary
decrease in ventricular compliance, resulting in impaired ventricular
filling during diastole (simply put, the wall is stiffer). Because the
contractile (systolic) function of the left ventricle usually is unaffected,
the functional state can be confused with constrictive pericarditis or
HCM. Restrictive cardiomyopathy can be idiopathic or associated with
systemic diseases that also happen to affect the myocardium, for
example radiation fibrosis, amyloidosis, sarcoidosis, or products of
inborn errors of metabolism.
58. Continuation
MORPHOLOGY
The ventricles are of approximately normal size or only
slightly enlarged, the cavities are not dilated, and the myocardium
is firm. Biatrial dilation commonly is due to poor ventricular
filling and pressure overloads. Microscopic examination
reveals variable degrees of interstitial fibrosis. Although gross
morphologic findings are similar for restrictive cardiomyopathy
of disparate causes, endomyocardial biopsy often can
reveal a specific etiologic disorder.
59. Continuation
Three forms of restrictive cardiomyopathy merit brief mention:
Amyloidosis is caused by the deposition of extracellular
proteins with the predilection for forming insoluble β-pleated sheets .
Cardiac amyloidosis can occur with systemic amyloidosis or can be
restricted to the heart, particularly in the case of senile cardiac
amyloidosis. In the latter instance, deposition of normal (or
mutant) forms of transthyretin (a liver-synthesized circulating
protein that transports thyroxine and retinol) in the hearts of elderly
patients results in a restrictive cardiomyopathy. Four percent of African
Americans carry a specific mutation of transthyretin that is responsible
for a four-fold increased risk of isolated cardiac amyloidosis
in that population.
60. Continuation
Endomyocardial fibrosis is principally a disease of children
and young adults in Africa and other tropical areas; it is characterized
by dense diffuse fibrosis of the ventricular endocardium and
subendocardium, often involving the tricuspid and mitral valves. The
fibrous tissue markedly diminishes the volume and compliance of
affected chambers, resulting in a restrictive physiology.
Endomyocardial
fibrosis has been linked to nutritional deficiencies and/or inflammation
related to helminthic infections (e.g., hypereosinophilia); worldwide,
it is the most common form of restrictive cardiomyopathy.
61. Continuation
Loeffler endomyocarditis also exhibits endocardial fibrosis,
typically associated with formation of large mural thrombi, but
without geographic predilection. Histologic examination typically
shows peripheral hypereosinophilia and eosinophilic tissue
infiltrates; release of eosinophil granule contents, especially major
basic protein, probably engenders endo- and myocardial necrosis,
followed by scarring, layering of the endocardium by thrombus, and
finally thrombus organization. Of interest, some patients have an
underlying hypereosinophilic myeloproliferative disorder driven by
constitutivelyactive platelet derived growth factor receptor (PDGFR)
tyrosine kinases (Chapter 11). Treatment of such patients with
tyrosine kinase inhibitors can result in hematologic remission and
reversal of the endomyocardial lesions.
62. Continuation
• Arrhythmogenic right ventricular dysplasia. In this rare type of
cardiomyopathy, the muscle in the lower right heart chamber (right
ventricle) is replaced by scar tissue. This can lead to heart rhythm
problems. This condition is often caused by genetic mutations.
Morphologically, the right ventricular wall is severely thinned owing
to myocyte replacement by massive fatty infiltration and lesser
amounts of fibrosis. Many of the mutations involve genes encoding
desmosomal junctional proteins at the intercalated disk (e.g.,
plakoglobin), as well as proteins that interact with the desmosome
(e.g., the intermediate filament desmin).
• Other types of cardiomyopathy. Other types of cardiomyopathy
(unclassified cardiomyopathies) exist, but they don't fit within the
other types of cardiomyopathy.
63. Continuation
Figure shows: Arrhythmogenic right
ventricular cardiomyopathy.The right
ventricle is markedly dilated with
focal, almost transmural replacement
of the free wall by adipose tissue and
fibrosis. The left ventricle has a
grossly normal appearance in this
heart; it can be involved (albeit to a
lesser extent) in some instances.
64. Continuation
Figure shows: Arrhythmogenic right
ventricular cardiomyopathy.The
right ventricular myocardium (red)
is focally replaced by fibrous
connective tissue (blue) and fat
(Masson trichrome
stain).
65. In the early stages, people with cardiomyopathy may not have any
signs and symptoms. But as the condition advances, signs and symptoms
usually appear. Cardiomyopathy signs and symptoms may include:
•Breathlessness with exertion or even at rest
•Swelling of the legs, ankles and feet
•Bloating of the abdomen due to fluid build-up
•Cough while lying down
•Fatigue
•Irregular heartbeats that feel rapid, pounding or fluttering
•Chest pain
•Dizziness, light-headedness and fainting
Symptoms
66. Diagnosis
Your doctor will conduct a physical examination, take a personal
and family medical history, and ask when your symptoms occur — for
example, whether exercise brings on your symptoms. If your doctor thinks
you have cardiomyopathy, you may need to undergo several tests to
confirm the diagnosis. These tests may include :
Chest X-ray
Echocardiogram
Treadmill stress test
Cardiac catheterization
Cardiac magnetic resonance imaging (MRI)
Cardiac computerized tomography (CT) scan
Blood tests
Genetic testing or screening
67. Treatment
The overall goals of treatment for cardiomyopathy are to manage
your signs and symptoms, prevent your condition from worsening, and
reduce your risk of complications. Treatment varies by which major
type of cardiomyopathy:
Dilated cardiomyopathy
If you're diagnosed with dilated cardiomyopathy, your doctor may
recommend treatment including:
Medications. Your doctor may prescribe medications to improve your
heart's pumping ability and function, improve blood flow, lower blood
pressure, slow your heart rate, remove excess fluid from your body or
keep blood clots from forming.
68. Continuation
Surgically implanted devices. If you're at risk of serious heart
rhythm problems, the doctor may recommend an implantable
cardioverter-defibrillator (ICD) — a device that monitors your heart
rhythm and delivers electric shocks when needed to control abnormal
heart rhythms.
In some cases, the doctor may recommend a pacemaker that
coordinates the contractions between the right and left ventricles
(biventricular pacemaker).
69. Continuation
Hypertrophic cardiomyopathy
If you're diagnosed with hypertrophic cardiomyopathy, the doctor may
recommend several treatments, including:
•Medications. The doctor may prescribe medications to relax your heart, slow
its pumping action and stabilize its rhythm.
•Implantable cardioverter-defibrillator (ICD). If you're at risk of serious
heart rhythm problems, your doctor may recommend an ICD to monitor your
heart rhythm and deliver electric shocks when needed to control abnormal heart
rhythms.
70. Continuation
•Septal myectomy. In a septal myectomy, your surgeon removes
part of the thickened heart muscle wall (septum) that separates the
two bottom heart chambers (ventricles). Removing part of the heart
muscle improves blood flow through the heart and reduces mitral valve
regurgitation.
•Septal ablation. In septal ablation, a small portion of the thickened
heart muscle is destroyed by injecting alcohol through a long, thin tube
(catheter) into the artery supplying blood to that area.
71. Continuation
Restrictive cardiomyopathy
Treatment for restrictive cardiomyopathy focuses on improving symptoms.
Your doctor will recommend you pay careful attention to your salt and water
intake and monitor your weight daily. Your doctor may also recommend you
take diuretics if sodium and water retention becomes a problem. You may be
prescribed medications to lower your blood pressure or control abnormal heart
rhythms.
If the cause of your restrictive cardiomyopathy is found, treatment will also be
directed at the underlying disease, such as amyloidosis.
72. Continuation
Arrhythmogenic right ventricular dysplasia
If you have arrhythmogenic right ventricular dysplasia, your doctor may
recommend treatment including:
•Implantable cardioverter-defibrillator (ICD). If you're at risk of
dangerous heart rhythms, your doctor may recommend an ICD. An ICD
monitors your heart rhythm and delivers electric shocks when needed to
control abnormal heart rhythms.
•Medications. If an ICD isn't appropriate to treat your condition, or if you
have an ICD and have frequent fast heart rhythms, your doctor may
prescribe medications to regulate your heart rhythm
73. Continuation
Radiofrequency ablation. If other treatments aren't controlling your
abnormal heart rhythms, your doctor may recommend radiofrequency
ablation. In this procedure, doctors guide long, flexible tubes (catheters)
through your blood vessels to your heart. Electrodes at the catheter tips
transmit energy to damage a small spot of abnormal heart tissue that is
causing the abnormal heart rhythm.
74. Continuation
Ventricular assist devices (VADs)
Ventricular assist devices (VADs) can help blood circulate through your heart.
They usually are considered after less invasive approaches are unsuccessful.
These devices can be used as a long-term treatment or as a short-term
treatment while waiting for a heart transplant.
Heart transplant
You may be a candidate for a heart transplant if medications and other
treatments are no longer effective, and you have end-stage heart failure.
75. Complication
Having cardiomyopathy may lead to other heart conditions, including:
Heart Failure
Blood Clots
Valve problems
Cardiac arrest and sudden death
77. Myocarditis
Myocarditis is an inflammatory disease of the myocardium with a wide
range of clinical presentations, from subtle to devastating. The image
below depicts numerous lymphocytes with associated myocyte
damage.
Figure shows: H and E, low power, showing numerous lymphocytes with
associated myocyte damage
78. Continuation
Myocarditis encompasses a diverse group of clinical entities in which
infectious agents and/or inflammatory processes primarily target the myocardium. It is
important to distinguish these conditions from those, such as IHD, in which
the inflammatory process is a consequence of some other cause of myocardial
injury.
79. Continuation
PATHOGENESIS
In the United States, viral infections are the most common cause of
myocarditis, with coxsackie viruses A and B and other enteroviruses accounting
for a majority of the cases. Cytomegalovirus (CMV), human immunodeficiency
virus (HIV), influenza virus, and others are less common pathogens. Offending
agents occasionally can be identified by nucleic acid footprints in infected
tissues, or by serologic studies showing rising antibody titers. While some
viruses cause direct cytolytic injury, in most cases the injury results
from an immune response directed against virally infected cells; this is
analogous to the damage inflicted by virus-specific T cells on hepatitis virus–
infected liver cells. In some cases viruses trigger a reaction against cross-
reacting proteins such as myosin heavy chain.
80. Continuation
The nonviral infectious causes of myocarditis run the entire
gamut of the microbial world. The protozoan Trypanosoma cruzi is the
agent of Chagas disease. Although uncommon in the northern
hemisphere, Chagas disease affects up to half of the population in
endemic areas of South America, with myocardial involvement in the
vast majority. About 10% of the patients die during an acute attack;
others can enter a chronic immune-mediated phase with development
of progressive signs of CHF and arrhythmia 10 to 20 years later.
Toxoplasma gondii (household cats are the most common vector) also
can cause myocarditis, particularly in immunocompromised persons.
Trichinosis is the most common helminthic disease with associated
cardiac involvement.
81. Continuation
Myocarditis occurs in approximately 5% of patients with Lyme
disease, a systemic illness caused by the bacterial spirochete
Borrelia burgdorferi. Lyme myocarditis manifests primarily as self-
limited conduction system disease, frequently requiring temporary
pacemaker insertion.
Noninfectious causes of myocarditis include lesions
associated with systemic diseases of immune origin, such as
systemic lupus erythematosus and polymyositis. Drug hypersensitivity
reactions (hypersensitivity myocarditis) also can occur with
exposure to any of a wide range of agents; such reactions typically are
benign and only in rare circumstances lead to CHF or sudden death.
82. Continuation
MORPHOLOGY
In acute myocarditis, the heart may appear normal or dilated; in advanced
stages, the myocardium typically is flabby and often mottled with pale and
hemorrhagic areas. Mural thrombi can be present.
Microscopically, active myocarditis is characterized by edema, interstitial
inflammatory infiltrates, and myocyte injury A diffuse lymphocytic infiltrate is
most common , although the inflammatory involvement is often patchy and can
be “missed” on endomyocardial biopsy. If the patient survives the acute phase
of myocarditis, lesions can resolve without significant sequelae or heal by
progressive fibrosis.
83. Continuation
Figure shows: Myocarditis with scarring. Short-axis gross photograph
of autopsy specimen from 8-year-old child with clinical myocarditis
shows scarring of both ventricles, more prominent in left ventricle.
Fibrosis shows random distribution with epicardial, myocardial, and
pericardial involvement.
84. Continuation
Figure shows: Myocarditis. A, Lymphocytic myocarditis, with edema and
associated myocyte injury. B, Hypersensitivity myocarditis, characterized
by perivascular eosinophil-rich inflammatory infiltrates. C, Giant cell
myocarditis, with lymphocyte and macrophage infiltrates, extensive myocyte
damage, and multinucleate giant cells. D, Chagas myocarditis. A myofiber
distended with trypanosomes is present, along with mononuclear
85. Continuation
In hypersensitivity myocarditis, interstitial and perivascular
infiltrates are composed of lymphocytes, macrophages, and a high
proportion of eosinophils. Giant cell myocarditis is a morphologically
distinctive entity characterized by widespread inflammatory cellular
infiltrates containing multinucleate giant cells (formed by macrophage
fusion). Giant cell myocarditis probably represents the aggressive end
of the spectrum of lymphocytic myocarditis, and there is at least focal—
and frequently extensive—necrosis . This variant carries a poor
prognosis. Chagas myocarditis is characterized by the parasitization
of scattered myofibers by trypanosomes accompanied by an
inflammatory infiltrate of neutrophils, lymphocytes, macrophages, and
occasional eosinophils.
86. Continuation
Clinical Features
The clinical spectrum of myocarditis is broad; at one end, the disease
is asymptomatic, and patients recover without sequelae. At the other
extreme is the precipitous onset of heart failure or arrhythmias,
occasionally with sudden death. Between these extremes are many
levels of involvement associated with a variety of signs and symptoms,
including fatigue, dyspnea, palpitations, pain, and fever. The clinical
features of myocarditis can mimic those of acute MI. Clinical
progression from myocarditis to DCM occasionally is seen.
88. Symptoms
Myocarditis usually manifests in an otherwise healthy person and can result in
rapidly progressive (and often fatal) heart failure and arrhythmia. Patients with
myocarditis have a clinical history of acute decompensation of heart failure, but
they have no other underlying cardiac dysfunction or have low cardiac risk.
Patients with myocarditis may present with the following signs and symptoms:
•Mild symptoms of chest pain (in concurrent pericarditis), fever, sweats, chills,
dyspnea
•In viral myocarditis: Recent history (≤1-2 wk) of flulike symptoms of fevers,
arthralgias, and malaise or pharyngitis, tonsillitis, or upper respiratory tract
infection
•Palpitations, syncope, or sudden cardiac death due to underlying ventricular
arrhythmias or atrioventricular block (especially in giant cell myocarditis)
•Heart failure
89. Continuation
Myocarditis in children
When children develop myocarditis, they might have signs and symptoms
including:
•Fever
•Fainting
•Breathing difficulties
•Rapid breathing
•Rapid or abnormal heart rhythms (arrhythmias)
90. Diagnosis
To diagnose myocarditis, your doctor may conduct a physical examination,
and discuss your medical history and any signs or symptoms you may have. If
your doctor suspects myocarditis, he or she might order one or more tests to
confirm the diagnosis and determine the severity of your condition, including:
Electrocardiogram (ECG)
Chest X-ray
MRI
Echocardiogram
Blood tests
Cardiac catheterization and endomyocardial biopsy
91. Treatment
In many cases myocarditis improves, either on its own or with treatment,
leading to a complete recovery. Myocarditis treatment focuses on treating the
underlying cause.
In mild cases, your doctor might tell you to rest and might prescribe medication
to help your body fight off the infection causing myocarditis while your heart
recovers. If bacteria are causing the infection, your doctor will prescribe antibiotics.
Although antiviral medications are available, they haven't proven effective in the
treatment of most cases of myocarditis.
92. Continuation
Certain rare types of viral myocarditis, such as giant cell and eosinophilic
myocarditis, respond to corticosteroids or other medications to suppress the
immune system response. In some cases caused by chronic illnesses, such as
lupus, the treatment is directed at the underlying disease.
Drugs to help your heart
If myocarditis is causing heart failure or rapid or irregular heartbeats as a
symptom, your doctor might hospitalize you. You might receive drugs or other
treatments to regulate your heartbeat if you have an abnormal heart rhythm
(arrhythmia). If you have certain abnormal heart rhythms or severe heart
failure, you may be prescribed medications to reduce the risk of blood clots
forming in your heart.
93. Continuation
If the heart is weak, the doctor might prescribe medications to reduce the
heart's workload or help eliminate excess fluid. These medications might
include:
•Angiotensin-converting enzyme (ACE) inhibitors. These medications,
such as enalapril (Vasotec), captopril (Capoten), lisinopril (Zestril, Prinivil) and
ramipril (Altace), relax the blood vessels in your heart and help blood flow
more easily.
•Angiotensin II receptor blockers (ARBs). These medications, such as
losartan (Cozaar) and valsartan (Diovan), relax the blood vessels in your heart
and help blood flow more easily.
•Beta blockers. Beta blockers, such as metoprolol (Lopressor, Toprol-XL),
bisoprolol (Zebeta) and carvedilol (Coreg), work in multiple ways to treat heart
failure and help control irregular or fast heart rhythms.
•Diuretics. These medications, such as furosemide (Lasix), relieve sodium
and fluid retention.
94. Continuation
Treating severe cases
In some severe cases of myocarditis, aggressive treatment might be
necessary, such as:
Intravenous (IV) medications.
Ventricular assist devices
Intra-aortic balloon pump
Extracorporeal membrane oxygenation (ECMO)
95. Complication
When myocarditis is severe, it can permanently damage your heart muscle.
This damage might cause:
Heart failure.
Heart attack or stroke.
Irregular heart rhythms (arrhythmias)
Sudden death.
97. Myocarditis and cardiomyopathy are a group of
disorders that primarily affect the myocardium in the
absence of hypertensive, congenital, ischemic or valvular
heart disease. The distinction between them is somewhat
arbitrary and not always made. Although, some people list
myocarditis as a subset of cardiomyopathy, few differences
help to distinguish the two conditions.
98. Comparison of Cardiomyopathy
and Myocarditis
Cardiomyopathy Myocarditis
Cardiomyopathy follows a chronic
course in which inflammatory features
are not prominent. Etiology of the
disease may be unknown or
associated with toxic, metabolic,
degenerative, amyloidosis, myxedema,
thyrotoxicosis or glycogen storage
diseases although they are very rare.
It is the acute inflammation of the
myocardium. In most of the occasions,
cause is idiopathic, but viral infections
found to be playing a major role. Most
common viral infections are coxsackie
virus B, mumps, influenza. Other
causes include autoimmune conditions
such as rheumatic fever, rheumatoid
arthritis, SLE, systemic sclerosis,
toxins, sarcoidosis and radiation
99. Cardiomyopathy Myocarditis
Cardiomyopathies are classified
according to the functional
disturbances as dilated, hypertrophic,
restrictive and obliterative. Histological
features are non specific. Irregular
atrophy and hypertrophy with
progressive fibrosis may be seen.
In myocarditis, heart is dilated, flabby
and pale. Small-scattered petechial
hemorrhages may be seen in the
myocardium. Microscopically cardiac
muscles are edematous and
hyperaemic. There can be infiltration
of lymphocytes, plasma cells and
eosinophils. Patient may be
asymptomatic and sometimes
recognized by the presence of an
inappropriate tachycardia or abnormal
ECG or from the features of heart
failure.
Comparison of Cardiomyopathy
and Myocarditis
100. Cardiomyopathy Myocarditis
Mostly patients are asymptomatic or
presents with features of acute
coronary syndrome. Chest pain is
common. In severe cases, there may
be associated heart failure,
arrhythmias and systemic
embolisation. ECG changes may be
present.
Biochemical markers of myocardial
ischemia are elevated in proportion to
the extent of damage. There may be
leukocytosis and raised ESR
depending on the cause.
Endomyocardial biopsy is diagnostic,
but it is performed rarely.
Comparison of Cardiomyopathy
and Myocarditis
101. Cardiomyopathy Myocarditis
Treatment depends on the type of
cardiomyopathy but mainly include
drugs, implanted pace makers,
defibrillators or ablation. Chronic
alcoholism is a recognized cause of
dilated cardiomyopahty and the effect
can be reversed with the cessation of
alcohol consumption for 10-20 years.
The prognosis depends on the
degree of impairment of myocardial
function and associated complications
Disease is self limiting. Management is
mainly supportive with antibiotic
therapy depending on the cause.
Arrhythmias and cardiac failure should
be treated accordingly. It is advised to
avoid intense physical exertion during
the active illness. The disease has an
excellent prognosis. But in severe
cases death may occur due to
ventricular arrhythmias and heart
failure.
Comparison of Cardiomyopathy
and Myocarditis
102. Differences between Myocarditis and
Cardiomyopathy
What is the difference between myocarditis and cardiomyopathy?
• Myocarditis is acute while cardiomyopathy is more of a chronic
condition.
• Myocarditis is usually caused my infectious agents and toxins, but
cardiomypathy is mostly genetic or may be associated with
degenerative conditions.
• In myocarditis features of acute inflammation in myofibrils are
prominent but it is not in cardiomyopahty.
• In myocarditis cardiac markers are elevated depending on the extent
of the damage.
• Myocarditis has a good prognosis.
• Management options are different in the two conditions.