Subject: Medicine II

Topic: 4.03c – Cardiomyopathy and Myocarditis

Lecturer: Dr. Clara Tolentino
Date: 11/10/15

OUTLINE  ARVC/D (arrythmogenic right ventricular cardiomyopathy or

I. Overview of Cardiomyopathy dysplasia) – right ventricle is infiltrated with fatty tissues. These
II. Dilated Cardiomyopathy fatty tissues can produce ventricular arrhythmias.
A. Infective Myocarditis Harrison’s:
a. Viral Myocarditis
o Genetic defects in proteins of the desmosomal complex
b. Parasitic Myocarditis
B. Non-infective Myocarditis disrupt myocyte junctions and adhesions, leading to
C. Takotsubo Cardiomyopathy replacement of myocardium by deposits of fat.
III. Toxic Cardiomyopathy o Thin ventricular walls may be recognized on ECG but are
A. Alcohol better visualized on MRI.
B. Chemotherapeutic agents  HCM (hypertrophic cardiomyopathy)
C. Metabolic Causes  DCM (dilated cardiomyopathy)
IV. Restrictive Cardiomyopathy
 LVNC (left ventricular non-compaction) – The fibers of the left
V. Hypertophic Cardiomyopathy
ventricle do not form normally. They are loose. These patients
OBJECTIVES have a tendency to have ventricular tachycardia. These can be
Objectives not given. seen by echo.
Harrison’s:
References: Harrison’s 19th Edition, Chapter 287. Ppt, Recording o Diagnostic criteria includes the presence of multiple
Legend: Italicized- from recording trabeculations in the left ventricle distal to the papillary
muscles, creating a “spongy” appearance of the apex; it has
I. OVERVIEW OF CARDIOMYOPATHY been associated with multiple genetic variants in the
 Diseases of the myocardium associated with mechanical and/or sarcomeric and other proteins such as tafazzin.
electrical dysfunction o Three cardinal clinical features are: ventricular arrhythmias,
 Excluding cardiac dysfunction that results from other structural embolic events, and heart failure.
heart disease, such as coronary artery disease, primary valve o Treatment: antiocoagulation and consideration for an
disease, or severe hypertension implantable defibrillator.
 Genetic, acquired, or both
 Heart failure symptoms, arrhythmias Table 1b. Table of genes associated with different classes of
cardiomyopathies. No need to memorize.
A. General Presentation
 Early symptoms: exercise intolerance with breathlessness or
fatigue due to inadequate cardiac reserve.
 Shortness of breath may occur during routine daily activity
 Dyspnea or cough when lying down at night.
 Patients with viral myocarditis have genes that make them at risk
for developing myocarditis. These patients will develop heart
failure symptoms and arrhythmias (supraventricular or ventricular
arrhythmias).

Table 1a. Table of genes associated with different classes of

cardiomyopathies. No need to memorize.

 There are genes which are responsible for production of

sarcomere, cytoskeleton, connecting membranes, excitation-
contraction coupling – responsible for difference in ion channels;
one of disease associated is Brugada Syndome.
 Brugada Syndrome is what we usually call ‘bangungot’ where
there is development of ventricular tachycardia or ventricular
fibrillation during sleep, especially after eating a heavy meal. It is
usually misdiagnosed as Pancreatitis.

Trans Group: Elaine, Karel, Diane, Dane Page 1 of 9

Edited By: Alie and Kimber
 Figure 1. Heart failure with preserved EF: Management.

 Heart failure with preserved EF – medications are not proven to

be effective. But we manage the risk factors, like HPN,
accordingly.

B. Initial Evaluation of Cardiomyopathy

Table 2. Evaluation of Cardiomyopathy

 Ask for history of sudden cardiac death.

 History of alcohol and ilicit drug use usually in the young
population.
 If you’re looking for hypertrophic cardiomyopathies, ARVD, or LV
non-compaction, it is most clearly seen through an MRI. MRI can
also differentiate an infarct from an infectious process.
 RV cannot be clearly evaluated through an Echo but adequately
seen through an MRI.
 Hyperthryroid checking may also be done by TF tests.
 Titers may be done if Viral Myocarditis is suspected.
 Endomyocardial Biospy – GOLD STANDARD; but yield is poor, you
won’t know which part to biopsy and not routinely done.

C. Classifications of Cardiomyopathy
 Dilated – enlarged LV: >55ml, may be low EF
 Restrictive – normal or decreased, may be low EF
 Hypertrophic – decreased diameter due to thick LV wall so
decreased internal diameter, high ejection fraction (EF)
o More of a relaxation dysfunction
o Ventricle is very thick it obstruct the outflow (aorta)
 All can have arrhythmias, HF symptoms (particularly dilated and
restrictive)

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Table 3. Presentation of Symptomatic Cardiomyopathy. (please see Table 4. Inflammatory Myocarditis and its Etiologies
appendix for larger photo) Lecturer mentioned that this table is
important.***

 In young patients, we see a lot of Viral Myocarditis, caused by

coxsackie and adenoviruses are most studied.
 In the case of Parasitic Myocarditis, Chagas’ disease is most
studied.

Infective Myocarditis
1. Viral Myocarditis
Figure 2. Gross specimen of a heart removed at the time of Etiopathogenesis:
transplantation shows massive left ventricular dilation and  Virus enters body and attaches to receptors of the heart
moderate right ventricular dilation. LV wall is thinned out. (Coxsackie-Adenovirus)
o This is further explained by the genetic predisposition of an
individual to develop myocarditis.
 Viral infection, replication, immune response
o All of which will cause damage to the myocardium

Clinical Manifestations:
 Chest pain
 HF (after a few days of viral prodrome)
 Arrhythmias – combination of different kind at the same time
o Ventricular tachycardia then after few seconds complete
block, then sinus bradycardia, etc.
 Fulminant – condition is rapidly progressive and develop
cardiogenic shock and multi organ failure.

Prognosis:
Figure 3. Echocardiogram of a young man with dilated  50% improve but can be fatal in some cases.
cardiomyopathy shows massive global dilation and thinning of the
walls of the left ventricle (LV). The left atrium (LA) is also enlarged Diagnostics:
compared to normal.  ECG, 2D echo, imaging, blood chemistry, endomyocardial biopsy.
 Other imaging such as MRI may also be used.
II. DILATED CARDIOMYOPATHY  Dallas Criteria
Harrison’s:
 Characterized by an enlarged left ventricle with decreased
systolic function as measured by left ventricular ejection fraction
 Systolic failure is more marked than the frequently
accompanying diastolic dysfunction, although the latter may be
functionally severe in the setting of marked volume overload

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 o Can be differentiated in MRI
Dallas Criteria for myocarditis on endomyocardial biopsy o Management is immunosuppression
include lymphocytic infiltrate with evidence of myocyte 2. Hypersensitivity myocarditis
necrosis and are negative in 80–90% of patients with  May be due to drugs such as antibiotics (product insert of
clinical myocarditis. Azithromycin indicates that it can develop myocarditis)

Negative Dallas Criteria can reflect sampling error or early
resolution of lymphocytic infiltrates, but also the
insensitivity of the test when inflammation results from
cytokines and antibody-mediated injury. Routine histologic
examination of endomyocardial biopsy rarely reveals a
specific infective etiology, such as toxoplasmosis or
cytomegalovirus.
o Possible subclinical acute myocarditis is diagnosed when a
patient has a typical viral syndrome but NO cardiac
symptoms, with one or more of the following:
 Elevated biomarkers of cardiac injury (troponin or CK-
MB).
 ECG findings suggestive of acute injury.
 Reduced left ventricular ejection fraction or regional wall
motion.
 Abnormality on cardiac imaging, usually
echocardiography
3. Peripartum cardiomyopathy
 Last trimester to 6 months after pregnancy
 Risk factors: Increased maternal age, increased parity, twin
pregnancy, malnutrition, use of tocolytic therapy for premature
labor, preeclampsia or toxemia of pregnancy
Tako-Tsubo Cardiomyopathy
 Tako-tsubo – apical ballooning or stress-induced cardiomyopathy
o Typically in older women after sudden intense emotional or
physical stress
o Global ventricular dilation with basal contraction, forming
the shape of the narrow-necked jar (tako-tsubo)
o Chest pain, heart failure
o ECG of acute infarction
o No therapy

o Probable acute myocarditis is diagnosed when the above

criteria are met and accompanied also by cardiac symptoms,
such as shortness of breath or chest pain, which can result
from pericarditis or myocarditis.
 When clinical findings of pericarditis (pleuritic chest pain,
ECG abnormalities, pericardial rub or effusion) are
accompanied by elevated troponin or CK-MB or abnormal
cardiac wall motion, the terms perimyocarditis or
myopericarditis are sometimes used.

o Definite myocarditis is diagnosed when there is histologic or

immunohistologic evidence of inflammation on
endomyocardial biopsy and does not require any other
III. TOXIC CARDIOMYOPATHY
laboratory or clinical criteria.
A. Alcohol
Management:
 Supportive therapy Table 5. Toxic Causes of Cardiomyopathy
 No specific therapy

2. Parasitic Myocarditis
Etiopathogenesis:
 Chagas’ disease – most common infective CMP (in the US, but not
in the Philippines)
o Trypanosoma cruzi, reduviid bug bite, blood transfusion,
organ donation, mother to fetus, orally
o Present in weeks to years
o Different arrhythmias  Alcohol is most common toxin
 Other causes include: trypanosomiasis, toxoplasmosis,  Excess consumption contribute to 10% of cases of HF
trichinellosis (see table 4.)

Non-infective Myocarditis (see table 4) Alcohol consumption necessary to produce cardiomyopathy:

1. Granulomatous Myocarditis 5-6 drinks daily for 5-10 years or
 Sarcoidosis and Giant cell myocarditis frequent BINGE drinking
 Sarcoidosis is more common than Giant cell
o Rapidly progressive
o May have different arrhythmias

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Harrison’s:
 Toxicity is attributed both to alcohol and to its primary C. Metabolic Causes
metabolite acetaldehyde. Table 7. Metabolic Causes of Cardiomyopathy
 Polymorphisms of the genes encoding alcohol dehydrogenase
and the angiotensin-converting enzyme increase the likelihood
of alcoholic cardiomyopathy.
 The cardiac impairment in severe alcoholic cardiomyopathy is
the sum of both permanent damage and a substantial
component that is reversible after cessation of alcohol
consumption
o If patient abstains from alcohol for 3-6 months
 Cocaine and amphetamines can produce:
o Chronic cardiomyopathy
o Acute ischemia  Thyroid Disease
o Tachyarrythmias o Rarely cause clinical HF, but can AGGRAVATE risk
o Pathology reveals tiny microinfarcts consistent with small o Clinical signs may be masked, so tests of thyroid function
vessel ischemia. Similar findings can be seen with are part of routine evaluation of cardiomyopathy
pheochromocytoma.  Diabetes
o Risk factor for HF – includes damage of small vessels
o Cardiomyopathy: due to insulin resistance and increased
B. Chemotherapeutic Agents
advanced-glycosation end products, which impair both
 Anthracyclines systolic and diastolic function
o Can cause histologic changes such as vacuolar degeneration
 Obesity alone is a risk factor
and myofibrillar loss
Table 8. Inherited Metabolic Defects
Harrison’s:
o Generation of reactive oxygen species involving heme
compounds is currently the favored explanation for myocyte
injury and fibrosis.
o Disruption of the large titin protein may be attributed to loss
of sarcomere organization.

Table 6. Presentations of Anthracycline-induced cardiomyopathy

Acute  During administration of single dose
 Clinically resolve in a few weeks
Early-  Develops in about 3% of patients
onset  It may rapidly be progressive but may resolve to
good, BUT not normal, ventricular function
Chronic  Years after
 Presentation differs whether therapy was given
before or after puberty

 Trastuzumab, cyclophosphamide, ifosfamide, 5-FU, cisplatin

Harrison’s:
o Trastuzumab is a monoclonal antibody that interferes with
cell surface receptors crucial for some tumor growth and for
cardiac adaptation. The incidence of cardiotoxicity is lower
than for anthracyclines but enhanced by coadministration Miscellaneous
with them. Trastuzumab cardiotoxicity does not always  Tachycardia-related cardiomyopathy – the patient may develop
resolve, some patients progress to clinical heart failure and enlargement of the heart. Once controlled, the heart goes back
death. to normal function.
o 5-FU and cisplatin can cause recurrent coronary spasm that
occasionally leads to depressed contractility. IV. RESTRICTIVE CARDIOMYOPATHY
 Tyrosine kinase inhibitors Harrison’s:
o Although these are “targeted” drugs, the biologic
 It is the least common of the triad of cardiomyopathies, which is
conservation of signaling pathways can cause these
dominated by abnormal diastolic function, often with mildly
inhibitors to have an “off-target” effects that include the
decreased contractility and ejection fraction.
heart
 Both atria are enlarged, sometimes massively.
 Other therapeutic drugs that can cause cardiotoxicity during
 End-diastolic pressures are elevated in both ventricles, with
chronic use include hydroxychloroquine, chloroquine,
preservation of cardiac output until late in the disease.
emetine, and antiretroviral therapies.
 Subtle exercise intolerance is usually the first symptom but is
often not recognized until after clinical presentation with

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 congestive symptoms.
 Often present with relatively more right-sided symptoms such as
edema, abdominal discomfort, and ascites, although filling
pressures are elevated in both ventricles.
 Cardiac impulse is less displaced than in dilated cardiomyopathy.
 A fourth heart sound is more common than a third heart sound
in sinus rhythm, but atrial fibrillation is common.
 Jugular venous pressures often show rapid Y descents, and may
increase during inspiration (positive Kussmaul’s sign).
 Most are due to infiltration of abnormal substances between
myocytes, storage of abnormal metabolic products within
myocytes, or fibrotic injury.
Table 9. Causes of Restrictive Cardiomyopathy
 Amyloidosis
o Major cause of restrictive cardiomyopathy
o An infiltrative disease: deposition of amyloid proteins
o Organ dysfunction due to: (1) physical disruption due to
infiltrating amyloid fibrils, (2) direct toxicity from Ig light
chain, (3) abnormal transthyerythin protein aggregates
o Management for heart failure, chemotherapy and heart
transplant (since it is a genetic problem, it does not improve)
o Symptoms of fluid retention: high doses of loop diuretics
Figure 4. Waxy appearance, atria are markedly dilated and left atrial
endocardium showing yellow-brown amyloid deposits
Figure 5. Echocardiogram showing: (1) thickened walls of both
ventricles without chamber dilatation, (2) atria are dilated consistent
with chronically elevated ventricular filling pressure, (3)
hyperrefractile “glittering” of the myocardium: typical of amyloid
infiltration
Figure 6. Left- shows grey-pink amorphous material infiltrating
between cardiomyocytes, which stain a darker pink ; Right- shows a
sulfated blue stain that highlights the amyloid green and stains the
cardiac myocytes yellow.
 Fabry’s disease
o X-linked recessive disorder that may also cause clinical
disease in female carriers
o Deficiency of lysosomal enzyme -galactosidase A
o Glycolipid accumulation in heart, skin, kidneys
o Electron microscopy shows diagnostic vesicles containing
concentric lamellar figures
 Glycogen storage disease
o Lead to accumulation of lysosomal storage products and
intracellular glycogen accumulation,
o Glycogen storage disease type III: due to a defective
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 debranching enzyme.
 Endomyocardial disease
o Hypereosinophilic syndrome (Loffler’s syndrome)
3
o >1,500 eos/ mm for at least 6 months
o Allergic, parasitic, malignant
o Management: Steroids, chemotherapy

IV. HYPERTROPHIC CARDIOMYOPATHY

 Most common genetic cardiovascular disease
 Most common cause of sudden cause of death in young adults:
usually in athletes
 1/ 500 individuals
 Autosomal dominant (56%)
Figure 9. (1) Disordered myocyte architecture with swirling and
 10 genes (80% of HCM)
branching rather than the usual parallel arrangement, (2) myocyte
 Sporadic (44%)
nuclei vary in size (3) interstitial fibrosis present
 Unexplained myocardial hypertrophy
 Focal or diffused
 Variable symptom severity and prognosis
 Predominantly involving intraventricular septum (IVS)
o Earlier the symptom the worse prognosis
o 30% with outflow obstruction: because intraventricular
o Pediatric presentation is associated increased early
septum is very thick, blood is unable to pass to aorta.
morbidity and mortality, the prognosis for those diagnosed
as adults is generally favorable
o Women more symptomatic
 Majority are asymptomatic or mildly symptomatic: they
will only when they develop syncope
 Heart failure, arrhythmias

Table10. Risk Factors for sudden Death in Hypertrophic

Cardiomyopathy

Figure 7. Asymmetrical septal hypertrophy (septum is twice more

than thickness of LV), endocardial fibrosis on the IVS

Figure 8. Asymmetrical septal hypertrophy compared to the lateral

wall of the left ventricle, LA is enlarged, the mitral valve is moving
anteriorly toward the hypertrophied septum in systole

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Figure 10. Treatment algorithm. ICD-implantable cardioverter- TEST YOURSELF! 
defribillator ICD
1. Typically seen in Restrictive Cardiomyopathy:
 Assess for risk of sudden death: if high risk consider implanting a. Asymmetrical hypertrop8hied septum
an ICD. b. Hyperrefractile “glittering” of the myocardium
 Symptomatic management: B-blockers, nondihydropyridine c. Thinning of the walls of the left ventricle (LV)
calcium channel blocker d. Endocardial fibrosis
 Avoid dehydration- want heart to be dilated, prevent collapse of
septum 2. A 23 year old college student was sent for an echocardiogram.
 Septal ablation There was an incidental note of a grade 3/6 midsystolic murmur
th
over the 5 ICS LMCL which increases in intensity with Valsalva
Harrison’s: 8maneuver. You may find the following in this patient’s
 Exertional dyspnea and chest pain are treated by medication to echocardiogram:
reduce heart rate and ventricular contractility with hopes of a. Asymmetrical hypertrophied septum
improving diastolic filling patterns. b. Aortic stenosis
 Beta-adrenergic blocking drugs and verapamil are most c. Pulmonic stenosis
commonly used as initial therapy.
d. Benign valvular regurgitation
o These agents act to decrease heart rate and increase the ANS: B, A
length of time for diastolic filling, as well as to decrease the
inotropic state.
 If there is fluid retention, diuretic therapy will usually be
necessary, but requires careful titration to avoid hypovolemia,
particularly in the presence of a resting or inducible obstruction
to ventricular outflow.
 When symptoms persist and an outflow gradient is present, an
addition of disopyramide is sometimes effective. Amiodarone
can also improve symptoms, but is usually initiated for control of
arrhythmias rather than symptoms.
 Anticoagulation is recommended to prevent embolic events for
patients who have had atrial fibrillation.
 Cardiac surgery can be directed to reduce the size of the upper
septum that contributes to the obstruction (myomectomy).
 Cardiac transplantation is considered in fewer than 5% of
patients with hypertrophic cardiomyopathy. It is more often
considered for patients who progress to “burned-out”
cardiomyopathy with decreased ejection fraction.

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 Subject: Medicine II
Topic: 4.03c – Cardiomyopathy and Myocarditis
Lecturer: Dr. Clara Tolentino
Date: 11/10/15

APPENDIX
Table 3. Presentation with Symptomatic Cardiomyopathy

Trans Group: Elaine, Karel, Diane, Dane Page 9 of 9

Edited By: Alie and Kimber