The

Cardiomyopathies
April 2007 Esayas K.G Jimma University 1
 Dilated cardiomyopathy
It is characterized by unexplained dilatation and
impaired contractile performance of one or both
ventricles.
DCM causes about third of cases of CHF.
Left &/or right ventricular systolic pumping function
is impaired, leading to progressive cardiac
enlargement and hypertrophy by remodeling.
Symptoms of CHF typically appear only after
remodeling has been ongoing for months or even
years. There is however, no correlation between the
degree of contractile dysfunction & severity of the
April 2007 Esayas K.G Jimma University 2

symptoms.
Etiology:-
 No cause is apparently known.
 Thought to be the end result of myocardial damage produced by a variety of
toxic, metabolic, or infectious agents.
 It may be the late sequellae of acute viral myocarditis, possibly mediated by an
autoimmune mechanism.
 Reversible forms of DCM occur in:
 Alcohol abuse
 Pregnancy
 Thyroid disease
 Cocaine abuse
 Chronic uncontrolled tachycardial
 20-40% of patients have familial forms of disease with mutations of genes
encoding cytoskeletal, contractile, and nuclear membrane proteins.
 It is typically heterogeneous but most commonly autosomal dominant
transmission;autosomal recesive, mitochondrial, and x-linked inheritance may
also be seen.
 Right ventricular dyplasia is a unique familial cardiomyopathy marked
by progressive replacement of the right ventricular wall with adipose tissue. It is
often associated with ventricular arrhythmias & sudden death.

April 2007 Esayas K.G Jimma University 3

Epidemiology:-occurs worldwide
 Is commonly a disease of middle age men
 Prevalence is increasing currently
Clinical features:-
 Sxs. of biventricular failure develop gradually in most
patients.
 Some pts have LV dilatation for months or even years
before becoming symptomatic.
۞
 Syncope due to arrhythmia
 Thromboembolism(ventricular thrombus)
 Non-specific chest pain
 Note:-presence of typical angina pectoris is unusual &
suggests the presence of concomitant ischemic heart
disease.
April 2007 Esayas K.G Jimma University 4
Physical examination:-
 Shifted PMI→ cardiac enlargement
 Signs of CHF
 Third and 4th heart sounds are commonly found
 MR/TR may occur
 In advanced disease
 Narrow pulse pressure
 Raised JVP

April 2007 Esayas K.G Jimma University 5

Investigations
 CXR:- cardiomegaly, significantly LV
 ↑ed vascular markings
 Signs of interstial or alveolar edema
 ECG:-sinus tachycardia
 AF
 Ventricular arrhythmia
 LA abnormalities
 Diffuse non-specific ST-T wave abnormalities
 Sometimes interventricular conduction defects & low voltage.

 Echo.:-LV dilatation with normal, minimally thickened, or thinned

wall.
Systolic dysfunction (↓ed EF)
 Cardiac catheterization & coronary angiography are often
performed to exclude IHD.
 Angiography shows dilated, diffusely hypokinetic LV with some
degree of MR.
April 2007 Esayas K.G Jimma University 6
Management
 Standard therapy of heart failure with:
 Salt restriction
 ACEi/ARB
 Diuretics produce symptomatic improvement
 digitalis
 β-blockers
 spironolactone for patients with recent or current advanced HF
 Avoid: - alcohol
Calcium channel blockers
NSADs
 Systemic embolization is a concern→consider chronic anticoagulation
 Antiarrhythmic are best avoided for fear of proarrhythmia, unless
they are needed to treat symptomatic or serious arrhythmias.
 ICD- is useful for patients with symptomatic ventricular arrhythmias
 cardiac transplantation!-In patients with advanced disease who
are refractory to medical therapy.
April 2007 Esayas K.G Jimma University 7
Prognosis
 Most patients have a downhill course
 Majority particularly those > 55 yrs die within 3
yrs of Sx.
 Death is usually due to either CHF or ventricular
tachy−or bradyarrhythmiacardia.
 Sudden death is a constant threat.
 Spontaneous improvement or stabilization occurs
in about a quarter of patients.

April 2007 Esayas K.G Jimma University 8

 Restrictive cardiomyopathy
 It is the rarest of the three types of CMP. It is more common in
countries such as equatorial Africa where it is acquired 2o to
endomyocardial disease.
 RCMs arise from loss of ventricular distensibility as a result of
either myocardial or endomyocardial disease.
 The pathologic hallmark is myocardial fibrosis, hypertrophy, or
inflammation due to variety of causes.
 The most common cause is endomyocardial fibrosis (EMF),
which often occurs in association with eosinophilia
( hypereosinophilic syndrome).
 Other causes are:
Amyloidosis
Hemochromatosis
Glycogen deposition
Sarcoidosis
Fabry’s disease
Scleroderma
Mediastinal radiation
April 2007
Neoplastic infiltration Esayas K.G Jimma University 9
 …continued
 The hemodynamic hallmark of RCM is abnormal
diastolic function; the ventricular walls are
excessively rigid and impede ventricular filling.
 There is partial obliteration of the ventricular cavity
by fibrous tissue and thrombus: -
 Abnormally ↑ed resistance to ventricular filling
 Thromboembolic complications in 1/3rd of patients
 The inability of ventricles to fill limits cardiac
output and raises filling pressure.

April 2007 Esayas K.G Jimma University 10

Clinical features
 Exercise intolerance & dyspnea are usually the most
prominent symptoms.
 Dependent edema, ascites, & hepatomegaly
 Raised JVP with Kussmaul’s sign
 Heart sounds may be distant & 3rd & 4th heart sounds
are common
 RCM resembles constrictive Pericarditis in most
cases, in RCM apical impulse is usually easily
palpable, & MR is more common.

April 2007 Esayas K.G Jimma University 11

Investigation: -
 ECG: - low voltage, non-specific ST-T wave changes &
various arrhythmias.
 ECHO: -
 symmetrically thickened left ventricular walls & normal or
slightly reduced ventricular volume & systolic function
 Doppler recordings demonstrate accentuated early diastolic filling.

 Cardiac cathetherizatiion: -
 ↓ed cardiac output
 Elevation of the right and left ventricular end-diastolic pressure &
plateau configuration of the diastolic portion of the ventricular
pressure pulse
 Endomyocardial Bx differentiate RCM from
CT/MRI constrictive pericarditis
April 2007 Esayas K.G Jimma University 12
Treatment: -
 The treatment is as for any cardiac failure-but
usually disappointing.
 Chronic anticoagulation is often recommended
 Cardiac transplantation

April 2007 Esayas K.G Jimma University 13

 Hypertrophic Cardiomyopathy
 Hypertrophic cardiomyopathy (HCM) is a complex but a common
form of genetic heart disease typically inherited in an autosomal
dominant fashion with variable penetrance and expressivity.
 HCM is the leading cause of sudden cardiac death in people under 30
years and responsible for exercise disability at almost any age.
 It is characterized by a hypertrophied and non dilated left and/or right
ventricles in the absence of obvious causes like AS or HTN.
Prevalence: is 0.2% of the general population:
Sex:
 HCM is identified slightly more commonly in males than in females.
However, the genetic inheritance pattern is autosomal dominant, without
gender predilection.
 HCM usually presents at an earlier age in females than in males. Females
with HCM tend to be more symptomatic and are more likely to be disabled
by their symptoms.
Age:
 HCM may occur at any age from newborn to elderly.
 HCM is a progressive condition that worsens over time if left untreated.
 Its most common presentation is in the third decade of life.
April 2007 Esayas K.G Jimma University 14
Causes:
 The actual cause of HCM is defects in the genes encoding for several of the
sarcomeric proteins.
 Genetic causes: -
 About 50% of all patients with HCM have positive family history
compatible with autosomal dominant transmission..
 Familial HCM is a genetically heterogeneous disease because it is
caused by defects at multiple genetic loci.
 At least 12 different genes on at least 6 chromosomes are associated
with HCM, and more than 200 different mutations have been
discovered.
 40% of these are associated with mutations of the cardiac β-
myocin heavy chain gene on chromosome-1
 15%-mutation of cardiac troponin T gene on chromosome-1
 20%-mutations of myosin binding protein c (chromosome 11)
 5%-mutation of α-tropomyosin gene

April 2007 Esayas K.G Jimma University 15

 Echocardiographic studies have confirmed that
about 1/3rd of the 1st degree relatives of patients
with HCM have evidence of the disease.
Other suggested causes of HCM are:
Abnormal calcium kinetics:
 ↑ed intracellular calcium concentration as a result of ↑ed
no. of calcium channels→ myocardial hypertrophy &
disarray.
Abnormal sympathetic stimulation
 ↑ed responsiveness of heart to catecholamines
 Excessive production of cathecholamines
 ↓ed neuronal uptake of catecholamines

Cardiac structural abnormalities

April 2007 Esayas K.G Jimma University 16
Pathology:
 The right, the left, or both ventricles may be
involved.
 RVH is :
 usually symmetric
 Seen in over 30% of patients
 Isolated RVH is rare

• Hypertrophy on the left is usually asymmetric,

involving the interventricular septum & the free wall
than the posterior wall.

April 2007 Esayas K.G Jimma University 17

LVH
Over 60% of patients will have structural abnormalities
of MV(↑leaflet area, elongation of leaflets, or anomalous
April 2007 Esayas K.G Jimma University 18
papillary muscle insertion into the anterior MV).
 The two important features of LVH: -
2. Heterogeneous hypertrophy, often with
preferential hypertrophy of the interventricular
septum resulting in asymmetric septal
hypertrophy (ASH).
3. A dynamic left ventricular outflow tract pressure
gradient, related to a narrowing of the subaortic
areas as a consequence of SAM of the MV.
The pathophysiologic abnormality is diastolic
dysfunction characterized by increased stiffness
of the hypertrophied muscle →↑diastolic filling
pressure & is present despite a hyperdynamic LV.
April 2007 Esayas K.G Jimma University 19
Hemodynamics: -
 Many individuals with HCM demonstrate left ventricular
dynamic out flow obstruction.
 The degree of obstruction is variable and is dependent on the
amount of blood in the ventricles immediately before ventricular
systole.
 Dynamic outflow obstruction is always due to SAM of MV
against the hypertrophied septum.
 The three basic mechanisms of dynamic changes resulting
in pressure gradient are:-
1. Increased left ventricular contractility
2. Decreased ventricular volume (Preload)
3. Decreased aortic impedance & pressure (After load)
♣ Conditions that increase myocardial contractility (exercise,
sympathomimetics, & digitalis glycosides) and those that
decrease ventricular volume (valsalva maneuver,
nitroglycerine, amyl nitrates & tachycardia) aggravate it.
April 2007 Esayas K.G Jimma University 20
C/F
 Clinical feature is highly variable:
 Many are asymptomatic or mildly symptomatic &
may be relatives of patients with known disease.
 The first manifestation of the disease may be sudden
cardiac death, in childhood or adolescents, often
during or after physical exertion.
 The arrhythmia that causes sudden death is
ventricular fibrillation in more than 80% of
individuals with HCM.

April 2007 Esayas K.G Jimma University 21

In symptomatic patients, common symptoms are:
 Dyspnea
 It is the most common presenting symptom of HCM occuring in
as many as 90% of symptomatic patients.
 Syncope
 Syncope is a common symptom of HCM, resulting from
inadequate cardiac output on exertion or from cardiac
arrhythmia.
 Presyncope( near syncope= "graying out" spells)
 Angina
 Palpitations
 Orthopnea and paroxysmal nocturnal dyspnea
 Symptoms of Congestive heart failure
 Dizziness
 Note:-symptoms are not closely related to the
presence or severity of an outflow pressure
gradient.
April 2007 Esayas K.G Jimma University 22
Physical Examination: -
 Most patients with gradients demonstrate a double or triple
apical precordial impulse, a rapidly rising carotid arterial
pulse, & 4th heart sound.
 The hallmark of obstructive HCM is a systolic crescendo-
decrescendo murmur is heard best between the apex and left
sternal border; it radiates to the suprasternal notch but not to
the carotid arteries or neck.
 The murmur and the gradient across the LV outflow tract diminish
with any increase in preload or increase in afterload and increase
with any decrease in preload or afterload
 Holosystolic murmur of mitral regurgitation is heard in
patients with SAM of the MV and significant LV outflow
gradients.
April 2007 Esayas K.G Jimma University 23
Investigations
 CXR- usually normal ( occasionally increased cardiac
silhouette)
 Electrocardiography
 ECG is normal in 5% of symptomatic & 25% of asymptomatic
patients.
 At the time of diagnosis, 10% are in AF
 Majority of them have an interventricular conduction delay.
 ST segment depression and T-wave changes are the most common
abnormalities associated with voltage changes of LVH.
 Wide speared, deep , broad Q waves in the inferior leads that suggest an
old MI
 Left axis deviation
 Arrhythmia-SVT, AF, VT
 conduction abnormalities (i.e., PR prolongation, bundle branch block,
Wolff-Parkinson-White syndrome ),
 P-wave abnormalities of left &/or right atrial overload (atrial
April 2007 enlargement). . Esayas K.G Jimma University 24
Echocardiography- mainstay of diagnosis for HCM.
 LVH > 13 mm (usually >15mm),septum often 1-3 or
more times thicker than the high posterior free wall and
at least 4-6 mm thicker than normal for each age group.
 Echocardiography also typically reveals diastolic
dysfunction with reduced LV compliance.
 The hallmarks of the obstructive type of HCM consist of SAM
of the anterior MV and ASH, with a septal wall thickness-to-
posterior wall thickness ratio greater than 1.4:1.
 Other echocardiographic findings in individuals with
HCM may include the following:
 Small LV cavity.
 Reduced septal motion and thickening during systole,
 Normal or increased motion of the posterior wall
 Left atrial enlargement

April 2007 mitral regurgitationEsayas K.G Jimma University 25
Exercise testing:
 About third of pts. Will have an abnormal BP response
 ST segment changes associated with symptoms of
angina, are found in 25% of pts.
Radionuclide imaging with thallium or technetium
may demonstrate reversible defects.
Cardiac catheterization
Histologic Findings: bizarre and disorganized
arrangements of cardiac muscle cells ( cell-to-cell
disarray) and myocardial fibrosis of the septum.

April 2007 Esayas K.G Jimma University 26

 Differentiating hypertrophic cardiomyopathy and valvular aortic stenosis

Aortic stenosis Hypertrophic cardiomyopathy

Echocardiography

Aortic valve
Common No
calcification
Dilated ascending
Common Rare
aorta
Ventricular
Concentric Asymmetric, often involving the septum
hypertrophy

Physical examination

Murmur of AI Common No

Pulse pressure after

Increased Decreased
PVC
Decreased intensity of
Valsalva maneuver Increased intensity of murmur
murmur

Brisk, jerky, or bisferiens pulse (a collapse of

Carotid pulsation Normal
April 2007 Esayas K.G the pulse followed by a secondary rise) 27
Jimma University
Criteria to differentiate b/n HCM and Athlete’s heart
HCM Athlete’s
Heart
(
Physiologic
LVH)
Distribution of Mostly Substantially
hypertrophy asymmetrical symmetrical
Max. LV wall >16 <16
thickness (mm)
LV cavity Normal or ↓ed Normal or ↑ed (≥55)
dimension(mm) (< 45)
LV filling and Usually Normal
relaxation abnormal
Regression of LVH Absent or Present
with detraining marginal
Marked ECG common uncommon
abnormalities
Familial evidence of usually present Absent
April 2007
HCM Esayas K.G Jimma University 28

Peak O2 consumption Normal or ↓ed >5o ml/kg/min

Management
 Treatment of HCM is directed towards decreasing
the LV outflow tract gradient and symptoms of
dyspnea, chest pain & syncope.
 Treatment options for pts with HCM depend upon
the heart condition & severity of symptoms, and are
intended to decrease the stress on the heart and
relieve symptoms.

April 2007 Esayas K.G Jimma University 29

• Medical Therapy:
It is successful in majority of pts.
Medications help relax the heart & reduce the degree of obstruction.
b. β-blockers (metoprolol, atenolol, bisoprolol, propranolol)
 ↓outflow obstruction & ↑ventricular compliance
c. Calcium channel blockers (verapamil, deltiazem)
 Are alternative to β-blockers
 Improve diastolic filling by improving diastolic relaxation & decreasing
outflow gradient due to depression of cardiac contractility.
Note:-Nifedipine should be avoided!
 β-blockers + calcium channel blockers should used cautiously.
d. Amiodarone (class III antiarrhythmic agent)
 Its use is generally reserved for potentially life-threatening ventricular
arrhythmias
 Reduces risk of SCD
e. Disopyramide (class-I antiarrrhytmic agent)
Pharmacologic therapy is primarily intended to alleviate the symptoms associated with
HCM,
no drug has been shown to alter the natural history of the disease in either symptomatic
or asymptomatic patients. Esayas K.G Jimma University
April 2007 30
1. Transvenous dual-chamber permanent pacing
↓ LV outflow obstruction by altering the pattern of ventricular depolarization and contraction.
Doesn’t reduce risk of ventricular arrhythmias & sudden death
Used as adjunct with medical therapy

1. Septal Alcohol ablation

April 2007 Esayas K.G Jimma University 31
 • Implantable cardioverter defibrillator (ICD)
 Indicated in patients:
 Who survive cardiac arrest
 With high risk ventricular arrhythmias
 ↓SCD
 Superior to antiarrhytmiac drug therapy

April 2007 Esayas K.G Jimma University 32

 Surgical Mgt.( Myectomy):
 Indications:
 Severe symptoms refractory to medical therapy
 Outflow gradient of >50mmHg either provocation or at rest
 Cardiac transplantation!

April 2007 Esayas K.G Jimma University 33

GENERAL MANGEMENT OF PATIENTS WITH HCM
 Advise individuals with HCM to avoid strenuous activity, anaerobic
exercise such as weight lifting. Don’t permit competitive level sports
if any of the following are present:
 Significant outflow gradient
 Significant ventricular or supraventricular arrhythmia
 Marked LVH
 Hx. of sudden death in relatives with HCM
 Confirmed malignant genotype
 Avoid administration of inotropic agents
 Avoid nitrates & sympathomimetic amines except in pts. with HCM
& concomitant coronary artery disease.
 Cardiac glycosides are contraindicated except in pts. with
uncontrolled AF.
 ACEi and ARB are better avoided.
 Avoid diuretics because of their effect on Left ventricular volume.
 Alcohol ingestion should be avoided; even social alcohol ingestion
may induce sufficient VD to exacerbate an outflow pressure gradient.
 First degree relatives of patients with HCM should be screened by
echocardiography.
April 2007 Esayas K.G Jimma University 34
 Complications of HCM:
2. Congestive heart failure
 observed in individuals with severe cases of HCM.
 It may occur as a result of a combination of impaired diastolic
function and subendocardial ischemia.
 Patients with CHF have a high likelihood of recurrent heart
failure due to both mitral regurgitation and profound diastolic
dysfunction.
3. Atrial fibrillation with mural thrombosis formation
 Common late in the course of the disease
 Anticoagulation is necessary in patients with chronic AF
4. Other types of arrhythmia (ventricular fibrillation,
supraventricular tachycardia associated with Wolff-
Parkinson-White syndrome, ventricular tachycardia),
5. Infective endocarditis-occurs in 10% of patients
→Prophylaxis is indicated in patients with resting
obstruction and MR
April 2007 Esayas K.G Jimma University 35
• Myocardial ischemia:-despite normal epicardial
coronary arteries,myocardial ischemia is common
in HCM.
Potential causes of the ischemia are:
 Increased muscle mass
 Elevated diastolic filling pressures
 Enhanced myocardial O2 demand (increased wall stress)
 Systolic compression of arteries
 Impaired vasodilator reserve
3. Sudden death

April 2007 Esayas K.G Jimma University 36

 Prognosis:
 Natural history is variable
 HCM frequently causes no or only mild disability
over a life time, and many patients achieve normal
life expectance.
 In symptomatic ones it is a chronic illness with
lifestyle restrictions.
 Mortality rate in individuals with HCM is 4% per
year.
 The major cause of death in HCM is sudden cardiac
death that may occur in asymptomatic patients.
April 2007 Esayas K.G Jimma University 37
Predictors of SCD are:
2. Age < 30yrs.
3. Patients with prior cardiac arrest
4. Patients with family Hx of sudden death due to
HCM
5. Recurrent syncope or any Hx of syncope during
childhood
6. Marked ventricular hypertrophy ( >30mm)
7. Sustained supraventricular or ventricular
tachycardia
8. Hypotensive response to exercise testing
9. Specific mutations in genes encoding for troponin
T & myosin.
April 2007 Esayas K.G Jimma University 38
Identifiable & treatable mechanisms of SCD in
HCM
 Paroxysmal AF-amiodaron
 Sustained monomorphic VT- amiodaron + ICD
 Ischemia-high dose verapamil
 Conduction disease-pacemaker
 Accessory pathway -ablation

April 2007 Esayas K.G Jimma University 39

There is no correlation between the risk
of sudden death & the severity of
symptoms or the presence or severity of
the outflow tract pressure gradient!

April 2007 Esayas K.G Jimma University 40

 References
 Harrison’s principles of Internal Medicine, 16th
edition, 2005.USA
 Concise Oxford Text Book of Medicine, 2000. UK
 European Journal of Cardiovascular prevention
and Rehabilitation
 UpToDate online, 15.1, Feb.2007
 Online References

April 2007 Esayas K.G Jimma University 41