Cardiomyopathies

1. CARDIOMYOPATHY
Department of Medicine

2. LEARNING OUTCOMES
At the end of this lecture, students should be able to:
• Define cardiomyopathy
• Discuss the pathophysiology of cardiomyopathy
• Classify cardiomyopathies and distinguish between
Dilated, Hypertrophic, and Restrictive cardiomyopathy
• Outline the clinical manifestations of each cardiomyopathy
subtype
• Describe the diagnostic studies used in the management
of cardiomyopathy
• Describe the pharmacologic and non-pharmacologic
therapies used in treatment of cardiomyopathy

3. Definition
• “A myocardial disorder in which the heart muscle is
structurally and functionally abnormal, in the absence of
coronary artery disease, hypertension, valvular disease
and congenital heart disease sufficient to cause the
observed myocardial abnormality”

4. Definition
• Heterogeneous group of diseases of the myocardium
associated with mechanical and/or electrical dysfunction
that usually (but not invariably) exhibit inappropriate
ventricular hypertrophy or dilatation and are due to a
variety of causes that frequently are genetic.
• Cardiomyopathies either are confined to the heart or are
part of generalized systemic disorders, often leading to
cardiovascular death or progressive heart failure–related
disability.

5. Classification
ESC 2007
●Dilated cardiomyopathy (DCM)
●Hypertrophic cardiomyopathy (HCM)
●Restrictive cardiomyopathy (RCM)
●Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D

6. PRIMARY CARDIOMYOPATHIES – In which the clinically relevant
disease processes solely / predominantly involve the myocardium

7. • Storage:
– Haemochromatosis
– Fabry’s disease
– Glycogen storage disease
Type II
– Niemann-Pick disease
• Autoimmune/collagen
– SLE
– Dermatomyositis
– Rheumatoid arthritis
– Scleroderma
– Polyarteritis nodosa
• Infiltrative:
– Amyloidosis
– Gaucher disease
– Hurler’s disease
– Hunter’s disease
• Neuromuscular/Neurological
– Friedreich’s ataxia
– Duchenne-Becker muscular
dystrophy
– Myotonic dystrophy
– Neurofibromatosis
– Tuberous sclerosis
Secondary Cardiomyopathy:
SECONDARY CARDIOMYOPATHIES (AHA Classification)

8. • Endocrine
– Diabetes Mellitus
– Hyper/hypothyroidism
– Pheochromocytoma
– Acromegaly
• Inflammatory
– Granulomatous
• Sarcoidosis
• Toxicity
– Drugs-Antiretroviral agents/Cocaine
– Alcohol
– Chemical and Heavy Metals
• Consequence of cancer
therapy
– Anthracycline
• Doxorubicin
• Daunorubicin
– Cyclophosphamide
– Radiation
• Cardiofacial
– Noonan syndrome
– lentiginosis
SECONDARY CARDIOMYOPATHIES (AHA Classification)

9. Characteristics
• Dilated Cardiomyopathy (DCM)
• Left +/- Right Ventricular Hypertrophy
• Impaired contraction
• Systolic dysfunction
• Hypertrophic Cardiomyoapthy (HCM)
• Left+/-Right Ventricular Hypertrophy
• Diastolic dysfunction
• End-stage can resemble DCM
• Restrictive Cardiomyopathy (RCM)
• Impaired ventricular filling
• Diastolic dysfunction
• Arrythmogenic right ventricular cardiomyopathy (ARVC)
• Fibrous or fibro-fatty replacement of myocardium in the inflow tract, outflow tract and/or
apex of the RV
• Global right ventricular dilatation & dysfunction
• Unclassified
• Doesn’t fit into the above

10. Dilated cardiomyopathy (DCM)
Epidemiology
• Prevalence
– Incidence 5-8/100,000
– Prevalence (US)
36/100,000
– Racial difference
– Most commonly becomes
clinically apparent in the
3rd or 4th decade
• Mostly autosomal
dominant

11. • Inflammatory infiltrate of the myocardium
• Acute (active) myocarditis requires myocyte necrosis ±
degeneration
• Distribution
– Focal, confluent, diffuse
• Subclassified by cell type
– Lymphocytic, Eosinophilic, Neutrophilic, Giant cell,
Granulomatous, Mixed
DCM – Definition: World Health Federation

13. DNA
Mutation
Altered
gene
product
T-Cell activation
?Autoantibodies
?Cytokines
Myocarditis
Viral
persistence
DILATED
CARDIOMYOPATHY
Virus
Autoimmunity
Genetics
Myocardial
Dysfunction
dapted from Mestroni et al BHJ 1997;72:S35
DCM: Causes

14. Hypertrophic Cardiomyopathy (HCM)
HCM Pathology
Disarray
Fibrosis
Hypertrophic Cardiomyopathy
 Left ventricular hypertrophy in the absence
of any stimulus such as hypertension and
valve disease
HCM can be defined as the unexplained,
asymmetrical or concentric hypertrophy of
the undilated left ventricle. There is also
hypertrophy of the right ventricle

15. HCM
Epidemiology and Public / International Health
• One of the most common inherited cardiac disorders (affecting ~1:500)
• Number one cause of sudden cardiac death in young athletes
• Annual mortality is estimated at 1-2 %
Genetics
• Heterogeneous disorder caused by mutations in multiple genes coding
for mainly sarcomeric proteins (beta-myosin heavy chain, troponin T)
• Majority missense
• Incomplete/age related penetrance
• Variable penetrance
• Primarily autosomal dominant, over 150 mutations have been identified

16. HCM: Pathophysiology and
Clinical Features
The following processes are responsible for the clinical manifestations
of HCM
• The most commonly observed pattern is Asymmetrical Septal
hypertrophy (ASH). This pattern is classically associated with
systolic anterior motion (SAM) of the mitral valve and dynamic
left ventricular outflow tract (LVOT) obstruction.
• However, in the majority of cases (75%), HCM is not associated with
LVOT obstruction (hence the name change from HOCM to HCM).
• Other less common patterns of LVH include concentric hypertrophy
(20% of cases) and apical hypertrophy (10%).

17. HCM: Pathophysiology and
Clinical Features
The following processes are responsible for the clinical manifestations
of HCM
• Dynamic obstruction of the LVOT
– Left ventricular diastolic dysfunction resulting from impaired
relaxation and filling of the stiff and hypertrophied left ventricle
(often associated with increased filling pressures)
– Abnormal intramural coronary arteries with thickened walls and
narrowed lumens
– Chaotic, disorganized left ventricular architecture (“cellular
disarray”) predisposing to abnormal transmission of electrical
impulses and thus serving as a substrate for arrhythmia

19. HCM: Symptoms
• Exertional syncope or pre-syncope
• Chest pain — may be typical anginal pain due to increased
demand (thicker myocardial walls) and reduced supply
(aberrant coronary arteries).
• Palpitations due to supraventricular or ventricular
arrhythmia
• Dyspnoea from pulmonary congestion
• Sudden Cardiac Death (SCD)

20. HCM: Signs
• Jerky pulse
• JVP: large a waves, indicating right ventricular flow obstruction
• Double apical impulse
• Loud fourth heart sound due to the left ventricular hypertrophy
• Third heart sound
• Late systolic murmur:
– this is a result of outflow tract obstruction with or without MR
– the murmur is late in systole because some blood must be
ejected from the ventricle before the outflow is obstructed
– the murmur is louder during a Valsalva manoeuvre
– the murmur is softer when squatting

21. HCM – ECG
• Left ventricular hypertrophy results in increased precordial voltages and non-specific ST segment and T-wave abnormalities.
• Asymmetrical septal hypertrophy produces deep, narrow (“dagger-like”) Q waves in the lateral (V5-6, I, aVL) and inferior (II, III, aVF)
leads. These may mimic prior myocardial infarction, although the Q-wave morphology is different:
• Atrial fibrillation and supraventricular tachycardia are common. Ventricular dysrhythmias (e.g. VT) also occur and may be a cause of
sudden death.

22. HCM – Imaging
• ECHO (TTE)
• Cardiac MRI Fibrosis

24. HCM: Treatment
Hypertrophic Cardiomyopathy
Genetics
Inheritance
Insurance
Employment
Psychology
Risk
of Complications
Sudden Death
Thromboembolism
Infective Endocarditis
Heart Failure
Symptoms

25. HCM: Interventional Vs. Surgical
Septal Ablation Septal Myomectomy
Septal Ablation for HCM
• Sigwart reported 3 pts, 1995
• Alcohol injected into 1st septal
perforator t
o c
r eate a “localised
myocardial infarction”
• Advantages of nonsurgical procedure
– Faster recovery
– Less pain
– Fewer complications??
– Quick return to daily lifestyle

26. Restrictive Cardiomyopathy (RCM)
• RCM characterized by a pattern of ventricular filling in which
increased stiffness of the myocardium causes ventricular
pressure to rise precipitously with only small increases in
volume.
• RCM has always been difficult to define because restrictive
ventricular physiology occurs in a wide range of different
pathologies.
• RCM defined as restrictive ventricular physiology in the
presence of normal or reduced diastolic volumes (of one or
both ventricles), normal or reduced systolic volumes, and
normal ventricular wall thickness.

27. RCM - Epidemiology
• The exact prevalence of RCM is unknown but it is probably the least
common type of cardiomyopathy.
• RCM may be idiopathic, familial, or result from various systemic
disorders, in particular, amyloidosis, sarcoidosis, carcinoid heart
disease, scleroderma and anthracycline toxicity.
• Familial RCM is often characterized by autosomal dominant
inheritance, which in some families is caused by mutations in the
troponin I gene; in others, familial RCM is associated with
conduction defects, caused by mutations in the desmin gene
(usually associated with skeletal myopathy).
• Rarely, familial disease can be associated with autosomal recessive
inheritance (such as haemochromatosis caused by mutations in the
HFE gene, or glycogen storage disease), or with X-linked inheritance
(such as Anderson–Fabry disease).

28. RCM: Aetiology
Restrictive
Cardiomyopathy
Primary Restrictive
Cardiomyopathy
Secondary Restrictive
Cardiomyopathy
Endomyocardial
Fibrosis
Loeffler’s
Cardiomyopathy
Idiopathic Restrictive
Cardiomyopathy
Infiltrative Disease Storage Disease
Amyloidosis
Sarcoidosis
Postirradiation
Therapy
Haemochromatosis
Glycogen Storage
Disease
Fabry’s Disease
Leung DY & Klein AL. In: Topol EJ, Califf RM, Isner JM, et al, eds.
Textbook of Cardiovascular Medicine. Lippincott-Raven Publishers
1998, pp 604

29. Unclassified Cardiomyopathies
• Takotsubo Stress CM is characterized by transient regional systolic dysfunction
involving the left ventricular apex and/or mid-ventricle without obstructive coronary
disease on coronary angiography.
• Patients present with an abrupt onset of angina-like chest pain, and have diffuse T-
wave inversion, sometimes preceded by ST-segment elevation and mild cardiac
enzyme elevation.
• Most reported cases occur in post-menopausal women. Symptoms are frequently
preceded by emotional or physical stress.
• LV function usually normalizes over a period of days to weeks and recurrence is
rare. The same kind of reversible myocardial dysfunction is occasionally
encountered in patients with intracranial haemorrhage or other acute cerebral
accidents (neurogenic myocardial stunning).

30. Unclassified Cardiomyopathies
Peri-partum cardiomyopathy
• Etiologies: Not so clear
• Theories:
– Myocarditis (Viral)
– Abnormal Immune response
– Genetics
– High Post-partum salt intake
Criteria for Diagnosis:
1 Development of heart failure in the last month of pregnancy
or 5 months postpartum
2 Absence of determinable cause for cardiac failure
3 Absence of heart disease before last month of pregnancy
4 LV dysfunction demonstrated on Echo
Outcome / Prognosis
Most recover normal cardiac function between 2 weeks up to six
months in majority of cases with medical therapy
Bromocriptine may have a role in management
• 4% of all cardiomyopathy
• 1:3000-4000 pregnancies
• Dilated cardiomyopathy
Risk Factors
• Age >30
• Multiparity
• African Descent
• Maternal cocaine abuse
• Long term tocolytic therapy
• Pregnancy with multiple
fetuses
• History of Pre-eclampsia or
post-partum hypertension

31. Cardiomyopathies: Clinical symptoms
• Asymptomatic incidental cardiomegaly/screening
• Heart failure
– Progressive dyspnoea on exertion
– Impaired exercise capacity
– Orthopnoea
– Paroxysmal nocturnal dyspnoea
– Peripheral oedema
• Symptoms related to arrhythmias (atrial/ventricular arrhythmias/conduction
disturbance) i.e. syncope, palpitations
• Sudden death
• Systemic Emboli can also be a complication (from a ventricular thrombus)

32. Cardiomyopathies: Investigations & findings
Diagnostic
• ECHO
• Left +/- right ventricular dilatation
• Reduced left ventricular ejection fraction
• Mitral and tricuspid regurgitation
• Left ventricular thrombus
• Cardiac MRI
Screening for aetiology / complications
• ECG
• Sinus tachycardia, left atrial abnormality, Low voltage
• Diffuse non-specific ST-T wave abnormalities
• Interventricular/AV conduction defects
• Viral screening
• Chest x-ray
• Cardiomegaly
• Interstitial/alveolar oedema (advanced cases)
• Transvenous endomyocardial biopsy

33. Cardiomyopathies: Investigations & findings
Therapeutic
• Cardiac Catheterization & Angiography
– Exclude ischaemic heart disease
– Management of acutely decompensated patient
– Elevated left & right sided filling pressures
– Reduced cardiac output

34. Cardiomyopathies: General management
• Avoid intense physical exertion, competitive sports &
dehydration
• Diuretics used with caution
• Family screening, genetic
• ICD – patients with high profile for SCD
• Evaluation and serial monitoring

35. Cardiomyopathies: General management
• Therapy as per heart failure
– ACE inhibitor, B-blocker (advanced diagnosis
spirinolactone)
• Avoid …….
– Alcohol
– Calcium Channel Blockers
– NSAID
• Biventricular pacing/AICD
• Left Ventricular Assist Device (LVAD)
• Cardiac transplantation – advanced disease
and refractory to other therapies
LVAD

36. Population & International Health – Screening
• 1st degree relatives of SCD <40 years old are referred to a heart
rhythm specialist
• Genetic testing and further investigations are available if appropriate
• In the context of sudden cardiac death:
– Family history must be established including any histories of
unexplained syncope, sudden death, muscle weakness or congenital
deafness
– Each 1st degree relative should have a history taken and undergo an
examination
• The following investigations are often undertaken:
• Minimum of an ECG and an ECHO
• Holter monitor (24 hours or longer)
• Cardio-pulmonary exercise ECG test

37. Population & International Health – Screening
• Based on results, further specialist tests are undertaken relating to
arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome
and Wolff-Parkinson-White syndrome (WPW):
• Cardiac MRI
• Ajmaline provocation test
• Adenosine provocation testing
• Electrophysiological (EP) study in Brugada syndrome
• Genetic testing - genotyping of families with long QT syndrome,
Brugada syndrome and HCM is possible allowing confirmation of
diagnosis, clarification of carrier status and even guidance of therapy.

38. Population & International Health – Screening
• Screening with respect to HCM
– Children below the age of 10 years at risk of developing a
particular disease should be screened with an ECG and
echocardiogram every 3-5 years. If there is a family history of HCM
then the period of screening should be every 6-12 months from the
age of 10 years, when the disease is at the most risk of developing
– From the age of 16 to 20 years then annual screening is advised. If
there is are signs of late-onset hypertrophic cardiomyopathy in the
family then there should be continued screening at 5 yearly
intervals after the age of 20 years.

39. MCQ 1
A 23 year old woman presents to his emergency department with a 3 day history
of dyspnoea on exertion. An ECG demonstrates that the Sokolov-Lyon voltage
criteria are met and she has a jerky pulse on examination. She has no relevant
background medical history. What is the most likely underlying diagnosis?
A. Post-Partem Cardiomyopathy.
B. Dilated Cardiomyopathy.
C. Hypertrophic Cardiomyopathy.
D. Takotsubo’s Cardiomyopathy.
E. Alcoholic Cardiomyopathy.

40. MCQ 2
A 58 year old man presents to the emergency department with increasing
dyspnoea for the past 4 months. He had been attending his general practitioner
for treatment of dyspnoea and dry cough for the past month. An ECHO in the
emergency department reveals diastolic dysfunction indicative of restrictive filling
of the left ventricle. His chest x-ray reveals established pulmonary fibrosis. What
is the most likely unifying diagnosis?
A. Radiotherapy Related Changes.
B. Anthracycline Related Changes.
C. Sarcoidosis.
D. Amyloidosis.
E. Haemochromatosis.

41. MEQ
30 year old female presented to the Emergency Department with 3 weeks
history of dyspnoea on exertion with NYHA class 3 associated with
occasional chest on exertion and feeling faint. She recently had a healthy
baby girls 8 weeks ago. Her delivery was normal with no complications.
She has no previous medical or surgical history and takes no
medications. D-Dimer was normal and she had CT pulmonary
angiography which excluded a pulmonary embolus. ECG was normal.
Echocardiography demonstrated reduced LV Ejection Fraction to <40%
with normal valves function and structures.
Q1. What is the most likely diagnosis?

42. MEQ Cont.
Q2. What other investigations may you consider for this patient?
Q3. How would manage this patient given her diagnosis?

43. MEQ Cont.
Q4. List a theoretical risk factor for development of this condition?
Q5. Given her diagnosis, prognosis and ECHO finding would you
consider an implantable defibrillator for this patient and briefly explain
your answer?

44. REFERENCES
1. ESC working group on myocardial pericardial disease
(Elliott P et al. ENJ 2007)
2. AHA Scientific Statement Contemporary Definitions and
Classification of the Cardiomyopathies Circulation 2006
3. http://circ.ahajournals.org/content/113/14/1807.full