Transcript Cardiomyopathies

Cardiomyopathies
Introduction
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Define Cardiomyopathy
Primary Cardiomyopathies
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Hypertrophic Cardiomyopathy
ARVD
Ion Channelopathies
Dilated Cardiomyopathy
Restrictive Cardiomyopathy
Myocarditis
Others
Secondary Cardiomyopathies
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Infiltrative Disease
Evolving Definition
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1957 – Cardiomyopathy used for first time
1980 WHO – “heart muscle disease of
unknown cause”
1984 WHO – “diseases of different and
often unknown etiology in which the
dominant feature is cardiomegaly and
heart failure”
1995 WHO – “disease of myocardium
associated with cardiac dysfunction”
Current Consensus Definition
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“a heterogeneous group of diseases of the
myocardium associated with mechanical
and/or electrical dysfunction that usually (but
not invariably) exhibit inappropriate ventricular
hypertrophy or dilation 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.”
Maron, BJ. Et al. Circulation. 2006; 113: 1807-1816.
That what is not…
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Disease entities NOT included in current
definition of cardiomyopathy (direct
consequence of other cardiovascular
abnormalities):
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Ischemic Heart Disease
Valvular obstruction and Insufficiency
Hypertensive Heart Disease (poorly defined)
Congenital Heart Disease
Metastatic and primary intracavitary or
intramyocardial cardiac tumors
Maron, BJ. Et al. Circulation. 2006; 113: 1807-1816.
That what IS…
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Primary Cardiomyopathies
Maron, BJ. Et al. Circulation. 2006; 113: 1807-1816.
Secondary Cardiomyopathies
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Secondary Cardiomyopathies (“specific
cardiomyopathies”)
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Infiltrative
Storage Diseases
Toxic injury, Cancer Therapy
Endomyocardial Disease
Inflammatory (Sarcoid)
Endocrinopathies
Cardiofacial
Rheumatologic Disease (Autoimmune)
Muscular Dystrophies
Nutritional/Electrolyte
Maron, BJ. Et al. Circulation. 2006; 113: 1807-1816.
Work-up/Evaluation
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History & Physical Examination
Biomarkers – May be elevated in myocarditis or acute
injury
EKG
Echocardiogram
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MRI
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Segmental vs. Global wall abnormalities, chamber size, RV
function
Distinguish ischemic from non-ischemic
Biopsy (Class IIb)
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unexplained new-onset heart failure <2 weeks with normal
size/dilated LV with hemodynamic compromise
Unexplained new-onset heart failure 2 weeks to 3 months with
dilation and new arrhythmia or block
The Genetic
Cardiomyopathies:
Hypertrophic Cardiomyopathy
HCM Facts
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Autosomal Dominant (1:500 phenotypic
expression by echo)
Most common cause of SCD in young
Common cause of HF disability in all ages
Diagnosis by 2-D Echo or MRI after clinical
suspicion (personal or family history)
Differentiate from physiologic athletic
heart
Patient Presentation
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Hypertrophy of myocardium (20-40 mm), usually in
basal to mid-ventricular septum
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Small-normal LV cavity size – Diastolic dysfunction
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Leads to subaortic obstruction (20-40% at rest, majority during
stress) – worsened with decreased preload, decreased afterload,
or increased contractility
Anterior mitral leaflet may contact the ventricular septum
resulting in “systolic anterior motion”
Mitral regurgitation
Dyspnea or Pre-Syncope/ Syncope
Increased left atrial pressure – Dyspnea with exertion
Myocardial ischemia -- Angina
Arrhythmia, Sudden Cardiac Death (1% per year)
Autonomic Dysfunction (25%)
HCM Physical Exam
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Palpable double apical impulse – Large atrial
kick, sustained LV impulse
Increased JVP with prominent “a wave”
Carotid with rapid upstroke with “bifid”
Murmur increase with maneuvers that drop
LVED volume
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Valsalva, pure vasodilators, Dehydration, decreased
venous return
Decreases with squatting
S3 and S4 gallops common
HCM Pathophysiology
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11 identified mutant genes (beta-myosin
heavy chain, myosin-binding protein C, et al.)
and >400 individual mutations
 Mutations alter sarcomeric function
 Lead to hypertrophy and fibrosis
 Myocardial diarray
 Thrombosis and obliteration of small
vessels
Other genetic diseases may mimic HCM
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Mitochondrial derangements
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Hypertrophic CM Screening
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Adult family members of HCM patients
should get surveillance echo every 5 years
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Adolescents every 12-18 months
Genetic testing only 50% accurate
Management of HCM
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Avoid dehydration
Avoid competitive athletics or stenuous activity
Pure vasodilators, high-dose diuretics, positive inotropes
should be avoided
First-line therapy – beta blockers
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Non-dihydropyridine Ca channel blockers
Septal myectomy or alcohol septal ablation for disabling
effort related symptoms
ICD for patient’s with hx of cardiac arrest or VT
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Also for patient’s with 2 of following: +Fam hx, syncope in
young, NSVT episodes, >3 cm hypertrophy, autonomic dysfxn
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A 42 y/o woman comes to the office for evaluation of progressive angina and
dyspnea on exertion that she has noticed for the past 6 months. She has no history
of cardiovascular disease, other than a longstanding murmur. She has never
smoked, has no family history of CAD, does not have DM or HTN, and has normal
Lipids. On phyical examination, BP 112/70, HR 86, with regular rhythm; JVP normal;
carotid upstorkes are brisk without bruits; and lung fields are clear. Cardiac
examination shows normal S1 and S2. An S4 is also noted. She has a grade II/VI
late-peaking systolic ejection murmur that increased with the strain phase of Valsalva
maneuver as well as when she rises from squatting to standing. The apical impulse
is bifid. The abdomen and extrmities appear normal.
Chest radiography shows mild increase in pulmonary vascularity. Heart normal size.
ECG shows LVG with deep T-wave inversions in precordial leads. Echocardiogram
shows asymmetric septal hypertrophy, with maximum septal thickness of 22 mm.
Significant systolic anterior motion of the mitral valve is noted and causes moderate
mitral regurgitation. The patient has a left ventricular outflow tract obstruction of 64
mm Hg.
Which of the following is best initial management of this patient’s condition?
A. Isosorbide mononitrate 30 mg/d
B. Lisinopril 5 mg/d
C. Metoprolol 25 mg twice a day
D. Furosemide, 40 mg twice a day
E. Sustaine-release nifedipine, 60 mg/d
The Genetic
Cardiomyopathies:
Arrythmogenic RV Dysplasia
Arrhythmogenic RV Dysplasia
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Autosomal dominant with incomplete
penetrance: 1:5000 phenotypic expression
RV predominantly involved with myocyte
loss with regional fatty of fibrofatty tissue
replacement
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LV involvement in 75% of patients
Presents with ventricular tachyarrhthmia
Most common cause of sudden death in
competitive athletes in Italy
AVRD Diagnosis
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Diagnosis based on:
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Arrhythmia, syncope, or cardiac arrest
Global or segmental chamber dilation or wall
motion abnormalities (usually in RV)
Diagnostic Testing:
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ECG (T wave inversion in V1-V3, RBBB)
Echo, Cardiac MRI, Cardiac CT, and RV
angiography
Endomyocardial biopsy
The Genetic
Cardiomyopathies:
Left Ventricular Noncompaction
LV Noncompaction
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Distinctive “spongy” appearance of LV
myocardium
Usually involves distal (apical) portion of LV
chamber
Results from arrest in normal embryogenesis in
both familial and nonfamilial forms
Diagnosed by 2D echo, MRI or LV angiography
Associated with HF, thromboemboli, arrythmia,
and sudden death
The Genetic
Cardiomyopathies:
Ion Channelopathies
Ion Channelopathies
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LQT Syndrome
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Risk for torsade des pointes, syncope, and sudden
cardiac death
Variable phenotypic expression
Jervell & Lange-Nielson syndrome
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Associated with deafness
Autosomal recessive
2 genes that code for slow potassium channel
Romano-Ward syndrome
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More common autosomal dominant
8 genes may have mutations (6 for K channels, 1 for Na
channel, 1 for ankyrin)
Ion Channelopathies
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Brugada Syndrome
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First described in 1992
Sudden cardiac death in young people
EKG with RBBB and coved ST-segment
elevation in V1-V3
If concealed can be unmasked with Class I
antiarrythmics
Linked to mutations in cardiac sodium
channel gene (LQT3)
Short QT Syndrome
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Sudden cardiac death from VT/fibrillation
Tall peaked T waves as with hyperkalemia
Ion Channelopathies
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Catecholaminergic Polymorphic Ventricular
Tachycardia
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Syncope, Sudden death, polymorphic VT
triggered by vigorous exertion or emotion
Normal resting ECG
Autosomal dominant form linked to RYR2
gene which codes for “large ryanodine
receptor protein” that regulates calcium
Ideopathic Ventricular Fibrillation
Mixed Cardiomyopathies:
Dilated Cardiomyopathy
Dilated Cardiomyopathy
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Common with prevalence of 1:2500
usually in 3rd to 4th decade with 3:1 male
to female ratio
Most common cause of heart transplant
Ventricular enlargement, systolic
dysfunction, and normal LV thickness
Diagnosis by 2D Echo
Progressive HF, arrhythmia, heart block,
thromboembolism, sudden death
DCM Causes
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Both genetic and acquired
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Infectious agents (viral, bacterial, fungal, myobacterial,
parastitic)
Toxins (alcohol, chemo/doxorubicin)
Autoimmune
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Post-viral “Barney Clark’s Disease
Dermatomyositis/Connective Tissue Disease
Endocrinopathies (Pheo, Acromegally)
Neuromuscular disease (muscular dystrophy)
Infiltrative Diseases (hemochromatosis, sarcoid)
Mitochondrial defects
Metabolic/Nutritional
Familial (20-35% of cases)
Mixed Cardiomyopathies:
Restrictive Cardiomyopathy
Restrictive Cardiomyopathy
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Increased stiffness of myocardium
Impaired ventricular filling
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Normal or reduced diastolic volume
Normal or near-normal systolic function
Right-sided HF symptoms (JVD, edema, ascites)
more than left-sided symptoms
Pathogenesis of RCM
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Pressure in walls of ventricle rise precipitously
with minimal increase in volume
Early diastolic filling of
ventricle
 Deep and early decline in
ventricular pressure
 Rapid rise to plateau in
early diastole (square
root)
Restrictive CM vs. Constrictive
Pericarditis
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Must distinguish from
constrictive pericarditis
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Kussmaul’s (CP)
Rapid y-descent more
common (CP)
LVEDP usually equal to
RVEDP (CP)
Increased RV systolic velocity
and decreased LV systolic
velocity with inspiration (CP)
Etiologies
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Idiopathic RCM/ Primary RCM
Amyloidosis
Infiltrative/Storage Disease
Endomyocardial Fibrosis/ Eosinophilic
Disease
Primary Restrictive
Cardiomyopathy
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Rare
Either sporadic and familial forms
Mild to mod increase in cardiac weight with
patchy interstitial fibrosis
Normal or decreased volume of ventricles,
normal thickness but impaired ventricular filling
with restrictive physiology
Normal systolic function
Biatrial enlargement with thrombi in atrial
appendages common (1/3 of patients)
May require permanent pacing
Treatment of Restrictive Disease
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Diuretics with caution (preload
dependence)
Treat atrial fibrillation (rhythm or rate)
Chronotropic agents may worsen failure -Fixed stroke volume
Pacemaker
Oral anticoagulation
Heart transplantation
Acquired
Cardiomyopathies:
Myocarditis
Myocarditis
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Diagnosed as DCM over weeks to months
Slight male predominance
Symptoms range from fatigue, DOE,
palpitations, precordial chest pain and syncope
Often associated with viral prodrome
Commonly associated with myopericarditis
Most resolve with few short-term sequelae over
one to six months
Important cause of sudden death
Cooper, LT. NEJM. 2009; 360:1526-1538.
Myocarditis Infectious Causes
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Viral & Post-viral
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Borrelia burgdorferi (Lyme)
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Transient/permanent heart block or arryhthmia
Coinfection with ehrlichia or babesia
Trypanosoma cruzi (South America)
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Coxsackievirus B – 1950’s through 1990’s
Adenovirus – late 1990’s
Parvovirus B19 & other viruses – past 5 years
Hepatitis C
Less commonly: Epstein-Barr virus, CMV, HHV-6
With RBBB or LAFB (arryhthmia or heart block in 10-20%)
Left ventricular apical aneurysm, diffuse or regional
HIV – 50% or more of HIV patients on autopsy
Cooper, LT. NEJM. 2009; 360:1526-1538.
Myocarditis Variants
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Hypersensitivity Myocarditis -- Rash, fever, eosinophilia
after medications -- Anticonvulsants, antibiotics,
antipsychotics
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Giant-cell myocarditis -- DCM with thymoma,
autoimmune disorder, VT, or heart block
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Multinucleated giant cells and eosinophils
High need for Cardiac Transplant
Sarcoid myocarditis
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Also seen with Churg-Strauss, Loffler’s endomyocardial fibrosis,
cancer and parasitic infections
May see valvular fibrosis, CHF, and endocardial thrombi
May need treatment with corticosteroids
Evidence of Granuloma formation
Acute Rheumatic Fever
Cooper, LT. NEJM. 2009; 360:1526-1538.
Cooper, LT. NEJM. 2009; 360:1526-1538.
Myocarditis Treatment
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Myocarditis Treatment Trial showed no
benefit to prednisolone plus cyclosporine
or azathioprine vs. placebo for biopsyproven lymphocytic myocarditis.
IMAC (Immune Modulation for Acute
Cardiomyopathy) showed no benefit of
IVIG over usual care in LV fxn
Murphy, JG, & Lloyd, MA. Mayo Clinic Concise Textbook, 3rd Ed. 2007.
Acquired
Cardiomyopathies:
Others
Tako-Tsubo Cardiomyopathy
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Acute but rapidly reversible LV systolic
dysfunction
No atherosclerotic CAD
Triggered by profound psychological stress
Typically seen in older women
“apical ballooning” with basal LV
hypercontractile
Peripartum Cardiomyopathy
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Rare
Dilated Cardiomyopathy with impaired LV
function
Seen in 3rd trimester or first 5 months
postpartum
More frequently in obese, multiparous
women >30, with preeclampsia
50% with complete recovery in 6 months
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A 35 y/o woman who is 39 weeks pregnant presents with
progressive dyspnea. She was previously asymptomatic and has no
history of cardiovascular disease. This pregnancy is her first.
Physical examination shows a jugular venous pressure of 13 cm
H20, a diffuse apical impulse, and an apical systolic murmur. S3
and S4 are noted at the apex. Crackles are noted in both lungs. An
electrocardiogram shows sinus tachycardia, but is otherwise normal.
Base on this patient’s findings, which of the following is the most
likely diagnosis?
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A. Severe aortic valve stenosis
B. Severe tricuspid valve regurgitation
C. Atrial Septal Defect
D. Peripartum cardiomyopathy
E. Pulmonary embolism
Others
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Tachycardia Induced Cardiomyopathy
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Follows prolonged periods of SVT or VT
May mimic idiopathic DCM
Systolic function improves without impairment
after tachycardia treated
Alcohol induced dilated cardiomyopathy
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Reversible on cessation of alcohol intake
Secondary
Cardiomyopathies:
Infiltrative and Storage Diseases
Amyloid
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Usually presents with hypertrophy,
angina, and “restrictive physiology”
(associated with 55% mortality)
May see thrombi in LAA
Myocardial tissue damaged and replaced
with infiltrative interstitial deposits
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Conduction abnormalities
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“Scintillating granular sparkling”
Normal to Low voltage EKG
Etiologies
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Primary– Caused by deposition of
immunoglobulin light chains from plasma
cells, as in multiple myeloma
Secondary – less commonly involving
heart; result of inflammatory or rheumatic
disease
Familial
Other Infiltrative CMs
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Usually present as Restrictive
Cardiomyopathies
In wall, valves, or coronary arteries
Gaucher Disease – Glucocerebroside
Hurler’s Disease -- Mucopolysaccharide
Hunter’s Disease -- Mucopolysaccharide
Storage Diseases
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Hemochromatosis
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Walls not thickened
Improvement in function with treatment
Fabry-Anderson Disease
Glycogen storage disease (Pompe, type II)
Niemann-Pick disease
Secondary
Cardiomyopathies:
Toxins
Toxicity
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Drugs
Alcohol
Heavy metals
Chemical Agents
Antracyclines: Doxorubicin (adriamycin),
danuorubicin
Cyclophosphamide
Radiation
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38 y/o female undergoing chemotherapy for Hodgkin's lymphoma presents
with new-onset shortness of breath, orthopnea, and lower extremity
edema. She has completed three courses of chemotherapy including
doxorubicin to total dose of 250 mg/m2. Her prechemotherapy
echocardiogram was normal. She had no significant medical history until
diagnosis of Hodgkin’s lymphoma. Her family history is unremarkable. She
has no history of alcohol or smoking.
Her blood pressure is 110/60 and her HR is 88 bpm. She has JVP of 14 cm
with bibasilar rales. She has a regular rhythm, a 3/6 holosystolic murmur
at apex, and an S3. She has 2+ pitting lower extremity edema. Laboratory
data includes a hemoglobin of 11.1 g/dL, sodium 142 mg/dL, potassium 4.2
mg/dL, glucose 80 mg/dL, and creatinine 1.1 mg/dL. Her chest radiograph
shows cardiomegaly with pulmonary vascular redistribution and a small
bilateral pleural effusion. Electrocardiogram shows normal sinus rhythm,
poor R wave progression , and nonspecific ST and T wave changes. Repeat
echocardiogram now shows a LVEF of 25% with moderate MR.
What do you recommend to her oncologist?
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A. Continue current regimen of chemotherapy
B. Continue current regimen of chemotherpy but add ACE inhibitor
C. Continue current regimen of chemotherapy but add ACE inhibitor and betablocker
D. Change to nonanthracycline chemotherapy regimen
E. Discontinue all chemotherapy.
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A 35 y/o man who underwent closure of an ASD at age 5 years was
asymptomatic and physically active until 3 months ago, when he began to
have exertional dyspnea and fatigue. He smokes one pack of cigarettes
daily and drinks a six-pack of beer daily. He is a bricklayer and had to stop
working for the last 2 weeks. He takes no medications.
On physical examination, BP is 105/80, HR 100 bpm with occasional extra
systole. JVP is 11 cm H2o. PMI is displaced. The patient has a soft S1, a
split S2, and a grade 2/6 apical holosystolic murmur. The abdomen is
distended, the liver is palpable 1 cm below the right costal margin, and 2+
pedal edema is noted. Lab tests show a total serum cholesterol of 180
mg/dL, serum TSH 2.5 microunits/mL, BUN 32 mg/DL, creatinine of 1.3
mg/dL, Alk PHos 220 U/L, AST of 60 U/L, ALT of 75 U/L, serum filirubin of
1.2 mg/dL. Electrocardiogram shows nondiagnostic ST changes, with
occasional PVC. Gated PET scan shows an EF of 34% with global
hypokinesia.
Which is the most likely cause of patient’s heart failure?
A. ASD patch dehiscence
B. Late heart failure as result of repair of ASD
C. Alcohol consumption
D. Familial dilated cardiomyopthy
E. Coronary artery disease
Secondary
Cardiomyopathies:
Inflammatory/Endomyocardial
Endomyocardial
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Hypereosinophilic syndrome (Loeffler’s endocarditis)
Endomyocardial fibrosis
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Severe prolonged eosinophilia leads to infiltration of
myocardium
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Found in equatorial Africa
Right or left cardiac failure, sudden death uncommon
Decreased myocardial compliance
Degranulation of eosinophils leads to myocardial damage
Fibrosis, thrombus formation, obliteration of ventricular
cavity, valve abnormalities
Treat with steroids or cytotoxic agents
Inflammatory (granulomatous)
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Sarcoidosis
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Initially diastolic then systolic dysfunction
Regional wall motion abnormalities
Sudden death due to conduction system
abnormalities/blocks
Leukemia
Autoimmune
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Systemic Lupus Erythematosis
Dermatomyositis
Rheumatoid arthritis
Scleroderma
Polyarteritis nodosa
Secondary
Cardiomyopathies:
Others
Endocrinopathies
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DM
Hyperthyroidism
Hypothyroidism
Hyperparathyroidsim
Adrenal cortical insuffiency
Pheochromocytoma
Acromegaly
Neuromuscular Disorders
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Friedreich’s ataxia
Duchenne-Becker muscular dystrophy
Emery-Dreifuss muscular dystrophy
Myotonic dystrophy
Neurofibromatosis
Tuberous sclerosis
Noonan Syndrome -- Cardiofacial
Nutritional/Electrolytes
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Beriberi (thiamine)
Pallagra (niacin)
Scurvy (Vit C)
Selenium
Carnitine
Kwashiorkor
Electrolyte imbalances (K, Mg)
Conclusions
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Current classification of Cardiomyopathies
include both Primary and Secondary
Causes
Hypertrophic Cardiomyopathy, known for
triad of dyspnea, pre-syncope, and angina
is genetic disorder seen in young athletes
associated with sudden cardiac death
AVRD is pathologic condition associated
with VT and RV chamber fatty infiltration
Conclusions
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LQTS and Brugada Syndrome are Ion Channel
Disorders associated with sudden cardiac death
in the young
75% of Dilated Cardiomyopathies from
secondary causes, commonly associated with
alcohol use and hypertension
Restrictive Cardiomyopathies are associated with
elevated diastolic pressures (square root sign)
and impaired diastolic filling
Conclusions
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Common infectious etiologies of Myocarditis
have evolved from Coxsackievirus to Parvovirus
B19
Tako-Tsubo Cardiomyopathy is a rapidly
reversible cause of LV dysfunction associated
with emotional stress
Peri-partum Cardiomyopathy, usually presenting
as a dilated cardiomyopathy, can be seen from
the 3rd trimester up to 5 weeks post-partum
Conclusions
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Amyloid Cardiomyopathy presents as a
hypertrophic and restrictive cardiomyopathy,
angina, and is associated with a high mortality
Hemochromotosis and Alcohol Toxicity are
reversible forms of secondary cardiomyopathies
The antracyclines Doxorubicin (adriamycin) and
danuorubicin are associated with cardiac toxicity
References
• Murphy, JG, & Lloyd, MA. Mayo Clinic
Concise Textbook, 3rd Ed. 2007.
• Cooper, LT. NEJM. 2009; 360:1526-1538.
• Maron, BJ. Et al. Circulation. 2006; 113:
1807-1816.
• Libby, et al. Braunwald’s Heart Disease,
Eighth Ed. 2008.
Questions?