Cardiomyopathies Flashcards
What is cardiomyopathy?
heart disease resulting from an abnormality in myocardium
What kind of abnormalities occur in cardiomyopathy?
abnormalities in cardiac wall thickness, chamber size, mechanical and/or electrical dysfunction
What is primary cardiomyopathy?
confined to heart muscle
What is secondary cardiomyopathy?
myocardial involvement as a component of systemic or multiorgan disorder
What is dilated cardiomyopathy and what happens?
progressive cardiac dilation: systolic dysfunction, hypertrophy, Enlarged, heavy, flabby, dilated heart, HEART FAILURE, Thrombi may form, Regurgitation- may be due to ventricular dilation (functional regurgitation)
x-linked dilated cardiomyopathy is usually caused by mutation in what?
dystrophin gene
In 20-50% of dilated cardiomyopathy genetically causes cases what is the mutation?
Predominantly autosomal dominant mutations encoding cytoskeletal proteins like α-cardiac actin, desmin, & nuclear lamins A/C
What mutations in the mitochondrial genome cause dilated cardiomyopathy?
Mutations in genes involved in oxidative phosphorylation & fatty acid ß-oxidation
What virus usually cause acute viral myocarditis?
Coxasackie B or echovirus usually Self-limited infection in young people
How does acute viral myocarditis lead to dilated cardiomyopathy?
Mechanism: unclear– Myocyte cell death and fibrosis– Immune mediated injury– No change with immunosuppressive drugs
Two toxins that can cause dilated cardiomyopathy?
Alcohol and doxorubicin
What does alcohol do to cause dilated cardiomyopathy?
direct toxic effect myocardium &indirect toxic effect associated with thiamine deficiency lends to beriberi heart disease
What does doxorubicin (adriamycin) cause?
Dilated cardiomyopathy and heart failure• Anthracycline toxicity is dose-dependent
When does peripartum cardiomyopathy occur?
Late in pregnancy or several weeks to months postpartum
Possible causes of peripartum cardiomyopathy?
– Pregnancy-associated hypertension– volume overload– nutritional deficiency– metabolic derangements– immunological reaction– prolactin
Dilated cardiomyopathy causes cardiomegaly, what’s that?
heart is 2-3 times normal weight & globular appearance
Are the valves normal in cardiomyopathy?
Yes, however Mitral or tricuspid regurgitation may be present due to dilation of chamber
What are a few other gross morphologies of cardiomyopathy?
• Four chamber dilatation• Variable wall thickness( normal, hypertrophy, flabby)• Mural thrombi
What does dilated cardiomyopathy look like on histology?
Histologic changes are not specific for DCM (except for iron overload –stainable) Some fibers may appear stretched or irregular; no necrosisHypertrophy and fibrosis are usual
Can iron overload cause dilated cardiomyopathy?
Yes, via Hemochromatosis & Multiple transfusions
Increased risk of ldiopathic dilated cardiomyopathy associated with what?
– MALE GENDER– BLACK RACE– HYPERTENSION– CHRONIC BETA-AGONIST USE
Clinical presentation of idiopathic dilated cardiomyopathy?
• Heart failure symptoms 75%-85%• Anginal chest pain 8%-20%• Emboli (systemic or pulmonary) 1%-4%• Syncope <1%
Prognosis of idiopathic dilated cardiomyopathy?
50% of patients die within 2 years, 25% survive longer than 5 yearsDeath due to cardiac failure, arrhythmia or thromboembolic complications
What is Arrhythmogenic Right Ventricular Cardiomyopathy?
Inherited autosomal dominant disease of cardiac muscleright ventricular failure and various rhythem disturbances ventricular tachycardia or fibrillationcan lead to sudden death
What is the morphology of Arrhythmogenic Right Ventricular Cardiomyopathy
right ventricular wall is severely thinned because of loss of myocytes, with extensive fatty infiltration and fibrosis
• Clinical– Occurs in young adults– Arrhythmias (ventricular tachycardia) – Sudden death – Right ventricular failureWhat is this?
Arrhythmogenic right ventricular cardiomyopathy/dysplasia
What is the essential feature of Arrhythmogenic right ventricularcardiomyopathy histology?
fatty infiltration
What is Hypertrophic cardiomyopathy (HCM)?
myocardial hypertrophy, poorly compliant left ventricular myocardium leads to abnormal diastolic filling
What happens to the heart wall in HCM?
Heart is thick-walled, heavy, and hypercontracting (contrast to flabby heart of DCM)
Is diastolic or systolic function affected by HCM?
Primarily diastolic dysfunction; systolic function is usually preserved intermittent left ventricular outflow obstruction
Describe ventricular hypertrophy.
– Disproportionate thickening of the septum
– subaortic region (“Banana”shape)
– No ventricular dilatation, ventricle compressed
What happens to the atrium in HCM?
Atrium enlarged due to decreased ventricular compliance
Describe the histology of HCM.
Marked hypertrophy (>40 µm, normal 15 µm)
Interstitial fibrosis
Myofiber disarray
What kinds of genetic components can HCM have?
Missense mutations in genes encoding sarcomeric proteins with Familial, Autosomal dominant, Variable expression
Which sarcomeric proteins are usually deffective?
myosin heavy chain β-MHC
myosin binding protein MYBP-C
cardiac TnT
How do defects in sarcomeric proteins affect the heart?
Defects in direct sarcomere function and transfer of energy to sarcomere
Half of HCM pt have left ventricular outflow tract obstruction what is it?
Caused in two ways:
narrowed left ventricular outflow tract due to hypertrophied interventricular septum or anterior displacement of mitral valve leaflets during systole
Mitral valve regurgitation of anterior leaflets & chordae sucked into the outflow tract during mid-late systole causing obstruction secondary to HCM is called what?
Venturi effect
Diastolic dysfunction can occur with HCM, how?
the myocardium is stiff, non-compliant
- the left ventricular diastolic pressure is elevated
- the filling of the ventricle in diastole is impaired
Due to the hypertrophy of HCM there can be supply/demand mismatch, impaired relaxation during diastole and abnormal intramyocardial arteries which can lead to what?
Myocardial ischemia in the absence significant coronary arteries athersclerosis
What arrhythmias can occur as a result of HCM?
1 Paroxysmal supraventricular arrhythmias (Occur in 30-50%)
2 Atrial fibrillation
3 Non-sustained ventricular tachycardia
4 Sustained ventricular tachycardia/ventricular fibrillation (lethal in many pt)
Over the course of a lifetime, when does HCM usually present?
Presentation after puberty
Signs and symptoms of HCM?
▫ Asymptomatic
▫ Exertional dyspnea due to limitation of cardiac output
▫ Syncope due to left ventricular outflow obstruction
▫ Sudden death in young athletes
▫ Atrial fibrillation with mural thrombus formation
Treatment for HCM?
surgical excision & ventricular relaxing drugs
Risk factors for cardiac death with HCM:
- Marked ventricular wall hypertrophy (>30mm)
- Young age at presentation (< 40 y)
- History of syncope
- History of aborted cardiac arrest
- Family history of sudden cardiac death
- Certain genetic mutations
Pharm treatments of HCM include:
Beta-blockers (first line)
Calcium-channel blockers (in combo or pt who cannot tolerate beta)
Disopyramide
Non-pharm therapy includes:
Surgical septal myectomy
Alcohol induced septal ablation (infarction of injected area)
Dual-chamber pacemaker (at RV apex)
Heart transplant
Implantable cardioverter-defibrillators can help prevent this serious complication?
Sudden cardiac death
What is restrictive cardiomyopathy?
Primary decrease in ventricular compliance,
resulting in impaired ventricular filling during
diastole
What are the causes of restrictive cardiomyopathy?
Idiopathic or Secondary to: – Post-radiation fibrosis – Amyloidosis – Sarcoidosis – Metastases – Inborn errors of metabolism (Fabry’s disease, Pompe’ s disease)
Gross anatomy description is of what disease?
– Normal ventricles (size, wall thickness)
– bi-atrial dilation
– firm myocardium
– interstitial fibrosis
Restrictive cardiomyopathy
What is the histology of Restrictive cardiomyopathy?
Patchy or diffuse interstitial fibrosis and disease specific changes
Clinical features of restrictive cardiomyopathy?
congestive heart failure with severe pulmonary and hepatic congestion
What test would you use to diagnose restrictive cardiomyopathy?
endomyocardial biopsy
Types of amyloidosis of the heart?
Senile cardiac amyloidosis: most common
Systemic AA or AL amyloidosis can also involve the heart
Causes of senile cardic amyloidosis?
– Transthyretin (prealbumin)– deposits in ventricles and atria
– > 60 yrs age; African-Amer vs. Caucasians = 4:1
– Gene mutation in 4% (isoleucine is substituted for valine), autosomal dominant familial form
What does amyloidosis of the heart do to the hemodynamics?
It varies:
– Asymptomatic
– Pressure atrophy of fibers
– Deposition in regions of conduction system leads to arrhythmias
Describe the morphology of amyloidosis of the heart.
Heart normal or
firm and rubbery with Eosinophilic
deposits of amyloid
Endomyocardial fibrosis, large mural thrombi, peripheral
eosinophilia, eosinophilic infiltrates in organs
Eosinophils release major basic protein which may
cause endomyocardial necrosis and scarring
What cardiomyopathy is this?
Loeffler endomyocarditis
Most common in first 2 years of life
Disease of children and young adults in Africafocal or diffuse fibroelastic thickening usually involving mural left ventricular endocardium
What cardiomyopathy is this?
Endocardial fibroelastosis
What are the cardiac effects of iron overload?
Heart is usually dilated, rust-brown colored, hemosiderin accumulation, fibrosis may be present
Cardiac effects of hyperthyroidism?
tachycardia, palpitations, and cardiomegaly
Cardiac effects of hypothyroidism?
CO decreased, fluid accumulation in pericardial sac, flabby enlarged dilated heart
Cardiac histological features of hypothyroidism?
myofiber swelling with loss of striations and basophilic degeneration, interstitial mucopolysaccharide-rich edema fluid
What is sarcoidosis?
Restriction
Conduction System Disease
Ventricular Arrhythmias
(Sudden Cardiac Death)
What are a few cardiotoxic drugs?
Lithium, phenothiazines, chloroquine and cocaine
What is Takotsubo cardiomyopathy and what causes it?
Sudden, intense emotional or physical stress leading to acute left ventricular dysfunction which on catecholamines
