Cardiomyopathies Flashcards
Clinical presentation of dilated cardiomyopathy
Age 20-50
- Slowly progressive signs and symptoms of CHF: dyspnea, fatigability, poor exertional capacity
- Ejection fraction is less than 25% at the end
- Secondary mitral regurgitation and abnormal rhythms are common
- Death results from cardiac failure or arrhythmia
- Transplant a good option
Pathogenesis of dilated cardiomyopathy
- Progressive cardiac dilation and contractile dysfunction usually with hypertrophy
- Heart becomes dilated and poorly contractile
- Genetic influences: familial. TTN (titin). Most are AD. Genes that encode the cytoskeleton, sarcolemma and nuclear envelope. Mitochondrial defects are seen in the pediatric version. X-linked occurs in puberty (dystrophin) these also have skeletal muscle issues
Contributing factors to dilated cardiomyopathy
- Myocarditis: progression from myocarditis to DCM is possible. Coxsackie B may cause this
- Alcohol abuse: one of the major causes
- Childbirth: peripartum cardiomyopathy. Late in pregnancy or immediately after. HTN, volume overload, nutritional deficiency, or metabolic derangement
- Iron overload: hereditary hemochromatosis may be related
- Suprephysiologic stress: tachycardia, hyperthyroidism, excess catecholamines, pheos,
Morphology of dilated cardiomyopathy
- Enlarged, heavy, flabby heart
- Mural thrombi are common
- No primary valvular abnormalities
- Coronary arteries are free of significant narrowing
- Histologic abnormalities are nonspecific
- The cells are hypertrophied with enlarged nuclei
- Interstitial and endocardial fibrosis and small subendocardial scars are present
Takotsubo cardiomyopathy
left ventricular contractile dysfunction following extreme psychological stress. Contraction band necrosis occurs causing a ballooning of the heart
Arrhythmogenic Right Ventricular Cardiomyopathy
Right ventricular failure and rhythm disturbances - ventricular tachycardia or fibrillation with sudden death
Left sided involvement with left sided heart failure
Right ventricular wall severely thinned due to loss of myocytes, extensive fatty infiltration and fibrosis
Not inflammatory cardiomyopathy
Classical ARVC: AD inheritance with variable penetrance
Defective cell adhesion proteins in desmosomes linking adjacent cardiac myocytes.
Naxos syndrome
characterized by ARVC and hyperkeratosis of plantar palmar skin surfaces specifically associated with mutations in the gene encoding the desmosome-associated protein plakoglobin
Clinical presentation of Hypertrophic Cardiomyopathy
- Reduced stroke volume due to impaired diastolic filling from reduced chamber size and compliance
- Exertional dyspnea from increased pulmonary venous pressure
- Harsh systolic ejection murmur
- Focal MI may occur in the left ventricle
- Problems are: A fib, mural thrombus, stroke, intractable cardiac failure, ventricle arrhythmias, and sudden death
- *Most common cause of sudden death in young athletes
- B blockers may help
- Surgical excision of the septum and catheter based infarction may help to reduce septum size
Pathogenesis of hypertrophic cardiomyopathy
- Clinically heterogenous, genetic disorder with myocardial hypertrophy, poorly compliant left ventricular myocardium, and intermittent ventricular outflow obstruction
- Heart is heavy, thick-walled, and hypercontracting
- Diastolic dysfunction due to lack of filling
- AD disease with variable penetrance
- Most common mutation is in B-myosin heavy chain (B-MHC)
- Also in TnT, a-tropomyosin, and MYBP-C
- May also arise from defective energy transfer from the mitochondria to the sarcomere
- Interstitial fibrosis occurs secondary to this
Morphology of hypertrophic cardiomyopathy
- Massive myocardial hypertrophy without ventricular dilation
- Asymmetric septal hypertrophy: disproportionate thickening of the ventricular septum causing the ventricle to become banana shaped
- Fibrous plaque develops from the mitral leaflet contacting the septum during ventricular systole
- Histo: myocyte hypertrophy, haphazard disarray of bundles of myocytes, (myofiber disarray), fibrosis
Pathogenesis of restrictive cardiomyopathy
Primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole
-Can be caused by radiation fibrosis, amyloidosis, sarcoidosis, metastatic tumors, or the deposition of metabolites
Morphology of Restrictive cardiomyopathy
- Morphologic features are not distinctive
- Ventricles approximately normal sized and the cavities aren’t dilated
- Myocardium is firm and noncompliant
- patchy or diffuse interstitial fibrosis
- Important subgroup is amyloidosis
Endomyocardial fibrosis incidence
Children and young adults
Africa and other tropical locations
Pathogenesis of endomyocardial fibrosis
Ventricular mural thrombi sometimes develop
-Etiology unknown
Morphology of endomyocardial fibrosis
Fibrosis of the ventricular endocardium and subendocardium involving the tricuspid and mitral valves
-Diminishes the volume and compliance of affected chambers
Clinical presentation of Loeffler endomyocarditis
- Also have a peripheral eosinophilia and eosinophilic infiltrates in multiple organs
- Treatment with imatinib can help
- Rapidly fatal
Pathogenesis of Loeffler endomyocarditis
- Endomyocardial fibrosis with large mural thrombi
- MBP causes the scarring of the tissue and thrombi of the tissue
- Many have myeloproliferative disorders
- Fusion genes that constituitively activate PDGFR tyrosine kinases
Clinical presentation of endocardial fibroelastosis
first 2 years of life
May cause rapid and progressive cardiac decompensation and death
Pathogenesis of endocardial fibroelastosis
- May have aortic valve obstruction
- May be from a viral infection or from tafazzin gene mutation
Morphology of endocardial fibroelastosis
Fibroelastic thickening that involves the left ventricular endocardium
Clinical presentation of myocarditis
- Broad clinical presentation
- Some patients can have an asymptomatic course with a complete recovery
- Others can have a precipitous onset of heart failure of arrhythmias
- Usual symptoms: fatigue, dyspnea, palpitations, precordial discomfort and fever
Pathogenesis of myocarditis
- Infectious organisms or a primary inflammatory process cause myocardial injury
- Most common is a viral infection from Coxsackie viruses A and B. CMV, HIV and the flu can also
- Chagas disease: Trypanosoma cruzi in South America can have a myocardial involvement. Causes myocardial insufficiency in 10 to 20 years
- Trichonosis is the most common helminthic etiology
- Lymes disease
- also have immunologic and idiopathic causes of myocarditis
Morphology of myocarditis
- Heart appears normal or dilated, mottled and there is possibility of mural thrombi
- Diffuse, mononuclear, lymphocytic infiltrate is the most common
- biopsies are diagnostic in some cases, but can be negative
- Inflammatory lesions either resolve or cause fibrosis
Hypersensitivity myocarditis
interstitial infiltrates that are perivascular
Giant cell myocarditis
widespread inflammatory cellular infiltrate with multinuclear giant cells with a poor prognosis
Chagas myocarditis
parasitization of scattered myofibers with a mixed inflammatory infiltrate
Clinical presentation of cardiac amyloidosis
Over 70 or with systemic amyloidosis
- Can be asymptomatic, dilation, arrhythmia, mimic ischemic or valvular disease
- Depends on the location of the deposits
Restrictive cardiomyopathy
Pathogenesis of cardiac amyloidosis
B-pleated sheets in the heart due to systemic disease or restricted to the heart (senile)
- Senile: has a good prognosis. Deposits are of transthyretin (protein that transports thyroxine and retinol binding protein)
- Some African Americans have a mutation in this protein that causes an AD version of this
Morphology of cardiac amyloidosis
- Heart varies in consistency from normal to firm and rubbery
- Small semitranslucent nodules resembling drips of wax may be seen
- Hyaline eosinophilic deposits of amyloid may be found in the interstitium, conduction tissue, valves, endocardium, pericardium, and small intramural coronary arteries
- Stained w/ congo red and show apple-green birefringence
