Cardiomyopathy, Pericarditis & Cardiac Tumors · DCM, morphology • in heart size (2-3 times of...
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Transcript of Cardiomyopathy, Pericarditis & Cardiac Tumors · DCM, morphology • in heart size (2-3 times of...
Objectives
• Cardiomyopathies
• Pericarditis
• Cardiac tumors
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
Cardiomyopathies, overview
3 major pathological/functional patterns
The most common (90% of the cases)
The least common
Robbins basic pathology 9th edition
These are intrinsic abnormalities in the heart muscle = cardiomyopathies
More common than cardiomyopathies
primary
Secondary (as part of systemic disorder)
Dilated cardiomyopathy (DCM) • Some causes:
-Genetic …25-50% of the cases
…over 40 genes may be mutated
…AD is the most common pattern of inheritance…mostly
cytoskeletal proteins
…X-linked…mostly dystrophin (a membrane protein that
couples ECM to cytoskeleton)
…Arrhythmogenic Right Ventricular Cardiomyopathy is also included
…AD
…can cause sudden death
…severe vent. Wall thinning & infiltration by fat, in addition to fibrosis
…the left can also be involved (but to a lesser extent)
*congenital conduction abnormalities also can be a feature of
inherited forms of DCM…some genes are needed for both
contractile myocytes & conduction fibers
Dilated cardiomyopathy (DCM) causes, cont’d -Infective myocarditis:
…Coxsackie B is the most common
-Alcohol…Ethanol and its metabolite (acetaldehyde) are toxic to cardiac
myocytes
…Beriberi heart disease may also occur
-Peripartum cardiomyopathy…multifactorial
…about 50% of the patients recover normal function
-Iron overload…the most common presentation in the heart is: DCM
DCM, morphology
• in heart size (2-3 times of normal weight)
• Flappy with dilation of all champers
• Thickness…thinner, normal or thicker
• Mural thrombi are often present
• By definition: no valvular or ischemic lesion caused this dilation
• Microscopically the changes are non-specific…except in iron overload
-Most myocytes are hypertrophic -Many are attenuated -Variable interstitial fibrosis
DCM, clinical notes • Age: 20-50 years…but can occur at any age
• Slowly progressive congestive heart failure
…ejection fraction can become less than 25% (Normal: 50-65%)
• Secondary mitral regurgitation
• Secondary arrhythmias
• Mural thrombi & resultant emboli
• 50% die within 2 years
• Trt.: Cardiac transplantation is the definitive treatment
Hypertrophic cardiomyopathy (HCM)
• Defective diastolic function
• No dilation
• Ventricular outflow obstruction in about 1/3 of the cases…see slide #13
• Hypercontractile
• Systolic function is usually preserved
• This is an intrinsic disorder (cardiomyopathy)…different from hypertrophy due to HTN or aortic stenosis (AS)…although similar functional consequences (diastolic dysfunction)
HCM, cont’d
• Mostly: AD…missense mutations in contractile proteins
• The most commonly affected: sarcomeric proteins…esp. beta myosin
heavy chain
• Some genes are also affected in DCM (e.g., beta myosin)
…but in DCM: contractility
• Morphology: the septum more than free wall… = asymmetric septal
hypertrophy
…but in 10%:
concentric hypertrophy
HCM, morphology…cont’d
Visit https://www.pinterest.com/pin/50158847 722123 3549/ for references Robbins basic pathology 9th edition
-Myocyte hypertrophy -Disarray & branching -Fibrosis
HCM, clinical notes
• Typically postpubertal growth spurt…but can occur at any age
• Impaired diastolic filling stroke volume
• In about 1/3 of the cases: outflow is also affected:
Visit http://163.178.103.176/Fisiologia/cardiovascular/Objetivo_3/Hypertrophic.htm for references
HCM, clinical notes…cont’d
• Exertional dyspnea and systolic ejection murmur
• Intramural arteries are compromised (even without atherosclerosis)
…cardiac ischemia…angina
• Arrhythmias and mural thrombi
• Infective endocarditis of mitral valve (because it became abnormal)
• Congestive heart failure
• Sudden death…especially in young athletes
Restrictive cardiomyopathy
• The ventricular wall is stiff (no compliance)…diastolic dysfunction
(impaired filling)
• Systolic (contractile) function is not affected
• Of the causes: amyloidosis, sarcoidosis, radiation-induced fibrosis
• The walls are of normal thickness or slightly thickened
• Microscopically: variable interstitial fibrosis
• Endomyocardial biopsy can reveal a specific cause
Restrictive cardiomyopathy, cont’d
**Amyloidosis:
• Extracellular deposition of proteins (insoluble β-pleated sheets)
• Can be part of systemic amyloidosis or isolated
..especially: senile cardiac amyloidosis …normal (or mutant) forms of transthyretin…a liver- synthesized circulating protein that transports thyroxine and retinol
In 4% of African Americans: a specific mutation in this protein…increased incidence of isolated cardiac amyloidosis
Restrictive cardiomyopathy, cont’d
**Endomyocardial fibrosis:
• Children and young adults in Africa and other tropical areas
• Dense diffuse fibrosis of the ventricular endocardium and subendocardium…often: tricuspid and mitral valves
• May be related to nutritional deficiencies or helminthic infections
• The most common form of restrictive cardiomyopathy worldwide
**Loeffler endomyocarditis:
• Endomyocardial fibrosis
• Formation of large mural thrombi is typical
• Eosinophilia in blood and tissue
• Major basic protein from eosinophils causes endomyocardial tissue necrosis with subsequent fibrosis
• Some patients: underlying hypereosinophilic myeloproliferative disorder…overactive PDGFR tyrosine kinase…can be controlled by tyrosine kinase inhibitors
Myocarditis • In USA: The most common are: viruses…coxsackie B
…also coxsackie A, CMV, HIV, influenza…etc.
• Chagas disease (caused by???) is the most common infective myocarditis in South America…10% die in acute attack…others: chronic CHF and arrhythmias 10-20 years
• Toxoplasma gondii (the most common vector is??)…esp. in immunocompromised
• Trichinosis…the most common helminthic cause
• Lyme disease…myocarditis occurs in 5% of the cases
• Noninfectious causes:
-SLE, polymyositis…etc.
-Drug hypersensitivity reactions… = hypersensitivity myocarditis…usually mild
• Wide spectrum of symptoms
…can progress to DCM
Pericarditis
• Can be isolated (primary…esp. viral (with myocarditis)) but in most instances: secondary (heart surgery, acute MI, pneumonia…etc.) or systemic disorder
• The most common systemic disorder is: uremia
• Can be seen in SLE, metastatic malignancies …etc.
• Can be: -self-limited
-massive…can cause cardiac tamponade
-becomes chronic fibrosing…constrictive
pericarditis
• Pericardial effusion: …serous (any cause of generalized edema)
…serosanguinous
…chylous
*if rapid (even if small amount) may cause tamponade…if slow (even if large amount) can be tolerated
Cardiac tumors
• Most common malignancy is: metastasis (in descending order: lung, lymphoma, breast, leukemia, melanoma…etc.)
• Most primary tumors are benign
• The most common primary tumor in adults: myxoma…most common site is: left atrium…in fossa ovalis (atrial septum)
• The most common primary tumor in children and infants: rhabdomyoma
…high frequency in: tuberous sclerosis (TSC1 or TSC2 loss of function…tumor suppressor genes)
• The most common primary malignant tumor: angiosarcoma
• Others: fibromas, lipomas, papillary fibroelastomas…etc.