Cardiomyopathy, Pericarditis & Cardiac Tumors

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

Functional/Pathological patterns of cardiomyopathies

Robbins basic pathology 9th edition

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.