Cardiomyopathy,myocarditis,pericarditi,tumor

Pericarditis , Cardiomyopathy,myocarditis and cardiac tumors

Dr.Vaishali KotasthaneAssistant Professor,Pathology

Lesson Plan

Pericarditis : classification-eitiology/morphology

Cardiomyopathy:Types-Dilated/Hypertrophied/Restricted

Myocarditis: causes Cardiac tumors

Pericarditis

What is pericardium?

Fibrous sac surrounding heart-dense network of collagen fibres

Serous membrane – two continuous layers separated by a small amount of fluid lubricant (10-20mls straw coloured)

Layers are called visceral and parietal Visceral is inner layer (epicardium) Parietal is continuous with diaphragm and

outer walls of great arteries

Where is it?

Surrounds the heart Continuous with the great arteries

and the diaphragm

Pericarditis

Usually secondary to disorders involving the heart, or adjacent mediastinal structures (Eg: Myocardial infarct, trauma, radiation, tumour or infections).

Rarely, may be due to systemic abnormalities (uremia, diabetes mellitus, chronic nephritis, severe anemia , autoimmune disease).

Etiology of Pericardial Diseases

Viral Infections Purulent

Pericarditis TB Mediastinal

radiation MI Cardiac surgery Trauma

Cardiac procedures Drugs and Toxins Metabolic disorders Malignancies (breast,

lung, Hodgkin’s, mesothelioma)

Collagen Vascular Disease

Idiopathic

Etiologies of Pericarditis Neoplastic-35% Immune Mediated- 23% Viral- 21% Bacterial-6% Uremia-6% TB- 4% Idiopathic-4%

Viral Pericarditis Common bugs

Cocksackie A and B Echovirus Adenovirus

Viral infections uncommon in patients presenting with pericardial effusion w/o pericarditis Exception is HIV- frequently presents with

significant effusion w/o pericarditis seen in 7 % of patients hospitalized with

effusions

Bacterial Pericarditis Staphylococcus Pneumococccus Streptococcus(rheumatic pancarditis) Haemophilus M.Tuberculosis Can occur as systemic spread or direct

extension Frequently purulent

Fungal Pericarditis Histoplasma- most common fungus

in immunocompetent patients Especially the Ohio River Valley

In immunocompromised Aspergillus Candida Coccidoides

Frequently purulent

Other Infectious Etiologies Rickettsia Ricketsii Chlamydia Psittaci Borrelia burgdorferi Treponema Pallidum Actinomycosis Mycoplasma Pneumonia Nocardia

Post MI Pericardial involvement is related to

infarct size Early stage - inflammatory etiology Late stage

Immune mediated weeks to months out Known as Post Cardiac Injury syndrome (PCIS)

or Dressler’s syndrome Rare in modern time due to reperfusion

therapies

Iatrogenic Causes Mediastinal Radiation-wide spectrum

of diseases seen Cardiac Surgeries Cardiac Procedures Traumatic

Drugs Lupus like sydromes

Procainamide Hydralazine Phenytoin INH

Penicillins- Hypersensitivity Pericarditis Chemotherapy

Doxorubicin/Daunorubicin-cardiomyopathy/pericardiopathy

Bleomycin - sclerosing agent

Toxins Asbestosis can cause pericardial

lesions Scorpion fish venom can cause

pericarditis

Metabolic Disorders Uremia-

Most common metabolic cause 6-10 % of ESRD patients not on HD can have

Pericarditis Dialysis related Pericardial Effusions (seen in

13% of patients) Severe Hypothyroidism

effusion – usually not significant rarely pericarditis

Ovarian hyperstimulation syndrome complication of gonadotropin therapy Due to fluid shifts

Malignancy Responsible for 6% of acute pericardial

disease (pericarditis and tamponade) Accounts for 15-20% of moderate to large

pleural effusions Mets - Lung, Breast, Hodgkin’s metastases Primary - Mesotheliomas and lipomas

Collagen Vascular Disease SLE- pericardial involvement in up to

50% Rheumatoid Arthritis Progressive Systemic Sclerosis MCTD Polyarteritis Giant Cell Arteritis Inflammatory Bowel Disease

Idiopathic In two large series (331 patients),

only 16 % had an identifiable cause of pericarditis

Many of these cases are presumed viral

Only 7-29% of patients have idiopathic pericardial effusions

Clinical Presentation of Pericarditis Chest Pain-

sudden onset over anterior chest sharp and pleuritic Improves by leaning forward Radiates commonly to trapezius ridges

Pericardial Friction Rub ECG – findings depend on stage 2 of 3 needed to make diagnosis +/-

effusion.

Pericarditis-summary Classification on the basis of etiological factors: 1. Acute nonspecific (idiopathic) 2. Infective : a) Bacterial b) Viral c) Other infections 3. Immunologic : a) Rheumatic fever b) Other connective tissue

disorder 4. Neoplastic 5. Metabolic : a) Uremic b) Myxedema c) Gout. 6. Traumatic (including after cardiac surgery) 7. Associated with myocardial infarction.

Pericarditis

Acute pericarditis - most often of viral origin.

Acute pericarditis - heal by resolution or by pericardial fibrosis ranging from a thick, pearly, nonadherent epicardial plaque , to thin delicate adhesion to massive adhesions.

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PERICARDITIS Morphological Classification of acute

pericarditis:SEROUS: SLE, scleroderma, tumors,

uremiaFIBRINOUS: MI (Dressler), uremia,

radiation, RF, SLE, s/p open heart surgeryPURULENT: infective, bacterialHEMORRHAGIC: Malignancy, TBCASEOUS: TBCHRONIC: (ADHESIVE, CONSTRICTIVE)

Acute pericarditis

Serous pericarditis : Usually consists of 50 to 200 ml of slowly

accumulating exudates Characteristically produced by nonbacterial

involvement, including rheumatic fever, systemic lupus erythematosus, tumours, uremia and primary viral infection (Eg. Coxsackie)

Microscopically- scant epicardial or pericardial acute and chronic inflammatory infiltrates.

Fibrinous and serofibrinous pericarditis: Most common clinical form, seen in myocardial

infarct with a pericardial friction rub. Causes-Acute MI,Dressler’s syn,uraemia,chest

radiation,RF,SLE,rheumatoid heart disease, trauma and routine cardiac surgery.

Morphology-maybe dry or yellow,thick and cloudy fluid

Loud pericardial friction rub Exudate may be completely resolved or be

organized causing adhesive pericarditis.

Bread and butter pericarditis

Purulent (suppurative) pericarditis: Due to bacteria, fungus or parasitic

infection.

Infection reaches by direct extension, by hematogenous or lymphatic route from neighbouring areas of infection e.g. Pneumonia, empyema, lung abscess, subphrenic abscess, liver abscess etc or during cardiotomy.

Most common causative organisms- Staphylococci, Streptococci, and Pneumococci.

Composed of 400 to 500 ml of a thin to creamy pus with erythematous, granular serous surfaces.

Patient presents with fever, rigor and a friction rub.

It usually organizes and may produce mediastinopericarditis or constrictive pericarditis.

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Hemorrhagic pericarditis: Composed of exudates of blood

admixed with fibrinous to suppurative effusion.

Most commonly it follows cardiac surgery or is associated with tuberculosis or malignancy.

It usually organizes with or without calcification.

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Caseous pericarditis: Due to tuberculosis (by direct

extension from neighbouring lymphnodes) or less commonly, mycotic infection.

This type most frequently, causes fibrocalcific constrictive pericarditis

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Chronic Pericarditis Healed stage of pericardial inflammation.

Seen in tuberculosis and fungal infections, which on healing may lead to damaging adhesion.

In some cases, organization merely produces thick, pearly, nonadherent epicardial plaque , to thin delicate adhesion of obscure origin.

Chronic Pericarditis Chronic pericarditis may be of the

following types:1.Adhesive pericarditis : Chronic pericarditis with adhesion

between parietal and visceral pericardium.

Mostly seen in rheumatic disease. Less commonly, may be due to infection

by pyogenic bacteria, tuberculosis etc. In some cases, the cause is unknown.

2.Adhesive mediastinopericarditis:

Pericardial sac obliterated due to adhesion between two layers of pericardium as well as between parietal pericardium and surrounding mediastinal structures, chest wall & diaphragm.

The heart thus contracts against all the surrounding attached structures leading to hypertrophy and dilation.

3.Constrictive pericarditis: Marked thickening of parietal pericardium

with less involvement of visceral pericardium causing constriction of great vessels entering and leaving heart.

Pericardial space obliterated by a dense fibrous tissue, which is often calcified.

Cardiac hypertrophy and dilation cannot occur because of the dense enclosing scar and the heart becomes smaller.

Tuberculosis is the most common cause.

Occasionally, may be due to pyogenic infection and in some, the cause is unknown but never rheumatic.

The patients of pericarditis may develop ascites and due to long standing ascites, liver & spleen are coated with fibrin.

Later, there is fibrosis of the liver (cardiac cirrhosis).

Pleura may be involved similarly. This polyserositis is known as Pick’s disease.

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CardiomyopathyCardiomyopathy

Cardiomyopathies

Cardiomyopathies are diseases characterised by cardiac dysfunction in which the main abnormality lies in the myocardium.

It is expressed as diastolic and /or systolic ventricular dysfunction.

Such abnormalities may directly affect one or both ventricles in a diffuse or multifocal fashion and in many patients produce myocardial failure or arrythmias.

Cardiomyopathies have been traditionally divided into two main categories:

(I) Primary -(idiopathic "heart muscle disease of unknown causes“)

(II) Secondary -("heart muscle diseases of known cause or associated with disorders of other systems).

I Primary cardiomyopathy: - Dilated Cardiomyopathy : Familial ; Idiopathic. Hypertrophic cardiomyopathy : Obstructive ;

Nonobstructive ; Familial ; Nonfamilial. Restrictive cardiopathy : Endomyocardial

fibrosis ; Idiopathic. II Secondary cardiomyopathy: -Inflammatory ; Metabolic ; Toxic ; Infiltrative ;

Physical agents ; Neuromuscular disorders ; Primary tumour of the myocardium ; Hematologic ; Immunologically mediated cardiomyopathy ; Miscellaneous.

Based on pathophysiology there are three major groups :

1.Dilated ; 2.Hypertrophic ; 3.Restrictive .

Dilated type - Hypertrophy & dilation of left ventricle with normal left atrium. ;

Hypertrophic type - Thick left ventricle with small cavity but dilated left atrium. ;

Restrictive type -Normal left ventricle but dilated left atrium

Functional Pattern LVEF *

Mechanisms of Heart Failure Causes

Indirect Myocardial

Dysfunction (Not Cardiomyopathy)

Dilated <40% Impairment of contractility (systolic dysfunction)

Idiopathic; alcohol; peripartum; genetic; myocarditis; hemochromatosis; chronic anemia; doxorubicin (Adriamycin); sarcoidosis

Ischemic heart disease; valvular heart disease; hypertensive heart disease; congenital heart disease

Hypertrophic

50–80% Impairment of compliance (diastolic dysfunction)

Genetic; Friedreich ataxia; storage diseases; infants of diabetic mothers

Hypertensive heart disease; aortic stenosis

Restrictive 45–90% Impairment of compliance (diastolic dysfunction)

Idiopathic; amyloidosis; radiation-induced fibrosis

Pericardial constriction

Cardiac InfectionsViruses

ChlamydiaRickettsia

BacteriaFungi

Protozoa

ToxinsAlcohol

CobaltCatecholamines

Carbon monoxideLithium

HydrocarbonsArsenic

Cyclophosphamide

Doxorubicin (Adriamycin) and daunorubicin

MetabolicHyperthroidism

Hypothyroidism

Hyperkalemia

Hypokalemia

Nutritional deficiency (protein, thiamine, other avitaminoses)

Hemochromatosis

Neuromuscular DiseaseFriedreich ataxiaMuscular dystrophy

Congenital atrophiesStorage Disorders and Other DepositionsHunter-Hurler syndrome

Glycogen storage diseaseFabry disease

Amyloidosis

Infiltrative

Leukemia

Carcinomatosis

Sarcoidosis

Radiation-induced fibrosis

ImmunologicMyocarditis (several forms)

Post-transplant rejection

Conditions asso. With heart muscle diseases

Dilated Cardiomyopathy

Characterized by slow, progressive dilation of four chambers and contractile (systolic) dysfunction;compensatory hypertrophy

Age: May occur at any age (most common 20-60 years).

Clinical presentation: Ineffective ventricular systolic contraction causes congestive heart failure, followed by embolic complications.

Etiology: Cause is unknown. May be related to the effect of

alcohol toxicity, pregnancy or genetic defect.

Heavy metal ingestion and some cytotoxic drugs give an identitical picture.

Idiopathic cases may be late sequela of viral infection.

Gross: Heart - Enlarged & flabby . Poor contractile function and stasis can lead to the formation of mural thrombi.

-An increase in total heart weight due to increase in left ventricular (LV) mass ;

-Increase in LV cavity dimension ; -Normal or reduced LV wall thickness ; -LV endocardial thickening and mural

thrombi in atria or ventricles may or may not be present.

Microscopic features: The features include permutations of the following features:

1. Myocyte nuclear enlargement (polypoidy).

2. Reduction myocyte width (attenuation) 3. Loss of myofibrils in myocytes. 4. Diffuse interstitial fibrosis. 5. Increased numbers of intertitial

lymphocytes.

Path:4 chamber

dilatationHypertrophyInterstitial Fibrosis

DCM

Hypertrophic Cardiomyopathy:

Also termed as idiopathic hypertrophic subaortic and hypertrophic obstructive cardiomyopathy.

The term hypertrophic cardiomyopathy is used clinically to denote thick walled left ventricle (LV) with a small cavity in which systolic contraction is early and discordinated, leading to outflow obstruction.

Diastolic relaxation is also impaired.

Clinical presentation: Most patients remain stationary and asymptomatic for years, but some progressively worsen with major complications.

Outflow obstruction is seldom a major problem.

Complications : Atrial fibrillation with mural thrombosis ; Embolization ; Infective endocarditis ; Congestive heart failure ; Sudden death.

Gross: In hypertrophic cardiomyopathy, the hypertrophy is not associated with ventricular dilation.

Disproportionate thickness of interventricular septum and free wall of left ventricle cause bulging of the interventricular septum into left ventricle forming “banana-like” configuration of left ventricle.

NOTE: An increase in LV mass with a thick wall and normal or reduced cavity can occur in 3 separate conditions.

1. Appropriate LV hypertrophy - there is a defined plausible cause i.e. aortic valve stenosis or hypertension.

The hypertrophy is microscopically normal. 2. Inappropriate LV hypertrophy - there is either

no cause or a cause (mild hypertension) insufficient in degree to responsible for the degree of hypertrophy.

The hypertrophy is microscopically normal. Examples are renal hypertension, athletes hearts and the hearts of infants of diabetic mother.

3. Hypertrophic cardiomyopathy - In this condition there is a histological abnormality - Myocardial disarray with bundles running in all directions and interstitial fibrosis.

65% 35%

10%

www.kanter.com/hcm

The condition is now recognised to be due to 5 different genes (heavy chain myosin , Tropinin T , myosin binding protein C , tropomyosin and preexcitation associated gene).

The 4 known genes are concerned with myofibrillary organisation within the myocyte and disorganisation leads to misshapen myocytes runnning in whorls. These genes are dominant negatives in which the mutant protein interferes with the wild type protein function.

All the genes carry a risk of sudden unexpected death.

.

Cases with a large heavy thick walled LV which may , or may not, be assymmetric are relatively easy to recognise.

About 30% of cases have a pathognomic subaortic mitral impact lesion.

A proportion of cases have normal or mild increase in LV mass and macroscopically look normal.

Microscopy to identify these cases is needed.

Restrictive Cardiomyopathy :

In this form of cardiomyopathy the abnormality of function is in LV diastolic relaxation.

The left atrial pressure rises in an effort to achieve ventricular filling.

This in turn leads to pulmonary hypertension. The LV remains normal macroscopically, while the right ventricle hypertrophies.

The commonest cause is amyloid. Primary disease of the ventricle results in

impaired ventricular filling during diastole, resulting in reduced cardiac outflow.

This may be of the following types:

Con-

Endomyocardial fibrosis: This is typically seen in children and

young adults in Africa. This is characterized by ventricular

subendocardial fibrosis, often with mural thrombus formation.

Reduced ventricular filling is due to reduced ventricular chamber volume.

Loeffler endocarditis: This is characterized by endo-myocardial fibrosis

with large mural thrombi and is found in temperate zone.

Eosinophilic infiltration is seen in multiple organs including the heart.

There may be associated peripheral eosinophilia.

Cationic proteins released from activated eosinophils in the circulation damage the endocardium.

These lesions are rapidly fatal.

Endocardial fibroelastosis: Characterized by focal-to-diffuse cartilage-like

fibroelastic thickening of the endocardium, mostly of left ventricle.

Mostly affected patients are younger than two years old.

Problems with Cardiomyopathy: In some patients arrythmias and sudden death predominate and contractile function is normal, the subjects have normal exercise tolerance in life.

Several forms exist.

- Arrhythmogenic right ventricular cardiomyopathy : (arrhythmogenic right ventricular dysplasia).

This is a familial disorder, most commonly associated with right-sided heart failure and various rhythm disturbances, particularly ventricular tachycardia and sudden death.

Morphologically, the dilated right ventricular wall is severely thinned, with extensive fatty infiltration, loss of myocytes and interstitial fibrosis.

Death occurs due to congestive heart failure, embolism of mural thrombi or fatal arrhthmias

- In other subjects there is idiopathic fibrosis in the left ventricle with a distribution and pattern unlike ischaemic disease.

It is not known whether this is acquired (? post viral) or familial.

- In the long QT syndrome (often referred to as cardio-myopathy) now known to be due to genetic defects in sodium and potassium channels in the myocyte, sudden death is common.

The heart is normal structurally (macro and micro).

Arrhythmogenic Right Ventricular Cardiomyopathy

(Arrhythmogenic Right Ventricular Dysplasia)

This is an uncommon dilated cardiomyopathy predominantly RIGHT ventricle.

So is NAXOS syndrome.

Myocarditis

Acute non-specific myocarditis usually produces rapid onset of fever, palpitations and arrythmia with cardiac failure and a high risk of sudden death.

Pericarditis may or may not be present.

Acute myocarditis is not an entity recognised by macroscopic examination alone.

MYOCARDITIS Chiefly microbial

COXACKIE A & B, CMV, HIV Trypanosoma cruzi (Chagas dis.), 80% Trichinosis Toxoplasmosis Lyme disease (5%) Diphtheria

IMMUNE: Post-viral, rheumatic, SLE, drug hypersensitivityalpha-methyl dopa, sulfas

LYMPHOCYTIC INFILTRATES are the USUAL pattern of ALL myocarditis, but eosinophils, giant cells, and even trypanosomes can be seen occasionally

OTHER Myocarditides

Adriamycin Cyclophosphamide Catecholamines (Pheochromocytomas) Amyloid, systemic or primary cardiac

Congo red stain: green birefringence with polarization

Amyloid, aging Congo red stain: green birefringence with

polarization Hemochromatosis (Prussian Blue)BOTH HYPER-, HYPO- -thyroidism

Clinico-pathological features

Self-limiting Mild pleuritic chest pain Cardiac failure Endo-myocardial biopsy-lymphocytic

infiltration and myocyte necrosis

Tumors of Heart

Primary tumors of heart rare metastatic tumors to the heart occur

in about 5% of patients dying of cancer

most common primary tumors are predominantly benign

benign tumors account for 80-90% of primary tumors

Most common primary tumors myxomas, fibromas, lipomas, papillary fibroelastomas, rhabdomyomas, angiosarcomas and other sarcomas

Myxoma

most common primary tumor of the heart in adults

90% are located in the atria, left-to-right ratio of approximately 4:1

(atrial myxomas). most are sporadic

10% have a familial cardiac myxoma syndrome (known as Carney syndrome)

autosomal dominant transmission, multiple cardiac and often extracardiac (e.g., skin) myxomas, spotty pigmentation, and endocrine overactivity

gene PRKAR1 on chromosome 17 (encoding a regulatory subunit of cAMP-dependent protein kinase A, possibly a tumor suppressor gene) is mutated in about half of known Carney complex kindreds, while most of the other kindreds have abnormalities in the locus 2p16

A:Gross:large pedunculated lesion extending into the mitral valve orifice. gelatinous appearance, B, Microscopic appearance, with abundant amorphous extracellular matrix in which are scattered collections of myxoma cells in various groupings

Rhabdomyomas

most frequent primary tumor in infants and children

discovered in the first years of life because of obstruction of a valvular orifice or cardiac chamber.

rhabdomyomas may be due to a defect in apoptosis during developmental cardiac remodeling

Morphology Gross:small, gray-white myocardial masses up to

several centimeters in diameter located on either the left or the right side of the

heart and protruding into the ventricular chambers. M/E: mixed population of cells, the most

characteristic of which are large, rounded, or polygonal cells containing numerous glycogen-laden vacuoles separated by strands of cytoplasm running from the plasma membrane to the more or less centrally located nucleus, the so-called spider cells.

These cells can be shown to have myofibrils.

Secondary/Metastatic tumors to heart most frequent tumors involving the

heart as metastases are carcinomas of the lung and breast, melanomas, leukemias, and lymphomas

Metastatic spread retrograde lymphatic extension (most

carcinomas), hematogenous seeding (many tumors), direct contiguous extension (primary carcinoma

of the lung, breast, or esophagus), or by direct contiguous venous extension (tumors of

the kidney or liver). Clinical symptoms are associated with pericardial

spread, by either a pericardial effusion that causes tamponade or by tumor bulk that is sufficient to directly restrict cardiac filling

Summary Pericarditis : Def,classification A)Eitiology: Infectitous-bacterial, viral ,fungal,parasitic Noninfectituos:immunological,systemic diseases B)Morphological-serous,fibrinous,purulent,hemorrhagic Cardiomyopathy:Types-Dilated/Hypertrophied/Restricted Myocarditis: causes Cardiac tumors:primary uncommon, Primary:Benign more common- Myxoma-adult Rhabdomyoma –infant,children Metastatic-Ca lung and breast, melanomas, leukemias,

and lymphomas