Pathology of the Heart

By:

K .Mozaffari, MD, AP, CP

Topics

Congestive heart failure Ischemic heart disease Hypertensive heart disease Cor pulmonale Valvular heart disease Primary myocardial disease Congenital heart disease Pericardial disease Cardiac tumors

CONGESTIVE HEART FAILURE( CHF)

Inadequate output, forward failure Venous congestion, backward failure Left ,right or all chambers involved Adaptive changes: 1-Catecholamines 2-Hypertrophy & dilation ischemic injury 3-2ndary hyperaldosteronism

Consequences

Decompensation Venous congestion Pulmonary edema peripheral edema

MORPHOLOGY

Heart :dilated chambers Lungs :boggy & congested with frothy

fluid

septal widening

pale pink fluid

hemorrhages & heart failure cells

fibrosis, hemosiderin,brown induration

MORPHOLOGY

Edema of soft tissues Fluid in body cavities Liver:nutmeg appearance

centrilobular hemorrhagic necrosis

cirrhosis

Clinical features

Dyspnea Orthopnea,PND Venous congestion,edema Embolism Effusions Cyanosis,acidosis Ventricular arrhythmias

Ischemic heart disease

Angina pectoris Acute MI Sudden cardiac death Chronic IHD with CHF

Epidemiology

Any age, peak (60 in men,70 in women) Factors: HTN, DM, smoking, high LDL,

genetics Regular exercise

Pathogenesis

Critical stenosis:75% Acute plaque change Coronary artery thrombosis Coronary artery vasospasm

Acute plaque change

Fissuring, hemorrhage, rupture Disrupted plaque:

Necrotic core & lipid

Thin fibrous cap

Rich in T cells & macrophages

Coronary artery thrombosis

Plaque rupture Platelet aggregation Thrombus formation Embolization

Coronary artery vasospasm

Tx-A2 Endothelial dysfunction Increased adrenergic activity Smoking

Angina pectoris

Typical (stable): episodic pain to left arm

75% narrowing

Relieved by rest or TNG Unstable : preinfarction

increased frequency of pain Prinzmetal: at rest or sleep

spasm

Myocardial Infarction

1.5 million / yr in the U.S 500.000 deaths Men 4-5 times compared to women Risk factors the same as atherosclerosis

Pathogenesis

Necrosis begins 20-30 min after occlusion Subendocardial area more vulnerable Full size in 3-6 hrs Location of MI: site & anatomy of vessels

involved (LAD,RCA) Size of MI: proximal lesions ,larger infarcts

collateral vessels limit the size

MORPHOLOGY

LAD 40-50%:anteroapical RCA 30-40%:posterior LV wall & septum LCX15-20% :lateral LV wall Transmural MI Subendocardial MI, inner third Isolated RV or atrial infarction,rare

No gross changes before 12 hrs 18-24 hrs:slight pallor ,mottling 12-18 hrs:coagulation necrosis Wavy fiber change at periphery 18-24 hrs:PMNs,peak on 3rd day Contraction band at periphery with

hemorrhage due to reperfusion Myocytolysis,subendocardial cells with

influx of water(vacuolated)

4th-7th day: pale center, hyperemic border Macrophages, fibroblasts,capillaries migrate to

center 10th day: yellow,soft,sunken necrosis

Red-purple periphery

Granulation tissue & phagocytosis continue for weeks

4th wk: resorbed necrosis

less vascularity, more collagen 8th wk: Dense scar

thin,firm gray healed infarct

Recent MI

1 day old MI

Necrosis Wavy fiber PMNs

3-4 day old

Dense PMNs

Necrosis Hemorrhage Contraction band

7-10 days

Complete

phagocytosis

Granulation tissue

Healed MI

Scar tissue

Complications of MI

Papillary muscle dysfunction & rupture External rupture of infarct Rupture of septum Mural thrombi Acute pericarditis Ventricular aneurysms

Papillary muscle dysfunction & rupture

About 3 days after MI

LV failure

External rupture of infarct

Tamponade Between day 4-7

Rupture of septum

Left-to-right shunt

CHF

Mural thrombi

Emboli to brain

Acute pericarditis

Within 2-4 days

May cause effusion

Ventricular aneurysms

Thin-walled,fibrous outpouching

Emboli CHF Papillary muscle

dysfunction arrhythmias

Clinical features Chest pain:neck,jaw,epigastrium,left arm Rapid pulse,Diaphoresis & Dyspnea Pulmonary congestion & edema Cardiogenic shock ,if 40% of LV involved “Silent MI” in DM, HTN, elderly pts ECG:Q waves,ST abnormality,T wave

inversion

Lab markers

1-Total CK : sensitive, but not specific

CK-MB: 2-4 hrs rise, 18 hrs peak

MI excluded if no CK rise in first 2 days 2-cTnI: more specific than CK-MB

Troponin remains elevated for 4-7 days 3-LD: used in the past

Chronic Ischemic Heart Disease

Ischemic cardiomyopathy Progressive heart failure episodes of angina or MI Clinically similar to dilated CMP Severe coronary atherosclerosis Dilated chambers, fibrosis, hypertrophy Wall thickness may be normal Myocytolysis (vacuolated sarcoplasm)

Sudden cardiac death

Death within 24 hrs The most common cause is IHD VF is the most common cause Acute plaque rupture, thrombosis,vasospasm

Causes of sudden cardiac death

Coronary artery diseases Myocardial diseases Valvular diseases Conduction system abnormalities

Hypertensive heart disease

LVH(AS or IHSS must be excluded) Pressure overload Increased metabolic needs Predisposed atherosclerosis IHD,CHF,MI,arrhythmias

Morphology

Concentric hypertrophy Free wall >2cm Heart >450 g Enlarged hyperchromatic rectangular

“box-car” nuclei Fibrosis Infarcts

Cor pulmonale

Pulmonary heart disease

Acute (emboli)

>50% of vascular bed

Chronic

COPD RVH

Valvular heart disease

Rheumatic fever & heart disease Calcific aortic stenosis. Mitral valve prolapse Nonbacterial thrombotic Endocarditis Libman-sacks Endocarditis Infective Endocarditis Prosthetic cardiac valves

Rheumatic fever & heart disease

Clinical features 10 d-6 wk after pharyngitis Genetic susceptibilitiy Peak 5-15 yrs Streptolysin O, DNAse B Streptozyme test Migratory polyarthritis Pericardial effusion, tachycardia, CHF AF in MS Emboli endocarditis

Morphology

Acute rheumatic fever:

synovium,joints,skin,heart Fibrinoid necrosis Mixed inflammation Granuloma Fibrosis

Acute rheumatic carditis

Pancarditis Aschoff bodies Anitschkow cells Diffuse interstitial infiltrates Fibrinous pericarditis Serous or serosanguineous effusion Verrucous endocarditis

Aschoff body

Verrucous endocarditis

Chronic rheumatic heart disease

Mitral valve 95% Aortic & mitral valves 25% Right-sided valvular disease,uncommon Stenosis and/or regurgitation Heart failure Infective endocarditis

Chronic rheumatic mitral valvulitis Fish mouth Fused cords More in Females LA thrombi Passive lung

congestion Regurgitation

less frequent

Chronic aortic valvulitis

More in males Always with mitral

valvulitis AS lesds to

LVH,CHF Fibrosis may cause

AR

Other organs in rheumatic disease

Arthritis: large joints , self-limited Pulmonary: chronic inflammation Subcutaneous nodules (Aschoff body) Erythema marginatum (maculopapular)

Time for a quiz !

1

What is a heart failure cell?

Alveolar macrophage filled with hemosiderin

2

Nutmeg –like appearance is seen on the cut surface of which organ?

Centrilobular hemorrhagic necrosis of hepatocytes in CHF

3

Silent MI is seen in which of the following?

1-diabetes mellitus 2-hypertensive patients 3-elderly patients 4-all of the above

4

Which enzyme is more specific for myocardial injury?

Total CK CK-MB Troponin I LD

5

Anitschkow cells are seen in……….

Acute rheumatic carditis

6

Fish mouth deformity is seen in …….

Mitral stenosis

7

Erythema marginatum is seen in………

It is a maculopapular rash in acute rheumatic fever

8

Which coronary artery is more likely to sustain an infarction?

Left anterior descending coronary artery Right coronary artery Left circumflex coronary artery

9

Which morphological finding appears later in the course of an MI?

Coagulation necrosis Wavy fiber change PMN infiltration Granulation tissue

10

What is your diagnosis?

Cor pulmonale

Have a good day !

Calcific aortic stenosis

Degeneration due to aging

Sclerosis & calcification Angina,syncope,CHF Symptoms occur 10-20

yrs earlier in bicuspid valves

Mitral valve prolapse

The most common cause of isolated MR 3-5% of general population More in females, 20-40 yrs of age Loose ground substance, floppy valve Also in marfan syndrome No symptoms or palpitation, fatigue, atypical

chest pain Valve rupture, endocarditis,sudden death, LA thrombi

Nonbacterial thrombotic Endocarditis (NBTE) Small, sterile, friable

(fibrin & platelets) Aortic > Mitral valve Hypercoagulable state ( DVT) Adenocarcinoma in 50 % Marantic endocarditis Free from inflammation

or fibrosis After healing: lambl

excrescences Emboli to brain or IE

Libman-sacks Endocarditis

Sterile In SLE patients On mitral or tricuspid

valves No predilection for

closure lines

Infective Endocarditis

Vegetations on Valve or mural endocardium Acute: little host response Subacute: abnormal valves

local response

granulation tissue

Vegetations on Valve or mural endocardium Acute: little host response Subacute: abnormal valves

local response

granulation tissue

Etiology & Pathogenesis

Bacteremia:

procedures, urinary or intravascular catheters

Tooth brushing

NBTE

IVDA (right-sided valves)

Prosthetic valves (10-20% of cases)

Cardiac abnormality:

( calcific AS, VSD, RHD , MVP )

Clinical features

High fevers, chills, septicemia Low-grade fever, malaise ,weight loss Changing murmurs Splenomegaly, clubbing of digits Emboli: infarcts, mycotic aneurysms,

petechiae GN (Immune complex mediated )

Microorganisms in IENative valve:

S.Viridans

(50-60%)

S.Aureus

(10-20%)

Enterococci & HACEK (oral commensal)

Prosthetic valve:

Staph

epidermidis

G¯ bacilli Fungi

IVDA: S.aureus G¯ bacilli Fungi & Strep

Acute Endocarditis

Valve destruction Ring abscess Emboli Abscess at sites of

emboli

Organisms Fibrin Blood cells

Subacute Endocarditis

Firmer vegetations Less valve destruction Granulation tissue at base of vegetation Fibrosis,calcification Systemic emboli ,less likely to undergo

suppuration

Prosthetic cardiac valves

Bioprosthetic (porcine,bovine,human) mechanical

complications

Stiffening, calcification, perforation Thrombi Infective endocarditis Paravalvular leaks Hemolysis

Primary myocardial disease

Myocarditis Cardiomyopathies

Myocarditis

Infections Immune-mediated

unknown

Viral,chlamydial,

Rickettsial,

bacterial,

Fungi,protozoal,

helminthic

Postviral,

Rheumatic,

SLE,

Drug-induced,

Transplant rejection

Sarcoidosis

Giant cell

myocarditis

Clinical features

Coxackieviruses,the most common cause

Asymptomatic to severe CHF Sudden death Dilated CMP

Morphology

Flabby,pale myocardium Mottled by hemorrhage Abscess in bacterial cases CMV inclusions Lymphocytic infiltrate & necrosis Later fibrosis is seen

Viral myocarditis

Chagas disease

Microabscess

Cardiomyopathies

Dilated CMP

Hypertrophy, dilation, contractile dysfunction late stage of viral myocarditis Alcohol abuse Cobalt,doxorubicin Peripartum Cytoskeletal proteins mutations (dystrophin gene) Sarcomere protein genes (myosin,troponin)

Clinical features

The most common CMP (90% of cases) The most common Dx in transplant candidates At any age (peak 20-60 yrs) Sporadic or familial More in men EF <25%, progressive CHF In peripartum cases 50% recover

Morphology

Large,flabby heart >900 g Hypertrophy & dilation

in all chambers Fibrosis scant inflammation Fragile mural thrombi Emboli

Hypertrophic CMP

IHSS (LVOT obstruction) Abnormal diastolic filling Systolic anterior motion of mitral leaflet β myosin heavy chain gene mutation Dyspnea, ischemia,angina,sudden death Risk of IE Later fibrosis & CHF

Morphology

Hypertrophy of LV septum

>800 g Haphazard

hypertrophy & branching myocytes

Restrictive CMP Endomyocardial fibrosis:

idiopathic,tropical Eosinophilic endomyocardial fibrosis: (loffler syndrome) Endocardial fibroelastosis: <2 y/o children,valvular abnormality Cardiac amyloidosis Hemochromatosis Radiation injury to heart

Clinical features

Impaired diastolic filling due to inelastic ventricle

Fatigue,dyspnea,chest pain,CHF Mural thrombi in loffler syndrome Conduction system involvement by fibrosis DDx;constrictive pericarditis

Morphology

Thick & opaque fibrotic endocardium Eosinophilic infiltration(loffler syndrome) Endocardial fibroelastosis:

porcelain-like appearance,may be local Amyloidosis:green birefringence,congo red Hemochromatosis:iron stained blue,perl stain

Congenital heart disease

L-R shunts : 1-ASD 2-VSD 3-PDA R-L shunts : 1-Tetralogy of Fallot 2-TGA Coarctation of aorta

Etiology

8/1000 live births Genetic factors(trisomies) Environmental factors(rubella) Idiopathic (multifactorial):90% L-R shunt,no cyanosis until reversal of

flow due to PH R-L shunt,cyanosis from birth

Atrial septal defect (ASD)

Foramen ovale closes at birth Ostium secundum ASD:75% Ostium primum ASD :15% Sinus venosus ASD:10% The most common congenital cardiac

disease first diagnosed in adults

ASD

Ventricular septal defect (VSD)

The most common congenital heart defect at birth

Many close spontaneously in childhood

Risk of IE

VSD

Patent ductus arteriosus(PDA)

Functional closure: 1-2 days after birth Ligamentum

arteriosum: after a few months In RDS :delayed

closure Machinary murmur Risk of IE

Tetralogy of Fallot

The most common cyanotic congenital heart disease

VSD Dextraposed

overriding aorta RVH RVOT obstruction

Morphology

Boot-shaped heart Shunt extent determined by RVOT obstruction Cyanosis PH does not develop Erythrocytosis, clubbing digits IE risk Emboli:brain abscess

Transposition of great arteries

Complete form incompatible with life

Those who survive have ASD,VSD or PDA

RVH cyanosis

Coarctation of aorta

Isolated lesion in 50% Also common in turner syndrome Preductal (infantile type):

CHF, lower limbs cyanosis

weak femoral pulses Postductal (more common):

Hypertension of upper limbs

Weak pulses in legs

Coarctation of aorta

Pericardial disease

Pericarditis Pericardial effusions

Pericarditis

Primary, uncommon: Viral (most cases) Bacteria, fungi, mycobacteria Secondary, more often: Following MI or cardiac surgery Radiation Uremia (the most common systemic disorder) RF & SLE Metastases (bloody)

Course

Immediate hemodynamic complications (significant effusion)

Resolution without sequelae Progression to chronic fibrosing process

Clinical features

Atypical chest pain & friction rub Tamponade in acute forms:

distant heart sounds, distended neck veins reduced cardiac output, shock

Chronic constrictive form:

Fibrotic scar tissue

venous distention & low output

DDx: restrictive CMP

Morphology

Fibrinous exudation Shaggy Bread & butter

Pericardial effusions Serous: CHF, Albumin Serosanguineous: blunt chest trauma, malignancy Chylous: lymphatic obstruction Hemopericardium (pure blood): Aortic or myocardial rupture, penetrating trauma

Cardiac tumors

Metastases: More common than primary tumors Most often involve pericardium Lung, breast, melanoma & hematopoietic

are frequent primaries

Primary tumors (rare): Myxoma Lipoma Papillary elastofibroma Rhabdomyoma Angiosarcoma Rhabdomyosarcoma

Myxoma Most in LA Any age Sessile or pedunculated Stellate cells Mucopolysaccharide-rich stroma Smooth muscle cells Emboli Ball-valve obstruction Syncope & death

Myxoma

Rhabdomyoma

Most common primary cardiac tumors in childhood

Seen with tuberous sclerosis

Mass projecting into lumen

Solitary or multifocal

Rhabdomyoma

Spider cells contain glycogen

Wake up! we have a quiz now

1

A 20 y/o girl with atypical chest pain & fatigue has mitral regurgitation on echocardiography. which statement is false:

1-fish mouth deformity of mitral valve 2-loose edematous valve tissue 3-association with marfan syndrome 4- risk of endocarditis or death

2

A 50 y/o man with advanced gastric cancer has small vegetations on mitral valve.After an embolic episode,leading to brain lesions he died.This lesion is called :

1-libman-sacks endocarditis 2-nonbacterial thrombotic endocarditis 3-subacute infective endocarditis 4- rheumatic endocarditis

3

A young boy fell unconscious & died immediately,while playing basketball.Autopsy showed a large heart with disarray of myocytes.what is your diagnosis?

1-myocarditis 2-hypertrophic cardiomyopathy 3-restrictive cardiomyopathy 4-dilated cardiomyopathy

4

Alcohol is likely to cause…….. 1-dilated CMP 2-ischemic CMP 3-hypertrophic CMP 4-restrictive CMP

5

Amyloidosis & hemochromatosis are examples of……………..

1-dilated CMP 2-ischemic CMP 3-restrictive CMP 4-hypertrophic CMP

6

Loffler syndrome is associated with all of the following ,except….

1-thrombi & emboli 2-hypereosinophilia 3-constrictive pericarditis 4-restrictive cardiomyopathy

7

Which lesion is associated with early cyanosis?

1-ASD 2-VSD 3-PDA 4-tetralogy of fallot

8

What is the most common primary cardiac tumor in adults?

1-lipoma 2-rhabdomyoma 3-angiosarcoma 4-myxoma

9

Stellate cells in a loose stroma with smooth muscle cells are seen in……

1-rhabdomyoma 2-lipoma 3-myxoma 4-angiosarcoma

10

Vegetations of subacute infective endocarditis are distinguished from those of the acute form by……..

1-presence of fibrin & blood cells 2-size of the vegetations 3-location of vegetations 4-granulation tissue formation

11

All lesions cause hemopericardium, except?

1-uremia 2-ruptured aortic aneurysm 3-penetrating trauma to heart 4-ruptured MI

12

What is this type of endocarditis called?

13

What is this lesion called?

14

What do you see in the photographs?

15

A 22 y/o IV drug abuser is likely to present with which of the following?

1- Eosinophilic infiltration of myocardium 2-Tricuspid valve endocarditis 3-constrictive pericarditis 4- Hypertrophic cardiomyopathy

16

A 50 y/o man with a history of malignant melanoma presents with dyspnea & muffled heart sounds.what is your diagnosis?

1-Nonbacterial thrombotic endocarditis 2-Restrictive cardiomyopathy 3-Bloody pericardial effusion 4-Infective endocarditis

17

A 10 y/o child has a cardiac mass ,the cells of which contain glycogen. what is your diagnosis?

1-lipoma 2-myxoma 3-rhabomyoma 4- angiosarcoma

18

A girl with turner syndrome has high blood pressure in her upper limbs & weak pulses in her legs. what is your diagnosis?

1-tetralogy of fallot 2-ASD 3-VSD 4-coarctation of aorta

19

A 55 y/o man with bicuspid aortic valve is likely to have

1-floppy valve 2-calcification 3-fish mouth deformity 4-all of the above

20

Most cases of primary pericarditis are due to….

1-Viruses

2-Bacteria

3-Fungi or mycobacteria

4-MI or cardiac surgery

Good bye & Good luck