Cardiovascular Pathology (modification of Dr. Veinot’s presentation)

Michel Dionne MD FRCPCfor

John P. Veinot MD FRCPCProfessor of PathologyUniversity of Ottawa

Pathology and Laboratory MedicineOttawa Hospital

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Overview

Atherosclerosis Aneurysms Ischemic heart disease Cardiomyopathies Valvular heart disease Hypertension

The Growing Burden of Heart Disease and Stroke in Canada 2003

Cerebrovascular Disease (15,409)

7%

Accidents/ Poisoning/ Violence

(13,996)6%

Infectious Diseases (2,583)

1%

Diabetes (6,137)3%

Other (33,240)15%

Respiratory (22,026)10%

AMI (20,926)9.5%

Cancer (62,606)29%

Other CVD (20,914)9.5%

Other IHD (21,693)10%

Figure 4-4 Leading causes of death, number and percentage of deaths, Canada, 1999

All Cardiovascular

Disease (78,942)

36%

Source: Health Canada, using data from Mortality File, Statistics Canada

Total Number of Deaths: 219,530Cardiovascular (ICD-9 390-459); Respiratory (ICD-9 460-519); Diabetes (ICD-9 250); Cancer (ICD-9 140-239); Infectious Diseases (ICD-9 001-139); Accidents/Poisonings/Violence (ICD-9 E800-E999)

CVS Anatomy 101

Endothelium

adventitia

intima

media

muscular artery

Aorta

Media of aorta – an elastic artery

Atherosclerosis Disease of large and medium sized arteries

(elastic and muscular), particularly:– aorta, iliac, coronary, popliteal, carotid, circle of

Willis Develop intimal lesions called atheromas or

atheromatous plaques which:– protrude into the lumen resulting in stenosis

(narrowing of lumen) and possibly occlusion (lumen blocked)

– can weaken the underlying media, possibly leading to aneurysm formation

Atherosclerosis - risk factors

Hyperlipidemia– high LDL

– low HDL Hypertension Smoking Diabetes

Age Male gender Family history/

genetics

Other: physical inactivity, diet, obesity etc.

Atherosclerosis - pathogenesis Chronic endothelial injury* resulting in endothelial dysfunction

– increased permeability – increased adhesion of leukocytes (monocytes and

lymphocytes) and platelets – accumulation of lipids in intima

Migration of monocytes into intima leading to formation of foam cells (lipid-laden macrophages)

Release of cytokines and growth factors result in smooth muscle cell migration into intima, proliferation of smooth muscle cells, deposition of extracellular matrix (e.g. collagen)

* From hemodynamic forces, hyperlipidemia, HTN, smoking etc.

From: Robbins and Cotran Pathologic Basis of Disease, 8th Edition

Aorta – fatty streaks

Aorta – fibrofatty/atheromatous plaques

Aorta – complicated plaques

Aortic arch vessels –advanced plaques causing severe stenosis

Coronary artery

Atheromatous material – foam cells (lipid laden macrophages) and cholesterol clefts

From: Robbins and Cotran Pathologic Basis of Disease, 8th Edition

Atherosclerosis - complications

Calcification Plaque hemorrhage and rupture Plaque erosion/ulceration Thrombosis Embolization of atheromatous

material (atheroemboli) Aneurysm formation and rupture

Renal infarct from embolization

Atherosclerosis - major consequences

Symptomatic disease most often affects the heart, brain, kidneys and lower extremities– Heart: angina and myocardial infarction– Brain: cerebral infarction (stroke)– Aorta (particularly abdominal):

» Aneurysms» Stenosis of ostia of major branches leading to visceral

ischemia

– Lower extremities: peripheral vascular (arterial) disease – claudication, gangrene

Aneurysm - definition

a localized abnormal dilatation of a vessel

Aneurysm types

Atherosclerotic aneurysms are the most common, but there are other types!

Aneurysms - complications

Stasis of blood Thrombosis

obstruction embolism

Mass effect Rupture

Abdominal Aortic Aneurysm (AAA)

thrombus

Aneurysm rupture

thrombus tear

vessel wall

blood

lumen

AAA rupture

Hemorrhage into surrounding tissue

Dissecting “aneurysm”

Coronary artery aneurysms secondary to vasculitis (inflammation of blood vessels)

Left atrium

Right ventricle

Left ventricle

Right atrium

Pericardium

Right lung

Left lungAortaSVC

Right atrium

Left atrium

Right ventricle

Left ventricle

Interventricular septum

Coronary artery anatomy

http://www.drchander.com/diagnoseCAD.html

Coronary artery atherosclerosis affects the epicardial arteries; tends to be more

pronounced in the proximal portion of these vessels can involve 1, 2 or all 3 of the main vessels +/- their

large branches if degree of obstruction is significant, can result in

angina (pain from myocardial ischemia) an atherosclerotic plaque can become unstable (acute

plaque lesion):– intraplaque hemorrhage– plaque rupture or erosion resulting in thrombosis

acute plaque lesions can result in an “acute coronary syndrome” (unstable angina, myocardial infarct)

Myocardial infarct terminology

Recent MI - about 24 hours old

Contraction band necrosis

Recent MI - about 3 days old

Recent MI - interstitial infiltrate of neutrophils

Recent MI - 5-7 days old

Recent MI - 7-10 days old

Residual necrotic myocytes

Phagocytosis of dead cells at margin of infarct

“Sick” myocytes bordering the infarct

Remote myocardial infarcts

Transmural rupture

Infarct rupture and tamponade

Papillary muscle rupture

Left ventricle aneurysm

Ischemic heart disease - interventions

Non-surgical thrombolysis PTCA / stenting atherectomy rotablation

Surgical Coronary Artery

Bypass Grafting (CABG) – typically using saphenous vein grafts and/or internal thoracic arteries

endarterectomy

Atherectomy device

PTCA balloon

Angiogram pre/post PTCA

Aortic valve - normal

Mitral valve - normal

Aortic stenosis - causes

Aortic stenosis causing LVH

Mitral stenosis - rheumatic

Floppy mitral valve - mitral valve prolapse (MVP)

Hypertension

PRIMARY (ESSENTIAL)– Genetic and environmental factors– Defects in sodium homeostasis, vascular smooth

muscle structure, regulation of vascular tone SECONDARY

– renal disease– vascular disease– endocrinopathies – drugs– neurogenic etc…

Reno-vascular hypertension

Hypertension - complications

enhance other diseases (risk factor) small vessel changes

– scarring/sclerosis

– microaneurysms

large vessel changes– ectasia / aneurysms / aortic regurgitation

– dissection

vessel rupture cardiac hypertrophy etc…

Arteriolo-nephrosclerosis

Brain hypertensive bleed

Hypertensive brain stem bleed

LVH (look familiar?)

Cardiomyopathy - definition

Heterogenous group of diseases of the myocardium associated with mechanical or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic.

Cardiomyopathies are either confined to the heart or are part of generalized systemic disorders often leading to cardiovascular death or progressive heart failure related disability.

Circulation 2006 113:1807-1816

Cardiomyopathy types(clinical/functional/morphologic patterns)

Dilated (DCM) – 90% Hypertrophic (HCM) Restrictive

Primary cardiomyopathy (confined to the heart) - etiology

Genetic– e.g. HCM, ARVC, mitochondrial defects,

channelopathies (e.g. LQTS)

Acquired– e.g. due to myocarditis (inflammation of the

myocardium)

Mixed Idiopathic

Secondary cardiomyopathy (part of generalized systemic disorder) – examples of etiologies

Amyloidosis Hemochromatosis Sarcoidosis Medication/Toxin induced - e.g. cancer chemotherapy,

alcoholism Autoimmune diseases - e.g. SLE, rheumatoid arthritis Infections Endocrine disorders - e.g. hypothyroidism Neuromuscular diseases - e.g. muscular dystrophies Storage diseases - e.g. glycogen storage disease Nutritional deficiencies - e.g. thiamine

Primary dilated cardiomyopathy

Primary myocardial abnormality NO SIGNIFICANT:

– coronary artery disease– valve disease– systemic arterial hypertension– systemic disorder, history of toxin exposure

etc.

Non-specific myocardial degenerative changes

DCM - clinical presentation

Progressive heart failure– systolic dysfunction– 4 chamber dilatation– hypokinesis

Arrhythmias Thromboembolism Sudden death

Familial (genetic) DCM

About 30 % of DCM Often asymptomatic LV dilatation at

detection - minority progress Examples:

– muscular dystrophy– mitochondrial defects - maternal inheritance– inherited metabolic disorders

Cardiomyopathy – genetic abnormalities

Dilated - cytoskeletal elements largely affected

dystrophin - X-linked, some muscular dystrophies

lamin desmin actin etc…

mitochondrial genes

Hypertrophic - contractile elements affected (sarcomeric genes)

myosin troponin tropomyosin myosin binding protein C etc…

Viral myocarditis and DCM

Enteroviral protease cleaves dystrophin Disrupted dystrophin / sarcoglycan

complex Similar to primary genetic defects found in

DCM

Hypertrophic cardiomyopathy

a genetic disease; autosomal dominant, variable penetrance

phenotype variations even with same mutation - ? environmental influences

myocardial hypertrophy (thickened myocardium)

diastolic dysfunction sub-aortic obstruction sudden death (60% of deaths are sudden)

Hypertrophic cardiomyopathy

Disproportionate thickening of the interventricular septum

Myocyte disarray and hypertrophy and interstitial fibrosis

HCM - diastolic dysfunction

ventricular hypertrophy myocyte disarray interstitial fibrosis myocardial microinfarcts

Cardiomyopathy - summary

Gross and histopathologic findings are non- specific but may be diagnostic

Most require clinicopathological correlation Many mimics and secondary diseases Molecular diagnosis / genetics developing