Cardiovascular Pathology

(modification of Dr. Veinot’s presentation)

Michel Dionne MD FRCPC

for
John P. Veinot MD FRCPC
Professor of Pathology
University of Ottawa
Pathology and Laboratory Medicine
Ottawa Hospital
You may only access and use this PowerPoint
presentation for educational purposes. You
may not post this presentation online or
distribute it without the permission of the
author.
Overview
 Atherosclerosis
 Aneurysms
 Ischemic heart disease
 Cardiomyopathies
 Valvular heart disease
 Hypertension
 Figure 4-4 Leading causes of death, number and percentage of
deaths, Canada, 1999
Respiratory (22,026)
10% Other IHD (21,693)
10%

AMI (20,926)
9.5%
Other (33,240) All
15%
Cardiovascular
Cerebrovascular Disease
Disease (15,409) (78,942)
7%
36%
Diabetes (6,137)
3%
Infectious Diseases
(2,583) Other CVD (20,914)
1% 9.5%

Accidents/
Cancer (62,606) Poisoning/ Violence
29% (13,996)
6%
Total Number of Deaths: 219,530
Cardiovascular (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)

Source: Health Canada, using data from Mortality File, Statistics Canada
The Growing Burden of Heart Disease and Stroke in Canada 2003
CVS Anatomy 101
Endothelium
 muscular artery

intima

media

adventitia
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
Age Hyperlipidemia

Male gender – high LDL

– low HDL
Family history/
genetics Hypertension
Smoking
Diabetes

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 blood

lumen

thrombus tear

vessel
wall
 AAA rupture
Hemorrhage into
surrounding tissue
Dissecting “aneurysm”
Coronary artery aneurysms secondary to
vasculitis (inflammation of blood vessels)
 Left lung
SVC Aorta

Left atrium
Pericardium

Right lung Right

atrium

Left
ventricle
Right
ventricle
 Left atrium

Right
atrium

Left
ventricle

Right
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

“Sick” myocytes Phagocytosis of dead Residual necrotic

bordering the infarct cells at margin of infarct myocytes
Remote myocardial infarcts
Transmural
rupture
Infarct rupture and tamponade
Papillary muscle rupture
Left ventricle
aneurysm
Ischemic heart disease -
interventions
Non-surgical Surgical
 thrombolysis  Coronary Artery
 PTCA / stenting Bypass Grafting
 atherectomy
(CABG) – typically
using saphenous vein
 rotablation
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 Hypertrophic - contractile
elements largely affected elements affected
 dystrophin - X-linked, some (sarcomeric genes)
muscular dystrophies  myosin
 lamin  troponin
 desmin
 tropomyosin
 actin
 myosin binding protein C
 etc…
 etc…

 mitochondrial genes
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