The Heart

Normal and Abnormal Chest

X-Rays

Blood Flow Through Heart

Coronary artery morphology

Basic Principles
myocardial cells have to do only 2 things:
contract and relax; both are aerobic, O2
requiring processes
oxygen extraction in the coronary bed is
maximal in the baseline state; therefore to
increase O2 delivery, flow must increase
large visible epicardial arteries are conduit
vessels not responsible for resistance to
flow (when normal)

Basic Principles
small, distal arterioles make up the major
resistance to flow in the normal state
atherosclerosis (an abnormal state) affects
the proximal, large epicardial arteries
once arteries are stenotic (narrowed)
resistance to flow increases unless distal,
small arterioles are able to dilate to
compensate

The function of the heart is to circulate blood

throughout the body by:

Pumping blood through the lungs removes carbon

dioxide and refreshes the blood with oxygen
The oxygenated blood is pumped to the body to
provide oxygen and nutrients and to remove waste
products.
The coronary arteries are the blood vessels that supply
blood and oxygen to the heart muscle.

MVO2 (Myocardial Oxygen

Demand)
Increases directly in proportion to
heart rate
Increases with increased
contractility
Increases with increased Wall
Tension:
i.e. increases with increasing
preload
or afterload

Wall Tension
Is related to

Pressure x Radius
Wall Thickness

Defined as: Force per unit area generated in the LV

throughout the cardiac cycle
Afterload - LV systolic pressure
Preload - LV end-diastolic pressure or volume

Myocardial Ischemia:
Occurs when myocardial oxygen demand exceeds myocardial oxygen supply

Myocardial Oxygen Supply

Determined by:
Coronary Blood Flow

&

O2 Carrying Capacity

( Flow = Pressure / Resistance)

Coronary perfusion pressure

Coronary vascular resistance

Oxygen saturation of
the blood
Hemoglobin content
of the blood

Prevalence of CAD in
Modern Society
70
60
50

% Donors

70%

40

50%

30
20
10
0

25%
<25

25-40

>40 Age (years)

Clevelend Clinic Cardiac Transplant

Donor IVUS Data-Base

Blood Supply To The Heart

2 coronary arteries branch
from the main aorta just
above the aortic valve. No
larger than drinking straws,
they divide and encircle the
heart to cover its surface
with a lacy network that
reminded physicians of a
slightly crooked crown
(coronary comes from the
Latin coronarius, belonging
to a crown or wreath). They
carry out about 130 gallons
of blood through the heart
muscle daily. (Clark, 119)

Coronary Artery Disease

Coronary artery disease is one of the most common
and serious effects of aging. Fatty deposits build up
in blood vessel walls and narrow the passageway for
the movement of blood. The resulting condition,
called atherosclerosis often leads to eventual
blockage of the coronary arteries and a heart
attack.

Cardiovascular disease claimed 39.4 percent of all

deaths or 1 of every 2.5 deaths in the United States
in 2000. CVD was about 60 percent of total
mention mortality. This means that of over
2,400,000 deaths from all causes, CVD was listed
as a primary or contributing cause on about
1,415,000 death certificates. (American Heart
Disease)

Characteristics of Atherosclerotic Plaques Associated with Various Presentations of Coronary

Artery Disease.

Libby P. N Engl J Med 2013;368:2004-2013.

Inflammatory Pathways Predisposing Coronary Arteries to Rupture and Thrombosis.

Libby P. N Engl J Med 2013;368:2004-2013.

Since 1900, CVD has been the No. 1 killer in the United
States every year but 1918.
Nearly 2,600 Americans die of CVD each day, an average of
1 death every 33 seconds.
CVD claims more lives each year than the next 5 leading
causes of death combined, which are cancer, chronic lower
respiratory diseases, accidents, diabetes mellitus, influenza
and pneumonia.
Almost 150,000 Americans killed by CVD each year are
under age 65.

can, and does,

occur in almost any artery in the body.
But in the heart its effects can be crucial.
The body depends on a strong pumping
heart to circulate life-giving blood, and
this includes to the heart muscle itself. If
the coronary arteries become blocked, the
cardiac muscle begins to fail, and so the
blood circulation decreases, which
includes the circulation to the heart
muscle itself. (Thibodeau, 494)

Normal Anatomy
Intima- the endothelium and subjacent space,
many functions.
Media- contributes static holding strength,
regulation of the extent of
vasocontriction-vasodilation.
Adventitia- major contributor to static
holding strength of the arteries

We now understand that atherosclerosis is a chronic inflammation of arteries, which

develops over decades in response to the biologic effects of risk factors.
Atherogenesis begins as a qualitative change to intact endothelial cells; when
subjected to oxidative, hemodynamic, or biochemical stimuli (from smoking,
hypertension, or dyslipidemia) and inflammatory factors, they change their
permeability to promote the entry and retention of blood-borne monocytes and
cholesterol-containing LDL particles.
Inflammation and biochemical modifications ensue, causing endothelial and
smooth-muscle cells to proliferate, produce extracellular matrix molecules, and
form a fibrous cap over the developing atheromatous plaque.
Plaques lead to clinical symptoms by producing flow-limiting stenoses (causing
stable angina) or by provoking thrombi that interrupt blood flow on either a
temporary basis (causing unstable angina) or a permanent one (causing
myocardial infarction).
Physical disruption (rupture) of the plaque exposes procoagulant material within the
core of the plaque to coagulation proteins and platelets, triggering clotting.

Atherosclerosis of the Aorta

Photograph of an autopsy specimen shows severe atherosclerotic changes in the descending

aorta, with ulceration of the media (arrows) and IMH (). Scale is in centimeters.

Castaer E et al. Radiographics 2003;23:S93-S110

2003 by Radiological Society of North America

Figure 20d. Rupture of Stanford type A typical aortic dissection.

Castaer E et al. Radiographics 2003;23:S93-S110

2003 by Radiological Society of North America

Risk Factors
Uncontrollable
Sex
Hereditary
Race
Age

Controllable
High blood
pressure
High blood
cholesterol
Smoking
Physical activity
Obesity
Diabetes
Stress and anger

Risk Factors for Heart Disease

Risk Factors for Heart Disease

OBESITY

Obesity and Organ Dysfunction

Obesity Promotes
Atherosclerosis By Many
Mechanisms involving P53

Mechanisms of Obesity-Induced Hypertension

Mechanisms involved in the pathogenesis of obesity-induced hypertension. PAI-1, plasminogen

activator inhibitor-1; Tx-A2, thromboxane A2; IL-6, interleukin-6; IL-1, interleukin-1; TNF,
tumor necrosis factor-; CRP, C-reactive protein; ROS, reactive oxygen species; FFAs, freefatty acids; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, inter-cellular adhesion
molecule-1; NO, nitric oxide; ET-1, endothelin-1; RAS, renninangiotensin system; SNS,
sympathetic nervous system; AgRP, agouti-related peptide; NPY, neuropeptide Y; POMC,
proopiomelanocortin; ARC, arcuate nucleus; -MSH, -melanocyte-stimulating hormone;
MC3R, melanocortin 3 receptor; MC4R, melanocortin 4 receptor.

Smoking Promotes
Vascular Damage via
Inflammation

Heart Attack!!!

Screening and Diagnosis

su
pp
ly

sp
ec
i fi
c

show s

Coronary
Angiography
g in
Narrow in

coronaries

Stress
Test

to
he
ar t

es
s
l
pu
im

blo
od

Electrocardiogram

me
asu
res

of
es
Sit

ele ctrical

me
as
ur
es

Stress Test to Assess Myocardial Function

EKG

Blood tests: used to evaluate kidney and

thyroid function as well as to check
cholesterol levels and the presence of
anemia.
Chest X-ray: shows the size of your heart and
whether there is fluid build up around the
heart and lungs.
Echocardiogram: shows a graphic outline of
the hearts movement
Ejection fraction (EF): determines how well
your heart pumps with each beat.

Pathophysiology of Acute
Coronary Syndromes

Acute Coronary Syndrome

Ischemic Discomfort
Unstable Symptoms

No ST-segment
elevation

Unstable
angina

History
Physical Exam

ST-segment
elevation

Non-Q
AMI

Q-Wave
AMI

ECG

Acute
Reperfusion

Coronary Stenosis Severity Prior to

Myocardial Infarction

68%

14%
18%

% Stenosis
<25
<<,,,
50-7<25><70
25-40
0 <5>40
0

Falk et al, Circulation 1995; 92: 657-71

Echocardiography

64 Slice Fast CT Scan

Coronary Angiography

Progression of Coronary Artery Disease

Microvascular Dysfunction Can Also Cause

Ischemia

Coronary Artery Disease versus Microvascular

Disease

Initiation of Atherosclerosis

Progression of Atherosclerosis

Development of Atherosclerosis at Branch

Points

Fig. 1.A schematic presentation of the initial development of atherosclerosis (vasa vasorum
hypoxia hypothesis).
(A) Normal, (B) vasoconstriction and functional hypoxia and (C) plaque
formation.
(1) A vasoconstriction of the vasa vasorum (B) causes a functional hypoxia (blue spot). The
most vulnerable site is the muscle layer with a high oxygen consumption at the branching site,
where hypertension from both sides (white arrows) compresses vasa vasorum. (2) Hypoxia in
turn leads to a damage of the endothelium. Inflammatory cells including macrophages invade
the damaged area. (3) Different macromolecules (lipoproteins etc.) and microbes (viruses and
bacteria) extravasate through the damaged endothelium and the macrophages begin
phagocytosis forming foam cells (C) (white spot). (4) Plagues grow in size and finally extrude

Risk Factors, Autoantigens and

Atherosclerosis

Schematic representation of the main events assumed to lead to the autoimmune response
against autoantigens present at endothelial level. (A) First autoantigen (oxLDL): (1) LDL
trespass the endothelial barrier and are entrapped in the sub-endothelial space; (2)
endothelial dysfunction due to different risk factors favors LDL oxidation and transforms
them into autoantigens; (3) this triggers the autoimmune reaction. (B) Second autoantigen
(Heat Shock Proteins, HSP): (1) the endothelium, stressed by the risk factors also produces
HSPs; (2) HSPs stimulate the activation of the immune system sensitized by HSPs of
different (mainly infective) origin. (C) The induction of the autoimmune reaction can also be
caused by a defective moderating action.

Figure 1.
The complex crosslink between comorbidities, lifestyle factors and
proinflammatory changes, subsequently leading to atherothrombosis.
PAI: Plasminogen activator inhibitor; TIMP: Tissue inhibitor of metalloproteinase.

Vulnerable Plaque Versus Stable Plaque

Platelet Activation and Formation of a Clot

Ruptured Plaque

A) Diagram of a cross section of a typical nonocclusive atherosclerotic plaque with two shoulder regions (S), a fibrous cap
(F), and a large lipid core (L). (B) A longitudinal section of a plaque. Note that if rupture occurred at the proximal
shoulder region, the occlusion could appear to involve a small nonocclusive plaque when, in reality, the region of most
severe narrowing is distal to the rupture site. (CF) Ruptured plaques that have occurred in very large and very
obstructive atherosclerotic plaques (T=thrombus; L=lipid core) (all hematoxylineosin stains; original magnification
1.25).

Atherosclerotic Lesion in a Human Artery.

Panel A shows a cross-sectioned coronary artery from a patient who died of a massive myocardial
infarction. It contains an occlusive thrombus superimposed on a lipid-rich atherosclerotic plaque.
Panel B is a high-power micrograph of the area in Panel A indicated by the asterisk and shows
that the contents of the atheromatous plaque have seeped through the gap in the cap into the
lumen, suggesting that plaque rupture preceded thrombosis (
Panel C illustrates the consequences of the activation of immune cells in a coronary artery.

Activating Effect of LDL Infiltration on Inflammation in the Artery.

In patients with hypercholesterolemia, excess LDL infiltrates the artery
and is retained in the intima, particularly at sites of hemodynamic
strain. Oxidative and enzymatic modifications lead to the release of
inflammatory lipids that induce endothelial cells to express leukocyte
adhesion molecules. The modified LDL particles are taken up by
scavenger receptors of macrophages, which evolve into foam cells.

Role of Macrophage Inflammation of the Artery. Monocytes recruited

through the activated endothelium differentiate into macrophages.
Several endogenous and microbial molecules can ligate patternrecognition receptors (toll-like receptors) on these cells, inducing
activation and leading to the release of inflammatory cytokines,
chemokines, oxygen and nitrogen radicals, and other inflammatory
molecules and, ultimately, to inflammation and tissue damage.

Effects of T-Cell Activation on Plaque Inflammation. Antigens presented

by macrophages and dendritic cells (antigen-presenting cells) trigger
the activation of antigen-specific T cells in the artery. Most of the
activated T cells produce Th1 cytokines (e.g., interferon-), which
activate macrophages and vascular cells, leading to inflammation.
Regulatory T cells modulate the process by secreting anti-inflammatory
cytokines (such as interleukin-10 and transforming growth factor ).

Myocardium At Risk

 Many people are able to manage

coronary artery disease with
lifestyle changes and medications.
Other people with severe coronary
artery disease may need
angioplasty or surgery.

Percutaneous Coronary Intervention

The Cascade to Heart Failure and Death

Table 2. Effects of omega-3 polyunsaturated fatty acids

Lowering of triglycerides
Reduces resting heart rate
Reduces systolic and diastolic blood pressure
Antithrombotic effect
Improved flow-mediated arterial dilatation (endothelial function)
Improved cardiac filling and myocardial efficiency
Possible increased incidence of type 2 diabetes
Anti-inflammatory effect
Anti-arrhythmic effect