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
Oxygen saturation of the blood
Hemoglobin content of the blood
( Flow = Pressure / Resistance)
Coronary perfusion pressure
Coronary vascular resistance
0 10 20 30 40 50 60 70
25%
50%
70%
% Donors
Clevelend Clinic Cardiac Transplant Donor IVUS Data-Base
Prevalence of CAD in Modern Society
<25 25-40 >40 Age (years)
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)
Blood Supply To The Heart
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 it’s 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.∗
Castañer 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.
Castañer E et al. Radiographics 2003;23:S93-S110
©2003 by Radiological Society of North America
Risk Factors
Uncontrollable Uncontrollable
•Sex
•Hereditary
•Race
•Age
Controllable 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 involved in the pathogenesis of obesity-induced hypertension. PAI-1, plasminogen activator inhibitor-1; Tx-A2, thromboxane A2; IL-6, interleukin-6; IL-1β, interleukin-1β; TNFα, tumor necrosis factor-α; CRP, C-reactive protein; ROS, reactive oxygen species; FFAs, free- fatty acids; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, inter-cellular adhesion molecule-1; NO, nitric oxide; ET-1, endothelin-1; RAS, rennin–angiotensin system; SNS, sympathetic nervous system; AgRP, agouti-related peptide; NPY, neuropeptide Y; POMC, proopiomelanocortin; ARC, arcuate nucleus; α-MSH, α-melanocyte-stimulating hormone;
MC3R, melanocortin 3 receptor; MC4R, melanocortin 4 receptor.
Mechanisms of Obesity-Induced Hypertension
Smoking Promotes Vascular Damage via Inflammation
Heart Attack!!!
Screening and Diagnosis
Stress Stress TestTest
measures measures blood
blood
supply
supply to heart to heart
Coronary Coronary Angiography Angiography
specific
specific showsshows
coronariescoronaries
Narrowing in Narrowing in Site
s of Site
s of
Electro- Electro- cardiogram cardiogram
measures measures
electrical electrical
impulses impulses
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 heart’s 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
ST-segment elevation
Unstable Non-Q Q-Wave
angina AMI AMI
ECG
Acute
Reperfusion History
Physical Exam
<<,,,
<25><70 50-7 25-40 0 <5>40
0
% Stenosis 68%
18%
14%
Coronary Stenosis Severity Prior to Myocardial Infarction
Falk et al, Circulation 1995; 92: 657-71
<25
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 into the lumen of the main artery. After neovascularization, a hemorrhagic rupture may occur leading to an obstruction. Dotted line in Fig 1A stands for media-intima border, where the outward oxygen diffusion from lumen and the inward diffusion from the vasa vasorum meet.
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. (C–F) Ruptured plaques that have occurred in very large and very obstructive atherosclerotic plaques (T=thrombus; L=lipid core) (all hematoxylin–eosin 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 pattern-recognition 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
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
Table 2. Effects of omega-3 polyunsaturated fatty acids
