Download Path Ch 12 (p545-559) Ischemic Heart Disease Leading cause of

Path Ch 12 (p545-559)
Ischemic Heart Disease
 Leading cause of death worldwide for both men and women
 IHD – generic designation for group of pathophysiologically related syndromes resulting from myocardial
ischemia (imbalance between perfusion and demand of heart for oxygenated blood)
 Reduces availability of nutrients and removal of metabolites
 Ischemia generally less well tolerated by heart than pure hypoxia (seen in severe anemia, cyanotic heart disease,
or advanced lung disease)
 In more than 90% of cases, cause of myocardial ischemia is reduced blood flow due to obstructive
atherosclerotic lesions in coronary arteries
 IHD often called coronary artery disease (CAD) or coronary heart disease
 In most cases, there is long period of silent, slow progression of coronary lesions before symptoms appear;
syndromes of IHD are only late manifestations of coronary atherosclerosis that may have started during
childhood or adolescence
 IHD usually presents as one or more of the following
o MI – most important form of IHD, in which ischemia causes death of heart muscle
o Angina pectoris – ischemia of insufficient severity to cause infarction, but may be harbinger of MI
o Chronic IHD with heart failure
o Sudden cardiac death
 Myocardial ischemia may also be caused by coronary emboli, blockage of small myocardial blood vessels, and
lowered systemic blood pressure (e.g., shock)
 Coronary arterial obstruction ischemia can be aggravated by increase in cardiac energy demand (e.g., as occurs
with myocardial hypertrophy or tachycardia), diminished availability of blood or oxygen due to shock, or
hypoxemia; tachycardia increases oxygen demand (more contractions per unit time) as well as decreases supply
(by decreasing relative time spent in diastole when cardiac perfusion occurs)
 Overall death rate from IHD has fallen by 50% since 1963; results primarily from prevention (achieved by
modification of important risk factors, such as smoking, elevated blood cholesterol, and hypertension) and
diagnostic and therapeutic advances (allowing earlier, more effective, and safer treatments)
o Treatments include medications, coronary care units, thrombolysis for MI, percutaneous transluminal
coronary angioplasty, endovascular stents, coronary artery bypass graft (CABG) surgery, and improved
control of heart failure and arrhythmias
o Additional risk reduction can be achieved by normal blood glucose levels in diabetic patients, control of
obesity, and prophylactic anticoagulation of middle-aged men with aspirin
 Genetic determinants of coronary atherosclerosis and IHD not identical, since MI occurs in only small fraction of
individuals with coronary disease; risk of MI but not coronary atherosclerosis associated with genetic variants
that modify leukotriene B4 metabolism
 Dominant cause of IHD syndromes is insufficient coronary perfusion relative to myocardial demand, due to
chronic, progressive, atherosclerotic narrowing of epicardial coronary arteries, and variable degrees of
superimposed acute plaque change, thrombosis, and vasospasms
 More than 90% of patients with IHD have atherosclerosis of one or more epicardial coronary arteries
o Fixed lesion obstructing 75% or greater of lumen required to cause symptomatic ischemia precipitated
by exercise (most often manifested by angina); compensatory coronary arterial vasodilation no longer
sufficient to meet even moderate increases in myocardial demand
o Obstruction of 90% of lumen can lead to inadequate coronary blood flow even at rest
 LAD, left circumflex (LCX), and right coronary artery (RCA) often involved by atherosclerosis; first several
centimeters of LAD and LCX predominate (can be anywhere on RCA)
o Sometimes major secondary epicardial branches involved (diagonal branches, obtuse marginal branches,
or PDA), but atherosclerosis of intramural (penetrating) branches is rare
 Acute coronary syndromes typically initiated by unpredictable and abrupt conversion of stable atherosclerotic
plaque to unstable and potentially life-threatening atherothrombotic lesion through rupture, superficial erosion,
ulceration, fissuring, or deep hemorrhage
o In most instances, plaque change causes formation of superimposed thrombus that occludes artery
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Acute events often associated with intralesional inflammation, which mediates initiation, progression,
and acute complications of atherosclerosis
 Stable angina – results from increases in myocardial oxygen demand that outstrip ability of stenosed coronary
arteries to increase oxygen delivery; usually not associated with plaque disruption
 Unstable angina – caused by plaque rupture complicated by partially occlusive thrombosis and vasoconstriction,
which lead to severe but transient reductions in coronary blood flow
o In some cases, microinfarcts can occur distal to disrupted plaques due to thromboemboli
 In MI, acute plaque change induces total thrombotic occlusion and subsequent death of heart muscle
 Sudden cardiac death frequently involves atherosclerotic lesion in which disrupted plaque causes regional
myocardial ischemia that induces fatal ventricular arrhythmia
Angina Pectoris
 Characterized by paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort
(described as constricting, squeezing, choking, or knife-like) caused by transient (15 sec-15 min) myocardial
ischemia that falls short of inducing myocyte necrosis
 Overlapping patterns of angina include stable (typical) angina, Prinzmetal variant angina, and unstable
(crescendo) angina; caused by varying combinations of increased myocardial demand, decreased myocardial
perfusion, and coronary arterial pathology
o Not all ischemic events perceived by patients (silent ischemia)
 Stable angina – most common form; caused by imbalance in coronary perfusion (due to chronic stenosing
coronary atherosclerosis) relative to myocardial demand, such as that produced by physical activity, emotional
excitement, or any other cause of increased cardiac workload
o Usually relieved by rest (decreases demand) or administering nitroglycerin (strong vasodilator that
increases perfusion)
 Prinzmetal variant angina – uncommon form of episodic myocardial ischemia caused by coronary artery spasm
o Patients may have significant coronary atherosclerosis, but angina attacks are unrelated to physical
activity, heart rate, or blood pressure
o Generally responds promptly to vasodilators, such as nitro and calcium channel blockers
 Unstable angina – pattern of increasingly frequent pain, often of prolonged duration, that is precipitated by
progressively lower levels of physical activity or that occurs at rest
o In most patients, caused by disruption of atherosclerotic plaque with superimposed partial (mural)
thrombosis and possibly embolization or vasospasm (or both)
o Serves as a warning that AMI may be imminent (preinfarction angina)
Myocardial Infarction
 Death of cardiac muscle due to prolonged severe ischemia; by far most important form of IHD
 Can occur at virtually any age, but frequency rises progressively with increasing age and when predispositions to
atherosclerosis present
o 10% of MIs occur in people under age 40, 45% occur in people under age 65
o Men at significantly greater risk than women
o Decrease of estrogen following menopause associated with rapid development of CAD, and IHD is most
common cause of death in elderly women; postmenopausal hormonal replacement therapy doesn’t
protect against atherosclerosis and IHD
 In typical case of MI, sequence of events most likely to be followed is
o Initial event – sudden change in atheromatous plaque, which may consist of intraplaque hemorrhage,
erosion or ulceration, or rupture or fissuring
o When exposed to subendothelial collagen and necrotic plaque contents, platelets adhere, become
activated, release granule contents, and aggregate to form microthrombi
o Vasospasms stimulated by mediators released from platelets
o Tissue factor activates coagulation pathway, adding to bulk of thrombus
o Within minutes, thrombus evolves to completely occlude lumen of vessel
 Coronary angiography performed within 4 hours of onset of MI shows thrombosed coronary artery in almost
90% of cases; when angiography delayed until 12-24 hours after onset, occlusion seen only about 60% of the
time, suggesting some occlusions resolve due to fibrinolysis, relaxation of spasm, or both
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In 10% of cases, transmural MI occurs in absence of typical coronary vascular pathology; mechanisms
responsible for reduced coronary blood flow include
o Vasospasm with or without coronary atherosclerosis, perhaps in association with platelet aggregation or
due to cocaine abuse
o Emboli from left atrium in association with A fib, left-sided mural thrombus, vegetations of infective
endocarditis, intracardiac prosthetic material
o Paradoxical emboli from right side of heart or peripheral veins, which travel through patent foramen
ovale to coronary arteries
o Ischemia without detectable coronary atherosclerosis and thrombosis caused by disorders of small
intramural coronary vessels, such as vasculitis, hematologic abnormalities such as sickle cell disease,
amyloid deposition in vascular walls, and vascular dissection; lowered systemic blood pressure (shock);
or inadequate myocardial protection during cardiac surgery
Coronary arterial obstruction compromises blood supply to region of myocardium, causing ischemia, myocardial
dysfunction, and potentially myocyte deaths
o Area at risk – anatomic region supplied by obstructed artery
o Outcome depends predominantly on severity and duration of flow deprivation
Early biochemical consequence of myocardial ischemia is cessation of aerobic metabolism within seconds,
leading to inadequate production of high-energy phosphates (e.g., creatine phosphate, ATP) and accumulation
of potentially noxious metabolites (such as lactic acid)
o Severe ischemia induces loss of contractility within 60 seconds; can precipitate acute heart failure long
before myocardial cell death
o Ultrastructural changes such as myofibrillar relxation, glycogen depletion, cell and mitochondrial
swelling) develop within few minutes of onset of ischemia
o Early changes potentially reversible; severe ischemia lasting 20-30 minutes or longer leads to
irreversible damage (necrosis) of cardiac myocytes
o Ultrastructural evidence of irreversible myocyte injury (primary structural defects in sarcolemmal
membrane) develops only after prolonged, severe myocardial ischemia (when blood flow is 10% or less
of normal)
o Key feature that marks early phases of myocyte necrosis is disruption of integrity of sarcolemmal
membrane, which allows intracellular macromolecules to leak out of cells into cardiac interstitium and
ultimately into microvasculature and lymphatics in region of infarct
o Tests that measure levels of myocardial proteins in blood important in diagnosis and management of MI
o With prolonged severe ischemia, injury to microvasculature follows
In most cases of AMI, permanent damage to heart occurs when perfusion of myocardium is severely reduced for
extended interval (2-4 hours); delay in onset of permanent myocardial injury provides rationale for rapid
diagnosis in AMI: to permit early coronary intervention to establish reperfusion and salvage as much at risk
myocardium as possible
Ischemia most pronounced in subendocardium; irreversible injury of ischemic myocytes occurs first in
subendocardial zone; with more extended ischemia, wavefront of cell death moves through myocardium to
involve progressively more of transmural thickness and breadth of ischemic zone
Precise location, size, and specific morphologic features of AMI depend on
o Location, severity, and rate of development of coronary obstructions due to atherosclerosis and
thrombosis
o Size of vascular bed perfused by obstructed vessels
o Duration of occlusion
o Metabolic/oxygen needs of myocardium at risk
o Extent of collateral blood vessels
o Presence, site, and severity of coronary arterial spasm
o Other factors such as heart rate, cardiac rhythm, and blood oxygenation
Necrosis usually complete within 6 hours of onset of severe myocardial ischemia; in instances where coronary
arterial collateral system, stimulated by chronic ischemia, better developed and thereby more effective,
progression of necrosis may be 12 hours or longer
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Typically, LAD supplies most of apex of heart (distal end of ventricles), anterior wall of left ventricle, and anterior
2/3 of ventricular septum
In right dominant circulation (80%), LCX generally perfuses only lateral wall of left ventricle, and RCA supplies
entire right ventricular free wall, posterobasal wall of left ventricle, and posterior 1/3 of ventricular septum
Little blood courses through collateral circulation in normal heart; when one artery severely narrowed, blood
flows via collaterals from high-to-low-pressure system and causes channels to enlarge
Distribution of myocardial necrosis correlates with location and cause of decreased perfusion
o Most myocardial infarcts are transmural (ischemic necrosis involves full or nearly full thickness of
ventricular wall in distribution of single coronary artery); usually associated with combination of chronic
coronary atherosclerosis, acute plaque change, and superimposed thrombosis
o Subendocardial (nontransmural) infarct – constitutes area of ischemic necrosis limited to inner 1/3-1/2
of ventricular wall
 As subendocardial zone is normall least perfused region of myocardium, this area most
vulnerable to any reduction in coronary flow
 Subendocardial infarct can occur as result of plaque disruption followed by coronary thrombus
that becomes lysed before myocardial necrosis extends across full thickness of wall; in this case,
infarct will be limited to distribution of coronary artery that suffered plaque change
 Subendocardial infarcts can result from prolonged, severe reduction in systemic blood pressure,
as in shock superimposed on chronic, otherwise noncritical, coronary stenoses; in this case,
myocardial damage usually circumferential rather than limited to distribution of single major
coronary artery
o Transmural infarcts called ST elevation infarcts; subendocardial infarcts called non-ST elevation infarcts
Nearly all transmural infarcts involve at least portion of left ventricle (comprising free wall and ventricular
septum) and encompass nearly entire perfusion zone of occluded coronary artery save for narrow rim of
preserved subendocardial myocardium sustained by diffusion of oxygen and nutrients from ventricular lumen
Of MIs caused by right coronary obstruction, 15-30% extend from posterior free wall of septal portion of left
ventricle into adjacent right ventricular wall
o Isolated infarction of right ventricle is unusual (1-3% of cases), as is infarction of atria
Frequency of involvement of each of three main arterial trunks and corresponding sites of myocardial lesions
resulting in infarction are
o LAD – 40-50%; infarcts involving anterior wall of left ventricle near apex, anterior portion of ventricular
septum, and apex circumferentially
o RCA – 30-40%; infarcts involving inferior/posterior wall of left ventricle, posterior portion of ventricular
septum, and inferior/posterior right ventricular free wall in some cases
o LCX – 15-20%; infarcts involving lateral wall of left ventricle except at apex
Gross and microscopic appearance of infarct depends on duration of survival of patient following MI; areas of
damage undergo progressive sequence of morphologic changes that consist of typical ischemic coagulative
necrosis (predominant mechanism of cell death in MI, although apoptosis may occur), followed by inflammation
and repair that closely parallels tissue responses to injury at other sites
MIs less than 12 hours old usually not apparent on gross examination
o If patient died at least 2-3 hours after infarct, it is possible to highlight area of necrosis by immersion of
tissue slices in solution of triphenyltetrazolium chloride; imparts brick-red color to intact, noninfarcted
myocardium where dehydrogenase (e.g., lactate dehydrogenase) activity is preserved
 Because dehydrogenases leak out through damaged membranes of dead cell, infarct appears as
unstained pale zone
o By 12-24 hours, infarct can be identified grossly in transverse slices as reddish-blue area of discoloration
caused by stagnated, trapped blood
o Thereafter, infarct becomes progressively more sharply defined, yellow-tan, and soft
o By 10 days-2 weeks, it is rimmed by hyperemic zone of highly vascularized granulation tissue
o Over succeeding weeks, injured region evolves to fibrous scar
Typical changes of coagulative necrosis become detectable in first 6-12 hours
o Wavy fibers may be present at periphery of infarct; probably result from forceful systolic tugs of viable
fibers on immediately adjacent, noncontractile dead fibers, which stretches and folds them
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Vacuolar degeneration (myocytolysis) – large vacuolar spaces in cells that contain water
Necrotic muscle elicits acute inflammation (most prominent between 1-3 days)
Macrophages remove necrotic myocytes (most pronounced at 3-7 days), and damaged zone
progressively replaced by ingrowth of highly vascularized granulation tissue (most prominent at 1-2
weeks); as healing progresses, this is replaced by fibrous tissue
o In most instances, scarring is well advanced by end of 6th week, but efficiency of repair depends on size
of original lesion
Since healing requires participation of inflammatory cells that migrate to region of damage through intact blood
vessels, which often survive only at infarct margins, infarct heals from its margins toward its center
o Large infarct may not heal as quickly or completely as small one
o Healing infarct may appear non-uniform, with most advanced healing at periphery
o Once lesion completely healed, it is impossible to determine its age
o Infarcts may expand beyond their original borders over period of days to weeks via process of repetitive
necrosis of adjacent regions (extension)
 Central zone in which healing more advanced than periphery of infarct
 May occur because of retrograde propagation of thrombus, proximal vasospasm, progressively
impaired cardiac contractility that renders flow through moderate stenoses insufficient,
deposition of platelet-fibrin microemboli, or arrhythmia that impairs cardiac function
Most effective way to rescue ischemic myocardium threatened by infarction is reperfusion; reperfusion may also
trigger deleterious complications, including arrhythmias, myocardial hemorrhage with contraction bands,
irreversible cell damage superimposed on original ischemic injury (reperfusion injury), microvascular injury, and
prolonged ischemic dysfunction (myocardial stunning)
o Coronary intervention (i.e., thrombolysis, angioplasty, stent placement, or CABG surgery) often used in
attempt to dissolve, mechanically alter, or bypass lesion that initiated AMI; purpose of treatment is to
restore blood flow to area at risk for infarction and rescue ischemic (but not yet necrotic) heart muscle
o Early reperfusion can salvage myocardium and limit infarct size, with consequent improvement in both
short-term and long-term function and survival
o Potential benefit of reperfusion related to rapidity with which coronary obstruction alleviated (first 3-4
hours following onset are critical) and extent of correction of vascular occlusion and underlying causal
lesion (for example, thrombolysis can remove thrombus occluding coronary artery, but doesn’t alter
underlying atherosclerotic plaque that initiated it)
o Percutaneous transluminal coronary angioplasty (PTCA) with stent placement eliminates thrombotic
occlusion and also can relieve some of original obstruction and instability caused by underlying
disrupted plaque; provides flow around blocked vessel
Reperfused infarct usually hemorrhagic because vasculature injured during period of ischemia and leaks when
flow restored
o Myocytes irreversibly injured at time of reperfusion often contain contraction bands (intensely
eosinophilic intracellular stripes composed of closely packed sarcomeres) that result from exaggerated
contraction of myofibrils when perfusion reestablished, at which time, interior of dead cells with
damaged PMs exposed to high concentration of Ca2+ from plasma
Reperfusion injury may be mediated by oxidative stress, calcium overload, and potentially inflammation initiated
during reperfusion; reperfusion-induced microvascular injury causes hemorrhage and endothelial swelling that
occludes capillaries and may limit reperfusion of critically injured myocardium (no-reflow)
Biochemical abnormalities may persist for period of days to several weeks in myocytes rescued from ischemia by
reperfusion
o Stunned myocardium – state of reversible cardiac failure that usually recovers after several days
o Reperfusion frequently induces arrhythmias
o Myocardium subjected to chronic, sublethal ischemia may enter state of lowered metabolism and
function (hibernation); function of hibernating myocardium may be restored by revascularization
o Repetitive, short-lived, transient, severe ischemia may protect myocardium against infarction
(preconditioning)
Patients with MI often present with rapid, weak pulse and profuse sweating (diaphoresis); dyspnea due to
impaired contractility of ischemic myocardium and resultant pulmonary congestion and edema common
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In 10-15% of patients, onset is entirely asymptomatic and disease discovered only by EKG changes or lab
tests that show evidence of myocardial damage (silent MI); common in elderly patients and with DM
Laboratory evaluation of MI based on measuring blood levels of myoglobin, cardiac troponins T and I, MB
fraction of creatine kinase, lactate dehydrogenase, and others
o Rate of appearance of markers in peripheral circulation depends on intracellular location and molecular
weight, blood flow and lymphatic drainage in area of infarct, and rate of elimination of marker from
blood
o Most sensitive and specific biomarkers of myocardial damage are troponins I and T (proteins that
regulate calcium-mediated contraction of cardiac and skeletal muscle)
 Levels begin to rise at 2-4 hours and peak at 48 hours
 Levels stay elevated for 7-10 days after AMI
o CK-MB – formerly “gold standard”; sensitive but not specific since it is also elevated when skeletal
muscle injured; begins to rise within 2-4 hours of MI, peaks at 24 hours, and returns to normal in 72 hrs
o Troponin and CK-MB levels peak earlier in patients whose hearts successfully reperfused because
proteins are washed out of necrotic tissue more rapidly
o Unchanged levels of CK-MB and troponin over period of 2 days essentially excludes diagnosis of MI
Half of deaths associated with AMI occur within 1 hour of onset; most of these never reach hospital
Therapies given routinely during AMI include aspirin and heparin (to prevent further thrombosis), oxygen (to
minimize ischemia), nitrates (to induce vasodilation and reverse vasospasm), beta-adrenergic inhibitors (to
diminish cardiac oxygen demand and decrease risk of arrhythmias), ACE inhibitors (to limit ventricular dilation),
and maneuvers that aim to open up blocked vessels, including administration of fibrinolytic agents, coronary
angioplasty with or without stenting, and emergent CABG surgery
o Choice of therapy depends on clinical picture and expertise of treating institution
o Angioplasty is highly effective in skilled hands, while fibrinolytic therapy can be given with almost
equivalent efficacy by simple infusion
Factors associated with poor prognosis include advanced age, female gender, DM, and, as a result of cumulative
loss of functional myocardium, previous MI
Despite interventions, many patients have one or more complications following AMI
o Contractile dysfunction – myocardial infarcts produce abnormalities in left ventricular function roughly
proportional to their size; usually some degree of left ventricular failure with hypotension, pulmonary
vascular congestion, and interstitial pulmonary transudates, which may progress to frank pulmonary
edema and respiratory impairment
 Severe cardiogenic shock (pump failure) occurs in 10-15% of patients following AMI, generally
those with large infarct (>40% of left ventricle)
 Cardiogenic shock has nearly 70% mortality rate and accounts for 2/3 of in-hospital deaths
o Arrhythmias – many patients have myocardial irritability and/or conduction disturbances following MI
that lead to potentially fatal arrhythmias
 MI-associated arrhythmias include sinus bradycardia, heart block (asystole), tachycardia, PVCs,
ventricular tachycardia, and V fib
 Because of location of portions of AV conduction system in inferoseptal myocardium, infarcts of
this region may be associated with heart block
o Myocardial rupture – cardiac rupture syndromes result from softening and weakening of necrotic and
subsequently inflamed myocardium
 Cardiac rupture syndromes include
 Rupture of ventricular free wall (most common) with hemopericardium and cardiac
tamponade
 Rupture of ventricular septum (less common), leading to acute VSD and left-to-right
shunting
 Papillary muscle rupture (least common), resulting in acute onset of severe mitral
regurgitation
 Free-wall rupture is most frequent 3-7 days after MI, when coagulative necrosis, neutrophilic
infiltration, and lysis of myocardial CT have appreciably weakened infarcted myocardium
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Anterolateral wall at mid-ventricular level is most common site for post-infarction free-wall
rupture
 Risk factors for free-wall rupture include age over 60, female gender, and preexisting
hypertension
 Free-wall rupture occurs less frequently in patients without prior MI because associated fibrotic
scarring tends to inhibit myocardial tearing
 Acute free-wall ruptures usually rapidly fatal
 Fortuitously located pericardial adhesion that partially aborts rupture may result in false
aneurysm (localized hematoma communicating with ventricular cavity)
 Wall of false aneurysm consists only of epicardium and adherent parietal pericardium
and thus many still ultimately rupture
o Pericarditis – fibrinous or fibrinohemorrhagic pericarditis (Dressler syndrome) usually develops about 2nd
or 3rd day following transmural infarct as result of underlying myocardial inflammation
o Right ventricular infarction – isolated infarction of right ventricle unusual, but infarction of some right
ventricular myocardium often accompanies ischemic injury of adjacent posterior left ventricle and
ventricular septum
 Right ventricular infarcts of either type cause acute right-sided heart failure associated with
pooling of blood in venous circulation and systemic hypotension
o Infarct extension – new necrosis may occur adjacent to existing infarct
o Infarct expansion – as a result of weakening of necrotic muscle, there may be disproportionate
stretching, thinning, and dilation of infarct region (especially with anteroseptal infarcts), often
associated with mural thrombus
o Mural thrombus – with any infarct, combination of local abnormality in contractility (causing stasis) and
endocardial damage (creating thrombogenic surface) can foster mural thrombosis and potentially
thromboembolism
o Ventricular aneurysm – true aneurysms of ventricular wall bounded by myocardium that has become
scarred; aneurysms of ventricular wall are late complication of large transmural infarcts that experience
early expansion
 Thin scar tissue wall of aneurysm bulges during systole (paradoxically)
 Complications of ventricular aneurysms include mural thrombus, arrhythmias, and heart failure
 Rupture of tough fibrotic wall not a concern
o Papillary muscle dysfunction – more frequently than papillary muscle rupture, postinfarct mitral
regurgitation results from ischemic dysfunction of papillary muscle and underlying myocardium and
later from papillary muscle fibrosis and shortening, or from ventricular dilation
o Progressive late heart failure – chronic IHD
Risk of specific post-infarct complications and prognosis depend primarily on infarct size, location, and thickness
(subendocardial or transmural)
o Large transmural infracts yield higher probability of cardiogenic shock, arrhythmias, and late CHF
o Patients with anterior transmural infarcts at greatest risk for free-wall rupture, expansion, mural
thrombi, and aneurysm
o Posterior transmural infarcts more likely to be complicated by conduction blocks, right ventricular
involvement, or both
 When acute VSDs occur, they are more difficult to manage
o Patients with anterior infarcts have worse clinical course than those with inferior (posterior) infarcts
o With subendocardial infarcts, only rarely do pericarditis, rupture, and aneurysms occur
Long-term prognosis after MI depends on many factors, most important of which are quality of residual left
ventricular function and extent of vascular obstructions in vessels that perfuse viable myocardium
o Overall mortality within first year is about 30%; thereafter, there is 3-4% mortality among survivors with
each passing year
Infarct prevention through control of risk factors in individuals who have never experienced MI (primary
prevention) and prevention of reinfarction in those who have recovered from AMI (secondary prevention) are
important strategies that have received much attention and achieved considerable success
Chronic IHD
 Progressive heart failure as consequence of ischemic myocardial damage
 Ischemic cardiomyopathy – often used to describe IHD
 In most instances, there has been prior MI and sometimes previous coronary arterial interventions and/or
bypass surgery
 Usually appears post-infarction due to functional decompensation of hypertrophied non-infarcted myocardium
o Can also have severe obstructive coronary artery disease present as chronic IHD in absence of prior MI
 Hearts from patients with chronic IHD usually enlarged and heavy, due to left ventricular hypertrophy and
dilation; invariably some degree of obstructive coronary atherosclerosis
o Discrete scars representing healed infarcts usually present
o Mural endocardium may have patchy, fibrous thickenings, and mural thrombi may be present
o Microscopic findings include myocardial hypertrophy, diffuse subendocardial vacuolization, and fibrosis
 Clinically, progressive CHF may occur in patients with past episodes of MI or angina attacks
o In some individuals, progressive myocardial damage silent, and heart failure is first indication of IHD
o Diagnosis rests largely on exclusion of other cardiac diseases
o Patients with chronic IHD account for nearly half of cardiac transplant recipients
Sudden Cardiac Death
 SCD – unexpected death from cardiac causes in individuals without symptomatic heart disease or early after
symptom onset (usually within 1 hour); usually the consequence of lethal arrhythmia (e.g., asystole, V fib)
 Most frequently occurs in setting of IHD; in some cases, SCD is first clinical manifestation of IHD
 Acute myocardial ischemia – most common trigger for fatal arrhythmias
 Fatal arrhythmias usually result from acute ischemia-induced electrical instability of myocardium that is distant
from conduction system
o Arrhythmogenic foci often located adjacent to scars left by old MIs
 Non-atherosclerotic conditions associated with SCD include
o Congenital structural or coronary arterial abnormalities
o Aortic valve stenosis
o Mitral valve prolapse
o Myocarditis
o Dilated or hypertrophic cardiomyopathy
o Pulmonary hypertension
o Hereditary or acquired cardiac arrhythmias
o Cardiac hypertrophy of any cause (e.g., hypertension)
o Other miscellaneous causes, such as systemic metabolic and hemodynamic alterations, catecholamines,
and drugs of abuse, particularly cocaine and meth
 Marked coronary atherosclerosis with critical (>75%) stenosis involving one or more of major vessels present in
80-90% of SCD victims; only 10-20% of cases are of non-atherosclerotic origin
o Usually are high-grade stenosis (>90%)
o In about 50%, acute plaque disruption observed, and in about 25% diagnostic changes of AMI seen
 Many patients who die suddenly are suffering MI, but short interval from onset to death precludes development
of diagnostic myocardial changes
o Of those who were successfully resuscitated from sudden cardiac arrest, new MI occurred in only 39%
o Most SCD not associated with AMI; most of deaths result from myocardial ischemia-induced irritability
that initiates malignant ventricular arrhythmias
 Scars of previous infarcts and subendocardial myocyte vacuolization indicative of severe chronic ischemia
common in SCD patients
 Heritable conditions associated with SCD of importance because they may provide basis for intervention in
surviving family members
o Some disorders associated with recognizable anatomic abnormalities (e.g., congenital anomalies,
hypertrophic cardiomyopathy, mitral valve prolapse)
o Other heritable arrhythmias can precipitate sudden death in absence of structural cardiac pathology
(primary electrical disorders)
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Syndromes can only be diagnosed definitively by genetic testing, which is performed in those with
positive family history or unexplained nonlethal arrhythmia
Primary electrical abnormalities that predispose to SCD include long QT syndrome, Brugada syndrome, short QT
syndrome, catecholaminergic polymorphic ventricular tachycardia, Wolff-Parkinson-White syndrome, congenital
sick sinus syndrome, and isolated cardiac conduction disease
o Most important of disorders are channelopathies caused by mutations in genes required for normal ion
channel function
o Mostly autosomal-dominant inheritance; either involve genes that encode ion channels (including Na+,
K+, and Ca2+), or accessory proteins essential for normal function of same channels, which are
responsible for conducting electrical currents that mediate contraction of heart
o Long QT syndrome – characterized by prolongation of QT segment in EKGs and susceptibility to
malignant ventricular arrhythmias; gene mutations account for majority of cases of LQT syndrome
 Most frequent mutations result in decreased potassium currents
 Ion channels needed for normal function of many tissues, and certain channelopathies
associated with skeletal muscle disorders and diabetes
 Most common cardiac channelopathies are isolated disorders of heart
Prognosis of many patients vulnerable to SCD, including those with chronic IHD, markedly improved by
implantation of pacemaker or automatic cardioverter defibrillator, which senses and electrically counteracts
episodes of V fib