The Heart. Cardiac Structure and Specializations Myocardium Myocardium Valves Valves Conduction system Conduction system Blood supply Blood supply

The HeartThe Heart

Cardiac Structure and Cardiac Structure and SpecializationsSpecializations

Myocardium Myocardium ValvesValvesConduction systemConduction systemBlood supplyBlood supply

Effects of Aging on the HeartEffects of Aging on the Heart

Table 12-1Table 12-1

Heart disease: Overview of Heart disease: Overview of PathophysiologyPathophysiology

Failure of the pumpFailure of the pumpObstruction to flowObstruction to flowRegurgitant flowRegurgitant flowShunted flowShunted flowDisorders of cardiac conductionDisorders of cardiac conductionRupture of the heart or a major Rupture of the heart or a major

vesselvessel

Heart FailureHeart Failure Heart is unable to pump blood as a rate sufficient to meet the metabolic Heart is unable to pump blood as a rate sufficient to meet the metabolic

demands of the tissues or can do so only at elevated filling pressuresdemands of the tissues or can do so only at elevated filling pressures Systolic dysfunction – progressive deterioration of myocardial Systolic dysfunction – progressive deterioration of myocardial

contractile functioncontractile function Diastolic dysfunction – inability of the chamber to expand and fill during Diastolic dysfunction – inability of the chamber to expand and fill during

diastolediastole Several physiologic mechanisms maintain arterial pressure and Several physiologic mechanisms maintain arterial pressure and

perfusion of vital organsperfusion of vital organs Frank-Starling mechanismFrank-Starling mechanism Myocardial adaptations, including hypertrophy with/without chamber Myocardial adaptations, including hypertrophy with/without chamber

dilation – ventricular remodelingdilation – ventricular remodeling Activation of neurohumoral systemsActivation of neurohumoral systems

Release of norepinephrine – increases HR, contractility, vascular Release of norepinephrine – increases HR, contractility, vascular resistanceresistance

Activation of the renin-angiotensin-aldosterone systemActivation of the renin-angiotensin-aldosterone system Release of atrial natriuretic peptideRelease of atrial natriuretic peptide

Heart FailureHeart Failure

Cardiac Hypertrophy: Cardiac Hypertrophy: Pathophysiology and Progression to Pathophysiology and Progression to FailureFailure

Left-sided Heart FailureLeft-sided Heart FailureRight-sided heart failureRight-sided heart failure

Cardiac HypertrophyCardiac Hypertrophy Increased mechanical work due to pressure or volume overload or Increased mechanical work due to pressure or volume overload or

trophic signals causes myocytes to increase in sizetrophic signals causes myocytes to increase in size Increased protein synthesis, increased in DNA ploidy, increased Increased protein synthesis, increased in DNA ploidy, increased

number of mitochondria, increased size of nucleinumber of mitochondria, increased size of nuclei Pressure-overload hypertrophy – concentric increase in wall Pressure-overload hypertrophy – concentric increase in wall

thickness, sarcomere in parallelthickness, sarcomere in parallel Volume-overload hypertrophy – ventricular dilation – sarcomeres Volume-overload hypertrophy – ventricular dilation – sarcomeres

in seriesin series Oxygen supply to hypertrophied heart is tenuous, deposition of Oxygen supply to hypertrophied heart is tenuous, deposition of

fibrous tissue, shift to fetal gene expression pattern, heightened fibrous tissue, shift to fetal gene expression pattern, heightened metabolic demandmetabolic demand

Vulnerable to decompensationVulnerable to decompensation Physiologic vs pathologic hypertrophyPhysiologic vs pathologic hypertrophy CHF – variable degrees of decreased cardiac output and tissue CHF – variable degrees of decreased cardiac output and tissue

perfusion, as well as pooling of blood in the venouperfusion, as well as pooling of blood in the venous s systemsystem

Left-sided Heart FailureLeft-sided Heart Failure

CausesCausesIschemic heart diseaseIschemic heart diseaseAortic and mitral valvular diseaseAortic and mitral valvular diseaseMyocardial diseasesMyocardial diseases

Pulmonary edema – heart failure cells, Pulmonary edema – heart failure cells, Kerley B linesKerley B lines

Clinically – cough, dyspnea, orthopnea, Clinically – cough, dyspnea, orthopnea, PND, atrial fibrillation, increased vascular PND, atrial fibrillation, increased vascular and extracellular volume, pre-renal and extracellular volume, pre-renal azotemia, hypoxic encephalopathyazotemia, hypoxic encephalopathy

Rigth-sided Heart FailureRigth-sided Heart Failure

CausesCausesMost common is left-sided failureMost common is left-sided failureCor pulmonale (pulmonary hypertension)Cor pulmonale (pulmonary hypertension)

Congestion – liver and portal system, Congestion – liver and portal system, pleural, pericardial, peritoneal spaces, pleural, pericardial, peritoneal spaces, peripheral edemaperipheral edema

Clinically – Clinically – hepatosplenomegaly,peripheral edema, hepatosplenomegaly,peripheral edema, pleural effusions, ascites, hypoxia of CNSpleural effusions, ascites, hypoxia of CNS

Congenital Heart DiseaseCongenital Heart Disease

CHD = Abnormalities of the heart or CHD = Abnormalities of the heart or great vessels present from birthgreat vessels present from birth

Most – faulty embryogenesis during Most – faulty embryogenesis during the 3the 3rdrd-8-8thth week when the CVS form week when the CVS form and begin functioningand begin functioning

Worst ones don’t survive to termWorst ones don’t survive to termThose who do usually have only Those who do usually have only

discrete regions of the heart affected discrete regions of the heart affected e.g. septal defect or valvular defecte.g. septal defect or valvular defect

CHDCHD

DxDx Some when change from fetal to Some when change from fetal to

postnatal postnatal circulationcirculation 50% diagnosed by one year of life50% diagnosed by one year of life Mild forms - adulthoodMild forms - adulthood

CHDCHD IncidenceIncidence

1% of all live births1% of all live births CV defects among most common malformations and are the CV defects among most common malformations and are the

most most common cause of heart disease in childrencommon cause of heart disease in children Higher in premies and stillbornsHigher in premies and stillborns Table 12-2 Table 12-2

VSD most common VSD most common Tetralogy of Fallot most common cyanoticTetralogy of Fallot most common cyanotic

Many survive into adulthood – repairsMany survive into adulthood – repairs Common problemsCommon problems

ArrhythmiasArrhythmiasAdditional surgeryAdditional surgeryVentricular dysfunctionVentricular dysfunctionUse of prostheticsUse of prostheticsRisk of childbearingRisk of childbearing

CHDCHD ECM – swellings – endocardial cushionsECM – swellings – endocardial cushions Future valve developmentFuture valve development Day 50 – 4 chambered heartDay 50 – 4 chambered heart Signaling pathways regulating TFsSignaling pathways regulating TFs

WntWntVEgfVEgfbone morphogenetic factorbone morphogenetic factorTGF-betaTGF-betaFGFFGFNotchNotch

Heart – mechanical organ – exposed to flowing blood from Heart – mechanical organ – exposed to flowing blood from earliest stages – hemodynamic forces play a roleearliest stages – hemodynamic forces play a role

Specific micro RNAs – critical role- patterns and levels of TF Specific micro RNAs – critical role- patterns and levels of TF expressionexpression

CHDCHD

Cardiac Development – figure 12-3Cardiac Development – figure 12-3 First heart field First heart field TFs: TBX5, Hand1TFs: TBX5, Hand1 Mainly LVMainly LV Second heart field Second heart field TF: Hand2, FGF=10TF: Hand2, FGF=10 Outflow tract, RV, most of atriaOutflow tract, RV, most of atria Cardiac neural crestCardiac neural crest Septation of outflow tract, aortic Septation of outflow tract, aortic

archesarches

CHDCHD

AD mutations – partial loss of function in AD mutations – partial loss of function in one or more required factors, TFs one or more required factors, TFs usuallyusually

““The main known cause of CHD consist The main known cause of CHD consist of sporadic genetic abnormalities.”of sporadic genetic abnormalities.”

single gene mutationssingle gene mutations small chromosome deletionssmall chromosome deletions additions or deletions of whole additions or deletions of whole

chromosomeschromosomesTable 12-3Table 12-3

CHDCHD

Heterozygotes = 50% reduction in Heterozygotes = 50% reduction in activity = deranged cardiac activity = deranged cardiac developmentdevelopment

Factors work together- large protein Factors work together- large protein complexes – different single gene complexes – different single gene mutations produce similar defectsmutations produce similar defects

Signaling pathways or structural rolesSignaling pathways or structural rolesNOTCH1 – bicuspid AVNOTCH1 – bicuspid AVNOTCH2, JAGGED1 – TOFNOTCH2, JAGGED1 – TOFFibrillin – Marfan’sFibrillin – Marfan’s

CHDCHD

DiGeorge SyndromeDiGeorge SyndromeSmall deletion of 22q11.2 in 50%Small deletion of 22q11.2 in 50%44thth branchial arch and 3 branchial arch and 3rdrd and 4 and 4thth pharyngeal pharyngeal

pouches pouches Thymus, parathyroids, heartThymus, parathyroids, heartTBX1TBX1

Chromosomal aneuploidiesChromosomal aneuploidiesTurner SyndromeTurner SyndromeTrisomies 13,18, 21Trisomies 13,18, 21

21- most common genetic cause of CHD21- most common genetic cause of CHDendocardial cushion defectsendocardial cushion defects

CHDCHD

First-degree relatives of affected patients are at First-degree relatives of affected patients are at increased of CHD – subtle forms of genetic increased of CHD – subtle forms of genetic variationvariation

Environmental factors?Environmental factors?+/- genetic factors+/- genetic factorscongenital rubella infectioncongenital rubella infectiongestational diabetesgestational diabetesexposure to teratogensexposure to teratogensnutritional factors? nutritional factors? transient environmental stresses during 1transient environmental stresses during 1stst

trimester?trimester?

CHDCHD

Clinical featuresClinical features Left-to-right shuntsLeft-to-right shunts Right-to-left shuntsRight-to-left shunts Obstructive lesionsObstructive lesionsShunt= abnormal communication Shunt= abnormal communication

between chambers or vesselsbetween chambers or vesselsObstruction = narrowing (if Obstruction = narrowing (if

complete- atresia)complete- atresia)

CHDCHD

R to LR to L

HypoxemiaHypoxemia

CyanosisCyanosis

Emboli bypass lungs – brain infarction,Emboli bypass lungs – brain infarction,abscess ( paradoxical embolism)abscess ( paradoxical embolism)

Clubbing (hypertrophic Clubbing (hypertrophic osteoarthropathy)osteoarthropathy)

PolycythemiaPolycythemia

CHDCHD L to RL to R Normally low-pressure, low-resistance pulmonary circulation now Normally low-pressure, low-resistance pulmonary circulation now

sees high flow sees high flow volumes and pressuresvolumes and pressures RVHRVH Atherosclerosis of pulmonary vesselsAtherosclerosis of pulmonary vessels medial hypertrophymedial hypertrophy vasoconstrictionvasoconstriction irreversible obstructive intimal lesionsirreversible obstructive intimal lesions Pulm pressures reach systemic levelsPulm pressures reach systemic levels R to L shuntR to L shunt Eisenmenger SyndromeEisenmenger Syndrome Altered hemodynamics of CHDAltered hemodynamics of CHD Dilation, hypetrophy or bothDilation, hypetrophy or both Decreased volume and muscle mass – hypoplasia – before birth, Decreased volume and muscle mass – hypoplasia – before birth,

atrophy – atrophy – postnatallypostnatally

CHDCHD

L to RL to R

ASDASD

VSDVSD

PDAPDA

AV septal defectsAV septal defects

CHDCHD ASDASD

abnormal, fixed opening in the atrial septumabnormal, fixed opening in the atrial septumusually asymptomatic until adulthoodusually asymptomatic until adulthood3 types3 types

Secundum (90%) – center of the septumSecundum (90%) – center of the septum

Primum (5%) –adjacent to the AV valvesPrimum (5%) –adjacent to the AV valves

Sinus venosus ( 5%) – SVC, associated with APVRSinus venosus ( 5%) – SVC, associated with APVRClinicalClinical

L to RL to RPulmonary blood flow -2-4 times normalPulmonary blood flow -2-4 times normalmurmur from increased pulmonic valve blood flowmurmur from increased pulmonic valve blood flowSurgical or catheter correction – low mortality, normal long-term Surgical or catheter correction – low mortality, normal long-term

survivalsurvival PVO –oval fossa, 80% closed permanently, 20% potential opening that can PVO –oval fossa, 80% closed permanently, 20% potential opening that can

become become clinically important r-to-lclinically important r-to-l

CHDCHD VSDVSD

Most common congenital anomalyMost common congenital anomaly20-30% isolated finding20-30% isolated findingMost are associated with other cardiac anomaliesMost are associated with other cardiac anomaliesClassified by size and locationClassified by size and location90% membranous90% membranousRest are infundibular ( below the PV) or muscularRest are infundibular ( below the PV) or muscularMuscular can be multiple ( “Swiss-cheese”)Muscular can be multiple ( “Swiss-cheese”)ClinicalClinical

Large – problems from birth, RVH, pulmonary Large – problems from birth, RVH, pulmonary hypertension, correct before hypertension, correct before

irreversible irreversible changeschangesSmaller – well-toleratedSmaller – well-tolerated

CHDCHD PDAPDA

DA stays open, allowing L to R shunt from DA stays open, allowing L to R shunt from aorta to pulmonary arteryaorta to pulmonary artery

90% isolated anomaly90% isolated anomaly““machinery-like” murmurmachinery-like” murmurclose as soon as possible to prevent close as soon as possible to prevent

irreversible PHirreversible PHSome congenital lesions are ductus Some congenital lesions are ductus

dependent dependent and there by need and there by need to keep to keep the DA open-the DA open-

e.g. aortic atresia, use prostaglandin Ee.g. aortic atresia, use prostaglandin E

CHDCHD

AV septal defectAV septal defectComplete atrioventricular canal defectComplete atrioventricular canal defectPartial – primum ASD with mitral Partial – primum ASD with mitral insufficiencyinsufficiencyComplete – large combined AV septal Complete – large combined AV septal defect and a common AV valve – all 4 defect and a common AV valve – all 4 chambers communicate, all have chambers communicate, all have hypertrophyhypertrophy1/3 have Down syndrome1/3 have Down syndromeSurgically correctibleSurgically correctible

CHDCHD

R to LR to L

Tetralogy of FallotTetralogy of Fallot

Transposition of the Great ArteriesTransposition of the Great Arteries

Truncus arteriosusTruncus arteriosus

Tricupsid AtresiaTricupsid Atresia

Total Anomalous Venous Connection Total Anomalous Venous Connection

CHDCHD Tetralogy of FallotTetralogy of Fallot

4 cardinal features4 cardinal featuresVSDVSDObstruction of the right ventricular outflow tract (subpulmonary stenosis)Obstruction of the right ventricular outflow tract (subpulmonary stenosis)An aorta that overrides the VSDAn aorta that overrides the VSDRVHRVH

Embryoloigcally – anterosuperior displacement of the infundibular septumEmbryoloigcally – anterosuperior displacement of the infundibular septum““Boot-shaped” heart – marked apical RVHBoot-shaped” heart – marked apical RVHSometimes PVS, PV atresiaSometimes PVS, PV atresia

Sometines AV insufficiency, ASD Sometines AV insufficiency, ASD 25% right aortic arch25% right aortic archClinical – Classic TOF – r-to-l shuntClinical – Classic TOF – r-to-l shunt

Pink TOF – l to r shunt because of mild subpulmonary stenosisPink TOF – l to r shunt because of mild subpulmonary stenosisAs child grows obstruction becomes worseAs child grows obstruction becomes worseStenosis protects pulmonary arteries from overload and RV failure rare Stenosis protects pulmonary arteries from overload and RV failure rare

because RV decompressed by the VSDbecause RV decompressed by the VSD

CHDCHD

TGATGA

Ventriculoarterial discordVentriculoarterial discord

Aorta from RVAorta from RV

PA from LVPA from LV

Separation of the systemic and pulmonary Separation of the systemic and pulmonary

circulations – incompatible with life circulations – incompatible with life unless a shunt exists VSD or PFO or unless a shunt exists VSD or PFO or

PDA or artificial shunt –balloon PDA or artificial shunt –balloon atrial atrial septostomyseptostomy

Surgical repairSurgical repair

CHDCHD

TATA

Failure of separation into the aorta Failure of separation into the aorta and and PAPA

Single vessel giving rise to the Single vessel giving rise to the systemic, systemic, pulmonary and pulmonary and

coronary coronary circulationcirculation Associated VSDAssociated VSD

CHDCHD

TAPCTAPC

Pulmonary veins fail to join the left Pulmonary veins fail to join the left atriumatrium

PFO or ASDPFO or ASD

Aplastic Left atriumAplastic Left atrium

LV normal sizeLV normal size

CHDCHD

Obstructive Congenital AnomaliesObstructive Congenital Anomalies

Coartation of the aortaCoartation of the aorta

PS and atresiaPS and atresia

AS and atresiaAS and atresia

CHDCHD Coarctation of the AortaCoarctation of the Aorta

Males 2x femalesMales 2x femalesAssociated with Turner syndromeAssociated with Turner syndrome2 classic types2 classic types

““Infantile” –Infantile” –hypoplasia of the arch proximal to a PDA, symptomatic in hypoplasia of the arch proximal to a PDA, symptomatic in

early childhood, cyanosis over lower half of early childhood, cyanosis over lower half of body, body, surgical correction needed earlysurgical correction needed early

““Adult” –Adult” –discrete ridgelike infolding of the aorta, just opposite a discrete ridgelike infolding of the aorta, just opposite a

closed DA (ligamentum arteriosus) distal to the closed DA (ligamentum arteriosus) distal to the arch arch vessels, hypertension in upper extremities, vessels, hypertension in upper extremities, signs of arterial signs of arterial insufficiency in lower, notching of the insufficiency in lower, notching of the ribs due to collateral ribs due to collateral circulationcirculationClinical –Clinical –

murmur with thrillmurmur with thrillLVHLVH

CHDCHD PS and atresiaPS and atresia

Obstruction of the PVObstruction of the PVIsolated or part of a more complex anomalyIsolated or part of a more complex anomalyRVHRVHPoststenotic dilation of PAPoststenotic dilation of PAComplete obstruction- need shunt to surviveComplete obstruction- need shunt to surviveMild – asymptomaticMild – asymptomaticSymptomatic – surgical correctionSymptomatic – surgical correction

CHDCHD AS and atresiaAS and atresia

Vavular-hypoplastic, dysplastic, decreased numberVavular-hypoplastic, dysplastic, decreased numberSubvalular-dense fibrous tissue below the cuspsSubvalular-dense fibrous tissue below the cuspsSupravavular- aortic dysplasia, thickened and constricted, Supravavular- aortic dysplasia, thickened and constricted,

deletion on chromosome 7, elastin gene, deletion on chromosome 7, elastin gene, Williams-Williams- Beuren syndrome,Beuren syndrome,

hypercalcemia, cognitive abnormalities, facial hypercalcemia, cognitive abnormalities, facial anomaliesanomalies

Hypoplastic left heart syndrome – severe stenosis of atresia Hypoplastic left heart syndrome – severe stenosis of atresia – – underdevelopment of LV and aorta – underdevelopment of LV and aorta – endocardial endocardial fibroelastosisfibroelastosis

Clinical – systolic murmur, thrill, LVH, antibiotic prophylaxis Clinical – systolic murmur, thrill, LVH, antibiotic prophylaxis for for SBE, avoid strenuous activity, sudden deathSBE, avoid strenuous activity, sudden death

Ischemic Heart DiseaseIschemic Heart Disease

Leading cause of death worldwide for Leading cause of death worldwide for both men and woman.both men and woman.

Ischemia = oxygen and nutrients Ischemia = oxygen and nutrients insufficiencyinsufficiency

90% cause is atherosclerotic lesions in 90% cause is atherosclerotic lesions in the coronary arteries, thus “coronary the coronary arteries, thus “coronary artery disease”artery disease”

Other causes – emboli, blockage of Other causes – emboli, blockage of small myocardiql blood vessels, shocksmall myocardiql blood vessels, shock


Angina PectorisAngina PectorisMyocardial InfarctionMyocardial InfarctionChronic IHD – ischemic Chronic IHD – ischemic

cardiomyopathycardiomyopathySudden cardiac deathSudden cardiac death


Peak in mortality in 1963, fallen by 50% Peak in mortality in 1963, fallen by 50% since then due to prevention, diagnostic and since then due to prevention, diagnostic and therapeutic advancestherapeutic advances

The dominant cause of the IHD syndromes The dominant cause of the IHD syndromes is insufficient coronary perfusion relative to is insufficient coronary perfusion relative to myocardial demand, due to chronic, myocardial demand, due to chronic, progressive atherosclerotic narrowing of the progressive atherosclerotic narrowing of the epicardial coronary arteries, and variable epicardial coronary arteries, and variable degrees of superimposed acute plaque degrees of superimposed acute plaque change, thrombosis, and vasospasmchange, thrombosis, and vasospasm


Fixed lesion obstructing Fixed lesion obstructing > > 75% of the lumen 75% of the lumen leads to Symptomatic ischemia precipitated leads to Symptomatic ischemia precipitated by exerciseby exercise

Obstruction of 90% leads to symptoms even Obstruction of 90% leads to symptoms even at restat rest

May lead to formation of collateral vessels May lead to formation of collateral vessels over timeover time

Clinically significant stenotic lesions tend to Clinically significant stenotic lesions tend to predominate in the first several centimeters predominate in the first several centimeters of the LAD and LCX and along the entire of the LAD and LCX and along the entire length of the RCAlength of the RCA

Angina PectorisAngina Pectoris

Paroxysmal and usually recurrent Paroxysmal and usually recurrent attacks of substernal or precordial attacks of substernal or precordial chest discomfort cause by transient chest discomfort cause by transient myocardial ischemia that fall short of myocardial ischemia that fall short of inducing myocyte necrosisinducing myocyte necrosis

Three overlapping patternsThree overlapping patternsStable or typical anginaStable or typical anginaPrinzmetal variant anginaPrinzmetal variant anginaUnstable or crescendo anginaUnstable or crescendo angina

Myocardial InfarctionMyocardial Infarction

Death of cardiac muscle due to prolonged severe ischemiaDeath of cardiac muscle due to prolonged severe ischemia Sequence of events in typical MISequence of events in typical MI

Sudden change in an atheromatous plaqueSudden change in an atheromatous plaque Platelets adhere, become activated, release their Platelets adhere, become activated, release their

granule contents, and aggregate to form microthrombi granule contents, and aggregate to form microthrombi when exposed to subendothelial collagen and necrotic when exposed to subendothelial collagen and necrotic plaque contentsplaque contents

Vasospasm is stimulated by mediators released by Vasospasm is stimulated by mediators released by plateletsplatelets

Tissue factor activates the coagulation pathway, adding Tissue factor activates the coagulation pathway, adding to the bulk of the thrombusto the bulk of the thrombus

Frequently within minutes, the thrombus evolves to Frequently within minutes, the thrombus evolves to completely occlude the lumencompletely occlude the lumen


Myocardial responseMyocardial response Cessation of aerobic metabolism within seconds leading Cessation of aerobic metabolism within seconds leading

to inadequate high-energy phosphates and to inadequate high-energy phosphates and accumulation of lactic acidaccumulation of lactic acid

Severe ischemia induces loss of contractility within 60 Severe ischemia induces loss of contractility within 60 secondsseconds

Ultrastructural changes – potentially reversible, develop Ultrastructural changes – potentially reversible, develop within a few minuteswithin a few minutes

Myofibrillar relaxationMyofibrillar relaxationGlycogen depletionGlycogen depletionCell and mitochondrial swellingCell and mitochondrial swelling


Table 12-4 Approximate time of onset of Table 12-4 Approximate time of onset of key events in ischemic cardiac myocyteskey events in ischemic cardiac myocytes

Key feature in the early phases of Key feature in the early phases of myocyte necrosis – disruption of the myocyte necrosis – disruption of the integrity of the sarcolemmal membrane integrity of the sarcolemmal membrane allowing intracellular macromolecules to allowing intracellular macromolecules to leak out of cells into the cardiac leak out of cells into the cardiac interstitium and ultimately into the interstitium and ultimately into the microvasculature and lymphatics in the microvasculature and lymphatics in the region of the infarctregion of the infarct


In most cases of acute MI, permanent In most cases of acute MI, permanent damage to the heart occurs when the damage to the heart occurs when the perfusion of the myocardium is severely perfusion of the myocardium is severely reduced for an extended interval (usually at reduced for an extended interval (usually at least 2-4 hours). This delay in the onset of least 2-4 hours). This delay in the onset of permanent myocardial injury provides the permanent myocardial injury provides the rationale for rapid diagnosis in acute MI – to rationale for rapid diagnosis in acute MI – to permit early coronary intervention, the permit early coronary intervention, the purpose of which is to establish reperfusion purpose of which is to establish reperfusion and salvage as much “at risk” myocardium and salvage as much “at risk” myocardium as possible.as possible.


Precise location, size, and specific morphologic features of Precise location, size, and specific morphologic features of an acute MI depend on:an acute MI depend on: Location, severity, and rate of development of coronary Location, severity, and rate of development of coronary

obstructionobstruction Size of the vascular bed perfused by the obstructed Size of the vascular bed perfused by the obstructed

vesselsvessels Duration of the occlusionDuration of the occlusion Metabolic/oxygen needs of the myocardium at riskMetabolic/oxygen needs of the myocardium at risk Extent of collateral vesselsExtent of collateral vessels Presence, site, severity of coronary arterial spasmPresence, site, severity of coronary arterial spasm Other factors – HR, rhythm, blood oxygenationOther factors – HR, rhythm, blood oxygenation


TypicallyTypicallyLAD – apex, anterior wall of LV, anterior 2/3 LAD – apex, anterior wall of LV, anterior 2/3

of ventricular septumof ventricular septumThe coronary artery that perfuses the The coronary artery that perfuses the

posterior third of the septum is called posterior third of the septum is called dominant ( either the LCX or RCA)dominant ( either the LCX or RCA)

Right dominant circulation (4/5 of Right dominant circulation (4/5 of population) population) LCX – lateral wall of the LVLCX – lateral wall of the LVRCA – entire RV free wall, posterobasal wall of RCA – entire RV free wall, posterobasal wall of

the LV, posterior third of the septumthe LV, posterior third of the septum


Transmural vs subendocardial Transmural vs subendocardial infarctioninfarctionMost MIs are transmural – full thickness Most MIs are transmural – full thickness

in the distribution of a single artery, ST in the distribution of a single artery, ST elevation elevation

Subendocardial – area of necrosis Subendocardial – area of necrosis limited to inner 1/3 to1/2 of ventricular limited to inner 1/3 to1/2 of ventricular wall, non-ST elevation, normally the wall, non-ST elevation, normally the least perfused area of the myocardium, least perfused area of the myocardium, most vulnerable to ischemiamost vulnerable to ischemia


Infarct modification by reperfusionInfarct modification by reperfusionReperfusion – most effective way to “rescue” Reperfusion – most effective way to “rescue”

ischemic myocardiumischemic myocardiumMay trigger deleterious complications May trigger deleterious complications

ArrhythmiasArrhythmiasMyocardial hemorrhage with contraction bandsMyocardial hemorrhage with contraction bandsIrreversible cell damage superimposed on the Irreversible cell damage superimposed on the

original ischemic injury (reperfusion injury)original ischemic injury (reperfusion injury)Microvascular injuryMicrovascular injuryProlonged ischemic dysfunction (myocardial Prolonged ischemic dysfunction (myocardial

stunning)stunning)


Appearance of reperfused Appearance of reperfused myocardiummyocardiumHemorrahagicHemorrahagicIrreversibly injured myocytes – Irreversibly injured myocytes –

contraction bands contraction bands Reperfusion not only salvages reversible Reperfusion not only salvages reversible

injured cells but alters the morphology injured cells but alters the morphology of lethally injured cellsof lethally injured cells


Consequences and ComplicationsConsequences and Complications Contractile dysfunctionContractile dysfunction ArrhythmiasArrhythmias Myocardial ruptureMyocardial rupture PericarditisPericarditis Right ventricular infarctionRight ventricular infarction Infarct extensionInfarct extension Infarct expansionInfarct expansion Mural thrombusMural thrombus Ventricular aneurysmVentricular aneurysm Papillary muscle dysfunctionPapillary muscle dysfunction Progressive late heart failureProgressive late heart failure

Morphologic Changes in Acute Morphologic Changes in Acute Myocardial InfarctionMyocardial Infarction

Early – Risk of ArrhythmiaEarly – Risk of ArrhythmiaTime Time Gross LM Gross LM

½-4 hours½-4 hours NoneNone None, variable waviness None, variable waviness of fibers at borderof fibers at border

4-12 hours4-12 hours Occasional Occasional dark mottlingdark mottling

Early coagulation Early coagulation necrosis, edema, necrosis, edema, hemorrhagehemorrhage

12-24 hours12-24 hours Dark mottlingDark mottling Ongoing coagulation Ongoing coagulation necrosis, pyknosis of necrosis, pyknosis of nuclei, myocyte nuclei, myocyte eosinophilia,contraction eosinophilia,contraction band necrosis, early band necrosis, early neutrophilic inflitrationneutrophilic inflitration

1-3 days1-3 days Mottling with Mottling with yellow-tan yellow-tan infarct centerinfarct center

Coagulation necrosis Coagulation necrosis with loss of nuclei and with loss of nuclei and striations;striations;

Brisk interstitial Brisk interstitial neutrophil infiltration neutrophil infiltration

Middle – Risk of Myocardial Middle – Risk of Myocardial RuptureRupture

Time Gross LM Time Gross LM 3-7 days3-7 days Hyperemic Hyperemic border; border; central central yellow-tan yellow-tan softeningsoftening

Beginning disintegration Beginning disintegration ofdead myofibers, ofdead myofibers,

dyingneutrophils, early dyingneutrophils, early phagocytosis by phagocytosis by

macrophages macrophages

7-10 days7-10 days Maximally Maximally yellow-tan yellow-tan and soft, with and soft, with depressed depressed marginsmargins

Well-developed Well-developed phagocytosis of dead phagocytosis of dead cells; early formation, of cells; early formation, of granulation tissue at granulation tissue at marginsmargins

10-14 days10-14 days Red-gray Red-gray depressed depressed infarct infarct bordersborders

Well- established Well- established granulation tissuegranulation tissue

Late – Risk of Ventricular Late – Risk of Ventricular AneurysmAneurysm

TimeTime Gross Gross LMLM

2-8 weeks2-8 weeks Gray-white Gray-white scar, scar, progressive progressive from border from border toward core toward core of infarctof infarct

Increased Increased collagen with collagen with decreased decreased cellularitycellularity

>2 months>2 months Scarring Scarring completecomplete

Dense Dense collagenous collagenous scarscar

Serum Enzyme changes in Serum Enzyme changes in Acute MIAcute MI

TimeTime CK-MBCK-MB Troponin ITroponin I(most sensitive (most sensitive and specific)and specific)

LDHLDH

6 hours6 hours Weakly Weakly positivepositive

Weakly Weakly positivepositive

12-16 12-16 hourshours

Strongly Strongly positivepositive

Strongly Strongly positivepositive

24 24 hours__hours__

2 2 days____days____

3 3 days____days____

4-7 days4-7 days

Peaks____Peaks____

Persists__Persists____

Negative_Negative___

Peaks____Peaks____



PersistsPersists

Peaks____Peaks____

Persists Persists

Sudden Cardiac DeathSudden Cardiac Death

Usually the consequence of a lethal arrhythmiaUsually the consequence of a lethal arrhythmia Acute myocardial ischemia is the most common trigger for Acute myocardial ischemia is the most common trigger for

fatal arrhythmiasfatal arrhythmias Nonatherosclerotic causesNonatherosclerotic causes

Congenital structural of coronary arterial abnormalitiesCongenital structural of coronary arterial abnormalities ASAS MVPMVP MyocarditisMyocarditis Dilated or hypertrophic cardiomyopathyDilated or hypertrophic cardiomyopathy Pulmonary hypertensionPulmonary hypertension Hereditary or acquired arrhythmiasHereditary or acquired arrhythmias Cardiac hypertrophy of any cuaseCardiac hypertrophy of any cuase Other miscellaneousOther miscellaneous

Hypertensive Heart DiseaseHypertensive Heart Disease

Systemic (Left-sided) hypertensive heart Systemic (Left-sided) hypertensive heart diseasediseaseLVH (concentric usually) in absence of other LVH (concentric usually) in absence of other

CV pathologyCV pathologyHistory of pathological evidence of History of pathological evidence of

hypertensionhypertensionPulmonary (Right-sided) hypertensive Pulmonary (Right-sided) hypertensive

heart disease (Cor pulmonale)heart disease (Cor pulmonale)Table 12-6 -disorders predisposing to cor Table 12-6 -disorders predisposing to cor

pulmonalepulmonale

Valvular Heart DiseaseValvular Heart Disease

Valvular degeneration associated with calcificationValvular degeneration associated with calcification Calcific aortic stenosisCalcific aortic stenosis Calcific stenosis of congenitally bicuspid aortic valveCalcific stenosis of congenitally bicuspid aortic valve Mitral annular calcificationMitral annular calcification

Mitral Valve Prolapse (Myxomatous degeneration of the Mitral Valve Prolapse (Myxomatous degeneration of the mitral valve)mitral valve)

Rheumatic Fever and rheumatic heart diseaseRheumatic Fever and rheumatic heart disease Infective endocarditisInfective endocarditis Noninfected vegetationsNoninfected vegetations

Nonbacterial thrombotic endocarditisNonbacterial thrombotic endocarditis Endocarditis of systemic lupus erythematosus (Libman-Sacks disease)Endocarditis of systemic lupus erythematosus (Libman-Sacks disease)

Carcinoid heart diseaseCarcinoid heart disease Complications of artificial valvesComplications of artificial valves

Valvular Heart DiseaseValvular Heart Disease

Stenosis – pressure overloadStenosis – pressure overload Insufficiency (regurgitation) – volume overloadInsufficiency (regurgitation) – volume overload Acquired stenosis of the aortic and mitral valves Acquired stenosis of the aortic and mitral valves

account for 2/3 of all cases of valve diseaseaccount for 2/3 of all cases of valve disease Most frequentMost frequent

AS – calcification of normal or bicuspid valveAS – calcification of normal or bicuspid valve AI – dilation of ascending aortaAI – dilation of ascending aorta MS – RHDMS – RHD MI – MVPMI – MVP Table 12-7 Major etiologies of acquired lesionsTable 12-7 Major etiologies of acquired lesions

Mitral Valve ProlapseMitral Valve Prolapse

One or more of the leaflets are floppy and prolapse into the One or more of the leaflets are floppy and prolapse into the left atrium during systoleleft atrium during systole

Myxomatous degenerationMyxomatous degeneration Most patient are asymptomaticMost patient are asymptomatic Midsystolic clickMidsystolic click Chest pain, dypsnea, fatigueChest pain, dypsnea, fatigue ComplicationsComplications

Infective endocarditisInfective endocarditis MIMI StrokeStroke ArrhythmiasArrhythmias

Rheumatic Fever and Rheumatic Fever and Rheumatic Heart DiseaseRheumatic Heart Disease

Rheumatic feverRheumatic fever Acute, immunologically mediated, occurs a few weeks Acute, immunologically mediated, occurs a few weeks

after an episode of group A strep pharyngitisafter an episode of group A strep pharyngitis Antibodies and T cell-mediated reactions against M Antibodies and T cell-mediated reactions against M

proteins cross-react with heart self- antigensproteins cross-react with heart self- antigens Jones criteriaJones criteria

Major – migratory polyarthritis of large joints, Major – migratory polyarthritis of large joints, pancarditis, subcutaneous nodules, erythema pancarditis, subcutaneous nodules, erythema marginatum, Sydenham choreamarginatum, Sydenham chorea

Minor – fever, arthralgia, elevated acute-phase Minor – fever, arthralgia, elevated acute-phase reactantsreactants

2 major or 1 major and 2 minor + evidence of a 2 major or 1 major and 2 minor + evidence of a preceeding strep infectionpreceeding strep infection

Rheumatic Fever and Rheumatic Fever and Rheumatic Heart DiseaseRheumatic Heart Disease

RF – Aschoff bodies, caterpillar cells, RF – Aschoff bodies, caterpillar cells, Mac Callum plaquesMac Callum plaques

RHD – leaflet thickening, RHD – leaflet thickening, commissural fusion and shortening, commissural fusion and shortening, thickening and fusion of the thickening and fusion of the tendinous cordstendinous cords

Infective EndocarditisInfective Endocarditis

Colonization or invasion of the heart valves or the Colonization or invasion of the heart valves or the mural endocardium by a microbemural endocardium by a microbe

Vegetations – thrombotic debris and organisms, Vegetations – thrombotic debris and organisms, destruction of the tissuedestruction of the tissue

Acute – infection of a previously normal heart by Acute – infection of a previously normal heart by a virulent organism, S. Aureusa virulent organism, S. Aureus

Subacute – insidious infection of deformed valves Subacute – insidious infection of deformed valves with less virulent organisms, S viridnas, HACEK, S. with less virulent organisms, S viridnas, HACEK, S. epidermidisepidermidis

Table 12-8 Diagnostic criteria for IETable 12-8 Diagnostic criteria for IE

CardiomyopathiesCardiomyopathies

Dilated cardiomyopathyDilated cardiomyopathyArrhythmogenic right ventricular Arrhythmogenic right ventricular

cardiomyopathycardiomyopathyHypertrophic cardiomyopathyHypertrophic cardiomyopathyRestrictive cardiomyopathyRestrictive cardiomyopathyMyocarditisMyocarditisOther causes of myocardial diseaseOther causes of myocardial disease

CardiomyopathiesCardiomyopathies

Table 12-10 Cardiomyopathy and Table 12-10 Cardiomyopathy and Indirect Indirect Myocardial DysfunctionMyocardial Dysfunction

Table 12-11 Conditions associated Table 12-11 Conditions associated with with Heart Muscle diseaseHeart Muscle disease

Figure 12-32 Causes and Figure 12-32 Causes and consequences of consequences of Dilated and Dilated and Hypertrophic Hypertrophic CardiomyopathyCardiomyopathy

Table 12-12 Major Causes of Table 12-12 Major Causes of MyocarditisMyocarditis

Other Causes of Myocardial Other Causes of Myocardial DiseaseDisease

Cardiotoxic drugsCardiotoxic drugsCatecholaminesCatecholaminesAmyloidosisAmyloidosis Iron overloadIron overloadHyperthyroidisnHyperthyroidisnHypothyroidismHypothyroidism

Pericardial DiseasePericardial Disease

Pericardial effusion and Pericardial effusion and hemopericardiumhemopericardiumCardiac tamponadeCardiac tamponade

Pericarditis – Table 12-13 - causesPericarditis – Table 12-13 - causesAcute pericarditis – friction rub, fever, painAcute pericarditis – friction rub, fever, painChronic or healed pericarditis – adhesive, Chronic or healed pericarditis – adhesive,

constrictiveconstrictiveHeart disease associated with Heart disease associated with

rheumatologic disordersrheumatologic disorders

Tumors of the heartTumors of the heart

Primary cardiac tumorsPrimary cardiac tumorsMyxoma – most common in adults, ball-valve Myxoma – most common in adults, ball-valve

obstruction. Carney complexobstruction. Carney complexLipomaLipomaPapillary fibroelastomaPapillary fibroelastomaRhabdomyoma – most commonin children, Rhabdomyoma – most commonin children,

TSTSSarcomaSarcoma

Cardiac effects of noncardiac neoplasms Cardiac effects of noncardiac neoplasms – – Table 12-14Table 12-14

Cardiac TransplantationCardiac Transplantation

Rejection – resembles myocarditisRejection – resembles myocarditisGraft arteriopathy – silent MisGraft arteriopathy – silent Mis1-year survival - 70-80%, 5-year - 1-year survival - 70-80%, 5-year -

>60%>60%

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The Heart. Cardiac Structure and Specializations Myocardium Myocardium Valves Valves Conduction system Conduction system Blood supply Blood supply