Cardiology Core Curriculum - part 4 pdf

elevation myocardial infarctionOptions for reperfusion therapy include fibrinolytic therapy andprimary percutaneous coronary intervention PCI, either withpercutaneous transluminal corona

approximately 18 hours, and return to normal in approximately

3 days (Figure 6.5).6

Cardiac troponins T (cTnT) and I (cTnI) are contractile proteins thatare released in response to myocardial necrosis Like CK and CK-MB,these enzymes are detectable 3–6 hours after the onset of chest pain

Myoglobin CK/CK-MB Troponin T/I LDH

Hours from onset of infarction

15

20

Figure 6.5 Time course of serum marker release in acute myocardial infarction (See text for details.) CK, creatinine kinase; LDH, lactate dehydrogenase Adapted with permission from Antman 6

however, in that they remain elevated for up to 14 days afterinfarction This prolonged detection window facilitates the diagnosis

of remote infarction (i.e an infarct that occurred in the days or weeksbefore presentation) but makes the diagnosis of early recurrentinfarction difficult Because cTnT and cTnI are not found in adultskeletal muscle, they are highly specific for myocardial injury andthus are excellent markers for confirming the diagnosis of MI Thenormal reference range for the cardiac troponins is set at a very lowlevel; as a result, troponins are very sensitive for the detection of smallamounts of myocardial necrosis Indeed, it has recently been shownthat patients with minor myocardial necrosis, as evidenced by lowlevel troponin elevation in the absence of CK and CK-MB elevation,are at increased risk for the development of adverse clinicaloutcomes.7This finding has led to a revised, more liberal definition ofmyocardial infarction that now includes patients with low leveltroponin elevation, even if CK and CK-MB are normal

Myoglobin is a small cytosolic molecule that is rapidly released fromischemic muscle and promptly cleared by the kidney Serum levels ofmyoglobin rise earlier than other available markers, and elevated levelscan be detected as early as 2 hours after the onset of chest pain.Myoglobin peaks at approximately 6 hours and returns to normallevels within 18–24 hours (see Figure 6.5) Widespread use of serummyoglobin for the detection of MI has been limited by concerns aboutpoor cardiac specificity Skeletal muscle trauma and renal failure canraise serum myoglobin levels in a non-specific manner Nevertheless,myoglobin remains a very useful early marker because of its rapidrelease and renal clearance, and it is more sensitive than CK-MB fordetecting MI within the first few hours after presentation An elevatedmyoglobin should be confirmed with a more specific marker at a latertime point, such as CK-MB, cTnT, or cTnI.8

Radionuclide imaging

New high-resolution agents, such as 99mTc-sestamibi and 99mtetrofosmin, are now available for myocardial perfusion imaging.These radionuclides, unlike thallium-201, do not redistribute aftertheir initial deposition This property allows these agents to be given

Tc-by intravenous injection during an episode of suspected ischemicpain, with imaging performed following stabilization and/or therapy.The images obtained provide a “snapshot” of myocardial perfusion atthe time the tracer was injected This strategy may be a particularlyuseful means of excluding ischemia as a cause of prolonged chest pain

in patients with a non-diagnostic electrocardiogram

Initial therapy for acute coronary syndromes

All patients should be given oxygen and an aspirin tablet to chew.Morphine is an extremely effective agent to relieve the pain of acutemyocardial ischemia and MI; in addition, because morphine dilatesvenous capacitance vessels, it also relieves symptoms of pulmonarycongestion or edema Beyond this, the initial management of patientswith suspected ACS depends on the presenting electrocardiogram(Figure 6.6) Patients with ST-segment elevation are directed toimmediate reperfusion therapy, whereas those without ST-segmentelevation are treated initially with antiplatelet and antithrombotictherapy, and aggressive antianginal medical therapy to minimizeischemia

ST-elevation MI Serial ECGs and cardiac markers

Consider ETT for selected patients

Failure Success Rescue PCI

Aspirin Heparin (either UFH or LMWH)

β -Blocker GPllb/llla inhibitors for selected patients Nitrates for angina

Long term therapy Aspirin

β -Blockers ACE inhibitors Statins Clopidogrel?

Figure 6.6 An algorithm for the diagnosis and management of suspected acute coronar y syndromes (ACS) Dark boxes indicate diagnostic categories; white boxes indicate diagnostic or therapeutic procedures; and gray boxes indicate interpretation of tests or procedures * New, or presumed new left bundle branch block should be considered together with ST elevation †Intravenous unfractionated heparin is not indicated as adjunctive therapy with streptokinase ACE, angiotensin- conver ting enzyme; ECG, electrocardiogram; ETT, exercise tolerance test; GP, glycoprotein; LMWH, low molecular weight heparin; MI, myocardial infarction; PCI, percutaneous coronar y inter vention; UFH, unfractionated heparin

elevation myocardial infarction

Options for reperfusion therapy include fibrinolytic therapy andprimary percutaneous coronary intervention (PCI), either withpercutaneous transluminal coronary angioplasty or intracoronarystenting Primary PCI is the preferred method in centers with sufficientresources and expertise to perform successful PCI within 90 min ofpresentation to the hospital; however, if the “door to balloon” time isgreater than 90 min, then fibrinolytic therapy is preferred Clinicalstudies suggest that mortality is slightly lower with primary PCI thanwith pharmacologic reperfusion therapy when PCI is performed inexpert institutions In addition, recurrent MI and intracranialhemorrhage are observed less frequently with primary PCI than withfibrinolytic therapy

Because of resource limitations, fibrinolytic therapy is much morewidely available than PCI, and is the reperfusion method of choice inthe majority of hospitals The speed at which reperfusion therapy isadministered is much more important than the choice between PCIand fibrinolytic therapy, or the choice between individual fibrinolyticagents For each hour earlier that reperfusion therapy is administered,there is an absolute 1% decrease in mortality.9 All of the fibrinolyticagents currently available are plasminogen activators Reteplase(recombinant plasminogen activator [rPA]) and tenecteplase have aprolonged half-life and can be given as a bolus injection, as comparedwith the prolonged infusion required with alteplase (recombinanttissue plasminogen activator [tPA]) and streptokinase Because tPA,rPA, and tenecteplase are more potent than streptokinase, they areassociated with slightly lower mortality at a cost of slightly increasedbleeding The cost/benefit ratio favors these agents over streptokinase

in patients presenting early after symptom onset with a large area ofinjury (for example acute anterior MI) and a low risk for intracranialhemorrhage In groups with smaller potential for survival benefitand a greater risk for intracranial hemorrhage, streptokinase may bethe agent of choice, particularly in view of the cost Additionalconsiderations include avoiding readministration of streptokinase oranistreplase to patients for at least 4 years (preferably indefinitely)because of a high prevalence of potentially neutralizing antibodies,and because there is a risk of anaphylaxis upon re-exposure to thesedrugs

There are contraindications to fibrinolytic therapy (Table 6.2) Inaddition, fibrinolytic therapy is not indicated for patients with non-ST-segment elevation ACS because it increases bleeding complicationswithout a measurable clinical benefit.10

Antiplatelet and antithrombotic therapy

For patients with both ST-segment elevation and non-ST-segmentelevation ACS, aspirin reduces mortality, recurrent ischemia, and MI,and therefore should be given to all patients.11If a true aspirin allergy

is present, then clopidogrel may serve as an effective alternative.For patients with ST-segment elevation MI, intravenousunfractionated heparin (UFH) should be administered as an adjunct toreperfusion therapy with tPA, rPA, and tenecteplase With streptokinase,

on the other hand, there is no clear benefit of adjunctive heparin, and itshould not be given routinely In non-ST-segment elevation ACS, theaddition of intravenous UFH to aspirin reduces the rate of death andrecurrent infarction,12 and therefore should be given unless there is ableeding contraindication or the patient has a history of heparinassociated thrombocytopenia Heparin should be administered as aweight adjusted bolus and infusion, and titrated to a partialthromboplastin time of approximately 2 ×control

Recently, several novel antiplatelet and antithrombotic therapieshave been introduced that appear to be beneficial in patients withnon-ST-segment elevation ACS Ticlopidine and clopidogrel arethienopyridine agents that block adenosine diphosphate mediatedplatelet aggregation, and appear to provide protection similar to thatwith aspirin in patients with established vascular disease.13Clopidogrel causes fewer hematologic side effects than doesticlopidine, and thus is the agent of choice in this drug class Thecombination of clopidogrel and aspirin has recently been shown to beeven more beneficial than either agent alone, and prolonged therapywith these two agents following ACS will probably becomecommonplace in the near future

Glycoprotein IIb/IIIa inhibitors are intravenous compounds that blockthe final common pathway of platelet aggregation, namely fibrinogenmediated cross-linking at the glycoprotein IIb/IIIa receptor These agents

Table 6.2 Contraindications to thrombolytic therapy

Absolute contraindications Relative contraindications Active internal bleeding Blood pressure consistently Prior intracranial hemorrhage >180/110 mmHg

Stroke within past year Stroke or TIA at any time in past Recent head trauma or brain neoplasm Known bleeding diathesis Suspected aor tic dissection Proliferative diabetic retinopathy Major surger y or trauma within 2 weeks Prolonged CPR

Pregnancy CPR, cardiopulmonar y resuscitation; TIA, transient ischemic attack

aspirin or clopidogrel Two of the glycoprotein IIb/IIIa inhibitors,namely tirofiban and eptifibatide, have been shown to reduce theprobability of recurrent ischemic events among patients with non-ST-segment elevation ACS The benefit of these agents is greatest in highrisk patients (those with dynamic ST changes or elevated cardiacenzymes) who are managed with an early aggressive strategy, includingroutine angiography and percutaneous revascularization.14,15

Low molecular weight heparins (LMWHs) are created bydepolymerization of standard UFH and selection of those fragmentswith lower molecular weight LMWH is active early in the clottingcascade, inhibiting factor Xa to a greater extent than does UFH, therebyinhibiting both thrombin activity and its generation The highbioavailability and reproducible anticoagulant response of LMWHallows for subcutaneous administration without monitoring of theanticoagulant effect In high-risk patients with non-ST-segmentelevation ACS, the LMWH heparin compound enoxaparin is associatedwith modestly lower risk for death and MI versus UFH.16Other LMWHcompounds appear to be roughly equivalent to UFH Predominantlybecause of its ease of use, it is likely that LMWH will replace UFH formost patients with non-ST-segment elevation ACS in the near future

ββ -Blockers

β-Blockers exert their beneficial effect in ACS by decreasingmyocardial contractility and especially heart rate, thereby improvingthe balance between oxygen supply and demand As such, they mayreduce infarction size and lower short-term mortality rates Inaddition, β-blockers prevent atrial and ventricular arrhythmias inpatients following MI, and may prevent ventricular rupture followingtransmural MI Long-term therapy is indicated with β-blockersfollowing ACS to prevent recurrent infarction

Angiotensin-converting enzyme inhibitors

Angiotensin-converting enzyme (ACE) inhibitors have become amainstay in the treatment of patients with all types of ACS FollowingST-segment elevation MI, ACE inhibitors are administered because theyprevent deleterious left ventricular chamber remodeling and subsequentheart failure.17 In addition, long-term therapy with ACE inhibitorsprevents ischemic events in patients with established coronary arterydisease.18 ACE inhibitors should be initiated early (but not emergently)after the presentation of ACS and continued indefinitely

Nitrates favorably effect both myocardial oxygen supply anddemand, and thus are of particular value early in ACS Nitrates dilateboth normal and atherosclerotic resistance coronary arteries, andredistribute blood flow from epicardial to ischemic endocardial regions.Central venodilatation and modest peripheral arterial dilatation reducemyocardial oxygen demand Nitrates are effective in relievingsymptoms of ischemia in patients with ACS, and may be particularlyuseful in patients with concomitant congestive heart failure (CHF)because of the venodilating properties of this class of drugs In unstablepatients intravenous nitroglycerin should be given because it is easilytitratable and rapidly reversible In more stable patients topical or oralnitrates are usually adequate It is reasonable to use nitroglycerin for thefirst 24–48 hours in patients with ACS and recurrent ischemia, CHF, orhypertension Long-term nitrate therapy should only be used inpatients with ongoing symptoms of ischemia because there is noevidence that chronic nitrate therapy prevents MI or death

Calcium channel blockers

Calcium channel blockers have a limited role in the contemporarymanagement of ACS Unlike β-blockers and ACE inhibitors, thecalcium channel blockers have not been shown to reduce mortality.Thus, they should only be used for patients with contraindications orintolerance to β-blockers and ACE inhibitors, or if refractoryhypertension or tachycardia is present In patients with non-ST-segment elevation ACS diltiazem and verapamil may reduce recurrentischemia and infarction, but these agents are harmful for patientswith left ventricular dysfunction or clinical heart failure.Dihydropyridine calcium channel blockers such as nifedipine shouldnot be used in patients with ACS unless a β-blocker is used incombination to prevent reflex tachycardia Because of safetyconcerns, short-acting preparations of nifedipine should not be used

In-hospital management

Risk stratification

Risk stratification in ACS begins at the moment a patient arrives in theemergency room and should continue through hospital discharge andbeyond When the patient is first seen, history, physical examination,electrocardiogram, and serum marker information are rapidly

for adverse outcome Older age, presence of diabetes, three or more riskfactors, and a history of prior MI or CHF are all associated with increasedrisk In addition, tachycardia or bradycardia, hypotension, and evidencefor CHF are markers of increased risk that are easily obtained from afocused examination The electrocardiogram provides incrementalprognostic value An anterior location of infarction (or an inferiorinfarction with right ventricular extension or anterior ST depression),and a greater amount of ST deviation are associated with larger MI andincreased risk Finally, elevated serum cardiac markers at presentationand ACS despite aspirin use during the past week are associated with anincreased risk for morbidity and mortality.

Patients are initially triaged based on the presence or absence ofST-segment elevation on the presenting electrocardiogram (seeFigure 6.6) Subsequent risk stratification steps should focus onidentifying patients at risk for electrical, mechanical, and ischemiccomplications (see Figure 6.6), and on selecting those patients who willbenefit most from particular therapies, such as revascularization Itshould be remembered that with many therapies absolute risk reduction

is highest in those patients at greatest risk; therefore, the higher the risk

in an individual patient, the more aggressive the care should be

Left ventricular function

Left ventricular function is the single most important determinant

of long-term survival in patients with coronary artery disease Because

of the importance of left ventricular function to risk assessment, mostpatients should have an ejection fraction measurement following anacute MI Because reversible left ventricular dysfunction may follow

an ischemic insult (myocardial “stunning”), initial measurementsmay significantly underestimate true left ventricular function.Therefore, unless clinically indicated because of CHF, suspectedvalvular heart disease, or pericardial effusion, measurement ofejection fraction can be deferred until approximately 5–7 days afterthe MI Although echocardiography, contrast ventriculography, andradionuclide angiography are all reliable methods for assessing leftventricular ejection fraction, echocardiography has the advantage ofproviding structural information as well

Coronary angiography and revascularization

Routine adjunctive percutaneous coronary intervention followingfibrinolysis has not been shown to improve clinical outcomes

However, selected patients with ST-segment elevation MI should bemanaged with an early invasive strategy, including routinecatheterization and revascularization if the coronary anatomy issuitable Urgent catheterization is indicated for patients withcardiogenic shock and those with evidence of failed fibrinolysis (i.e.those without resolution of ST elevation 90–180 min after fibrinolytictherapy) Elective catheterization should be considered for patients athigh risk, including those with significant left ventricular dysfunctionand those with spontaneous ischemia or ischemia that is inducible on

a predischarge exercise test

Patients with non-ST-segment elevation ACS have lower initialmortality rates than do patients with ST-segment elevation MI, buthave higher rates of recurrent ischemia and reinfarction, so that at theend of 1 year outcomes are similar There has been considerablecontroversy as to whether an early invasive or early conservativemanagement strategy is preferred for patients with non-ST-segmentelevation ACS Recent studies suggest that in the moderninterventional era, with the use of coronary stents, glycoproteinIIb/IIIa inhibitors, low molecular weight heparins, and carefulattention to groin hemostasis, an early invasive approach is associatedwith modestly lower rates of recurrent ischemic events (MI andrecurrent ischemia) but not mortality In addition to preventingmorbidity, an early invasive approach may shorten the hospital stayand is not associated with excess overall costs The advantages of anearly invasive approach appear to be limited to patients atintermediate or high risk for ischemic complications, such as thosewith dynamic electrocardiographic changes and those with elevation

in cardiac enzymes

A more conservative approach utilizing vigorous medical therapymay be appropriate in low risk patients, especially those who havenever previously received antianginal medication After a “cool-off”period with antiplatelet and antithrombotic therapy, treadmillexercise testing with or without adjunctive imaging may help todefine patient management further If the pattern of angina remainsunstable or if electrocardiographic changes suggest ongoing ischemia,then coronary angiography is warranted In addition, significantischemia on the predischarge exercise test is considered an indicationfor coronary angiography and revascularization

Risk factor modification

Because hospitalization for an ACS is such a significant event in thelife of a patient, the hospital stay presents a unique opportunity toaddress lifestyle factors that contribute to the development and

progression of coronary atherosclerosis (Table 6.3) Smoking cessationand weight loss should be emphasized, and patients can begin cardiacrehabilitation before leaving the hospital Treatment of diabetes andhypertension should be optimized Most importantly, lipid loweringtherapy should be initiated for virtually all patients with ACS,regardless of low-density lipoprotein level Although diet (either a lowfat, low cholesterol diet, or a Mediterranean diet) should be instituted,the benefit of statin therapy has been unequivocally demonstrated

in patients with established coronary artery disease; therefore, statinsare the agents of choice for treating hyperlipidemia following ACS(Table 6.4)

Complications of acute myocardial infarction

The mechanical and electrical complications of acute MI aresummarized in Tables 6.5 and 6.6, respectively

Infarct expansion and remodeling

Following a large MI, the infarct area may expand and causethinning of the necrotic myocardium Over weeks to months, the leftventricular cavity may enlarge and assume a more globular shape.This process is termed left ventricular remodeling, and frequentlyleads to clinical congestive heart failure Angiotensin-converting

syndromes

Risk factor Goal of therapy Treatment options

Smoking Permanent smoking Behavioral therapy;

cessation pharmacotherapy; hypnosis Obesity BMI <25 kg/m 2 Diet; exercise; anorexigen

drug therapy as last resor t Diabetes Hemoglobin A1C<7·0% Insulin; oral sulfonylureas;

metformin; insulin sensitizing agents; diet Hyper tension Blood pressure Drug therapy; diet; exercise

<130/85 mmHg Hyperlipidemia LDL <100 mg/dl Drug therapy with statins

(<2·6 mmol/l) or fibrates; low fat, low

cholesterol, or Mediterranean diet BMI, body mass index; LDL, low-density lipoprotein

enzyme inhibitors have been shown to prevent adverse ventricularremodeling after MI.

Recurrent ischemia and infarction

Even when fibrinolytic therapy has been successful, reocclusion ofthe infarct artery may occur in up to 10–15% of patients by hospital

Table 6.4 Summary of treatments for patients with acute coronary syndromes

ST-segment Non-ST-segment Treatment elevation MI elevation ACS Comments

symptoms Antiplatelet therapy

aspirin Glycoprotein IIb/IIIa ++ +++ Most effective in

undergoing PCI Antithrombotic therapy

in high risk patients Reper fusion therapy

Fibrinolytic therapy ++++ NO

asthma or bradycardia ACE inhibitors ++++ +++ Avoid in severe

(<125 mg/dl) Therapies with a greater number of “ + ” signs are of greater value CHF, congestive hear t failure; LDL, low-density lipoprotein; PCI, percutaneous coronar y inter vention; SK, streptokinase; UFH, unfractionated heparin

Clinical Risk of death Complication presentation from complication Therapy

repeat fibrinolytic therapy

Cardiogenic shock CHF; hypotension; Ver y high Emergent PCI; IABP;

Right ventricular MI Hypotension with Moderate Early reper fusion;

in V4R Free wall rupture Tamponade; >90% Emergent surger y

surger y

Pericarditis Pleuritic/positional pain Low Aspirin

CHF, congestive hear t failure; JVD, jugular venous distension; PCI, percutaneous coronar y inter vention; IABP, intra-aor tic balloon pump

Table 6.6 Electrical complications of acute myocardial infarction

Ventricular tachycardia/fibrillation

Within first 24–48 hours Good Immediate cardioversion;

lidocaine; β -blockers After 48 hours Poor Immediate cardioversion;

electrophysiology study/ implantable defibrillator; amiodarone

Sinus bradycardia Excellent Atropine for hypotension

or symptoms Second-degree hear t block

Mobitz type I (Wenkebach) Excellent Atropine for hypotension

or symptoms Mobitz type II Guarded Temporar y pacemaker Complete hear t block

Inferior myocardial infarction Good Temporar y pacemaker Anterior myocardial infarction Poor Temporar y pacemaker

followed by permanent pacemaker

discharge and 30% of patients by 3 months; this complication isassociated with recurrent infarction in approximately 50% of casesand a twofold to threefold increase in mortality Reocclusion ratesafter primary percutaneous transluminal coronary angioplasty arealso high, but this complication may be reduced by the use ofadjunctive stenting and glycoprotein IIb/IIIa inhibition Recurrentischemia, without infarction, is also a frequent complicationfollowing MI Because patients with postinfarction angina are at highrisk for recurrent MI, cardiac catheterization should be considered.

Cardiogenic shock

Infarction of 40% or more of the left ventricle is associated with thedevelopment of cardiogenic shock Other, less common causes ofcardiogenic shock include septal rupture, free wall rupture, acutemitral regurgitation, and right ventricular infarction Cardiogenicshock is characterized by tissue hypoperfusion, hypotension, lowcardiac output, and elevated intracardiac filling pressures Even in themodern era the prognosis of cardiogenic shock is dismal, withmortality rates in excess of 70% Given the poor prognosis ofcardiogenic shock, early aggressive care is indicated Invasivehemodynamic monitoring with a Swan–Ganz catheter can help toconfirm the etiology of shock in difficult cases, and to tailorappropriate inotropic and vasodilator therapy The intra-aorticballoon pump has been used with success in patients with cardiogenicshock following MI; this device is of particular value in patients withmechanical complications such as acute mitral regurgitation or septalrupture The intra-aortic balloon pump augments cardiac output bycreating a low resistance zone for left ventricular outflow, andenhances coronary blood flow by inflating during diastole andincreasing coronary perfusion pressure

Dobutamine is the preferred inotropic agent for patients withcardiogenic shock This intravenous inotropic agent has activity atboth the β1- and β2-adrenergic receptors, and causes increased cardiaccontractility, increased heart rate, and (at high doses) peripheralvasoconstriction Intravenous vasodilators such as nitroprusside andnitroglycerin may also be used to reduce systemic vascular resistanceand increase cardiac output, provided the patient has sufficient bloodpressure to tolerate these agents

Unfortunately, although the treatments described above forcardiogenic shock may help to stabilize the patient, they have not beenshown to improve survival Early revascularization, on the other hand,does appear to improve survival in selected patients Emergentpercutaneous coronary intervention is clearly superior to thrombolytic

appropriately equipped, emergent catheterization and revascularizationare the treatments of choice In other centers, consideration should begiven to placement of an intra-aortic balloon pump and transfer to acenter that can perform urgent percutaneous coronary intervention.

Right ventricular myocardial infarction

Right ventricular infarction is a frequent complication of inferior wall

MI, and is almost always caused by proximal occlusion of the rightcoronary artery The diagnosis should be suspected in patients withinferior wall MI and unsuspected hypotension, particularly when itoccurs after small doses of nitrates Patients usually will have jugularvenous distension, but the lungs will be clear unless significant leftventricular infarction is present as well A right sided electrocardiogramshould be performed in all patients with inferior wall MI; ST-segmentelevation of 0·1 mV or more in V4R is sensitive and specific for thediagnosis of right ventricular infarction (Figure 6.7) The hemodynamicprofile of right ventricular infarction includes elevated right sidedfilling pressures with reduced cardiac output, findings similar to those

of pericardial tamponade In patients without electrocardiographicevidence of right ventricular infarction, therefore, echocardiography (orplacement of a pulmonary artery catheter) is indicated to distinguishbetween these two diagnoses

The hemodynamic derangements of right ventricular infarction can

be improved by administration of intravenous fluids such as normalsaline; many liters of fluid may be required to achieve hemodynamicstability Short-term morbidity and mortality are increased in patientswith right ventricular MI as compared with those with inferior wall

MI alone, but in patients who stabilize the prognosis for full recovery

of right ventricular function is good

Free wall rupture

Rupture of the left ventricular free wall is the most catastrophicmechanical complication of acute MI, with mortality rates greaterthan 90% Patients present with pericardial tamponade andcardiogenic shock, and the terminal rhythm is usually pulselesselectrical activity Incomplete free wall rupture can lead to formation

of a pseudoaneurysm In this situation, the rupture site is sealed byhematoma and the pericardium itself, and when the thrombusorganizes a pseudoaneurysm cavity is formed In contrast to a trueaneurysm, in which the wall is composed of myocardial tissue, the

wall of the pseudoaneurysm is composed of thrombus andpericardium but no myocardial tissue.

Septal rupture

Rupture of the interventricular septum causes an acute ventricularseptal defect, with left to right flow across the defect (Figure 6.8).19Congestive heart failure usually develops over hours to days(depending on the size of the defect), associated with a harshholosystolic murmur that may resemble the murmur of acute mitralregurgitation Either Doppler echocardiography or insertion of apulmonary artery catheter can be used to confirm the diagnosis If asignificant increase (“step-up”) in the oxygen saturation is seenbetween the right atrium and the right ventricle, then the presence ofventricular septal defect is likely

Acute mitral regurgitation

Acute mitral regurgitation following acute MI is caused by ischemicdysfunction or frank rupture of a papillary muscle This complication

is more common following inferior MI because the posteromedialpapillary muscle typically has a single blood supply from the rightcoronary artery, whereas the anterolateral papillary muscle has dualsupply from the left anterior descending and circumflex arteries Asopposed to cardiac rupture, this complication can occur with

of right ventricular involvement

relatively small, but well localized, infarctions The presentation issimilar to septal rupture, with a new holosystolic murmur classicallypresent in the setting of acute pulmonary edema and cardiogenicshock As blood pressure falls, the murmur may disappear entirely.Doppler echocardiography is particularly helpful in distinguishingbetween acute mitral regurgitation and septal rupture.

Ventricular tachycardia and ventricular fibrillation

Ventricular tachycardia is common in patients during the firsthours and days after MI, and does not appear to increase the risk formortality if the arrhythmia is rapidly terminated Ventriculartachycardia occurring after 24–48 hours, however, is associated with amarked increase in mortality Monomorphic ventricular tachycardia isusually due to a re-entrant focus around a scar, whereas polymorphicventricular tachycardia is more commonly a function of underlyingischemia, electrolyte abnormalities, or drug effects

Ventricular fibrillation is felt to be the primary mechanism ofarrhythmic sudden death In patients with acute MI, the vast majority

Figure 6.8 Ventricular septal rupture complicating acute myocardial infarction Four chamber echocardiographic view demonstrating color flow traversing across the ventricular septal defect (VSD) from the left ventricle (LV) to the right ventricle (RV) From Armstrong and Feigenbaum 19

of episodes of ventricular fibrillation occur early (<4–12 hours) afterinfarction Similar to sustained ventricular tachycardia, lateventricular fibrillation occurs more frequently in patients with severeleft ventricular dysfunction or congestive heart failure, and isassociated with a poor prognosis Patients with ventricularfibrillation, or sustained ventricular tachycardia associated withsymptoms or hemodynamic compromise should be cardiovertedemergently Underlying metabolic and electrolyte abnormalities must

be corrected, and ongoing ischemia should be treated Lidocaineremains effective for the treatment of symptomatic ventriculartachycardia or ventricular fibrillation, but should rarely be used as aprophylactic measure Intravenous amiodarone may be a particularlyeffective antiarrhythmic agent in the setting of acute MI because italso has antianginal properties

Bradyarrhythmias

Bradyarrhythmias are common following acute MI, and may be dueeither to increased vagal tone or to ischemia/infarction of conductiontissue Sinus bradycardia and Mobitz type I (Wenkebach) second-degree atrioventricular block are usually the result of stimulation ofcardiac vagal receptors on the inferoposterior surface of the leftventricle As a result, these generally benign rhythms are seen mostoften with inferior MI If severe bradycardia is seen (heart rate

<40–50 beats/min) or if bradycardia leads to hypotension, thenintravenous atropine should be given Temporary pacing is rarelyrequired unless there is hemodynamic or electrical instability Incontrast to Mobitz type I block, Mobitz type II block is seen lessfrequently but can progress suddenly to complete heart block;therefore, a temporary pacemaker should be inserted

Compete heart block following MI is an indication for a temporarypacemaker The long-term implications of complete heart block depend

on the infarct location With inferior MI the effect is usually transient,and so a permanent pacemaker is rarely required With anterior MIcomplete heart block is usually due to extensive infarction that involvesthe bundle branches, and as a result the atrioventricular block is usuallypermanent Mortality is extremely high, and permanent pacing should

be performed unless there are contraindications

Left ventricular aneurysm

A true left ventricular aneurysm is a discrete “out pouching” of

a thinned, dyskinetic, myocardial segment As opposed to a

pseudoaneurysm, the wall of a true aneurysm contains cardiac andfibrous tissues, the neck is broad based, and the risk for rupture issmall Although rupture is rare, aneurysms are still associated withincreased morbidity and mortality The dyskinetic aneurysm segment

is frequently lined with thrombus and may be a source for arterialembolus; in addition, the scarred aneurysm tissue may be a source formalignant ventricular arrhythmias Long-term oral anticoagulation

is often indicated to prevent mural thrombus and systemicembolization, but surgery is only indicated for intractable congestiveheart failure or arrhythmias

Left ventricular mural thrombus

Left ventricular mural thrombus occurs in approximately 40% ofpatients with Q-wave anterior MI Although echocardiography candetect mural thrombus in many cases (Figure 6.9),19patients with largeanterior MI remain at risk for systemic embolization even if nothrombus is seen Intravenous heparin, followed by coumadin for3–6 months, is indicated to prevent embolic complications in patientswith large anterior MI who are candidates for long-term anticoagulation

Figure 6.9 Mural thrombus complicating acute anterior myocardial infarction Four chamber echocardiographic view showing the mural thrombus delineated by arrows LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle From Armstrong and Feigenbaum 19

Fibrinous pericarditis may occur in the first few weeks followingtransmural infarction, and is often confused with recurrent angina orinfarction The pain of pericarditis is usually pleuritic, positional, andoften radiates to the shoulder A pericardial friction rub may bepresent Aspirin should be given, but non-steroidal anti-inflammatoryagents should be avoided because they may prevent normal healing

of the infarct Patients with Dressler’s syndrome have pericardial pain,generalized malaise, fever, elevated white blood cell count, elevatederythrocyte sedimentation rate, and pericardial effusion Thissyndrome occurs several weeks to several months following MI and isfelt to be immunologically mediated

Case studies

Case 6.1

A 75-year-old man presents to the hospital complaining of 2 hours

of severe substernal chest discomfort, radiating to the jaw The painbegan while the patient was lying in bed, and has been unrelieved bythree sublingual nitroglycerin tablets He feels nauseous andlightheaded, but is not dyspneic

Examination Physical examination: the patient appeared

diaphoretic lying flat in bed No abnormalities of skin, nail beds, ororal mucosa Pulse: 36 beats/min Blood pressure: 88/50 mmHg inright arm Jugular venous pulse: 12 cm Cardiac impulse: normal Firstheart sound: normal Second heart sound: split normally oninspiration No added sounds or murmurs Chest examination:normal air entry, no rales or rhonchi Abdominal examination: Softabdomen, no tenderness, and no masses Normal liver span Noperipheral edema Femoral, popliteal, posterior tibial, and dorsalispedis pulses: all normal volume and equal Extremities: all cool.Carotid pulses: normal, no bruits Optic fundi: normal

Investigations His electrocardiogram is shown in Figure 6.10.

advanced age, prior coronary disease, and low blood pressure.(E) Activated platelets play a critical role in the pathophysiology

of this disorder

2 Which of the following therapies would not be appropriate forthis patient? (A) Immediate reperfusion therapy with primarypercutaneous coronary intervention or fibrinolytic therapy (B)Aspirin (C) Intravenous unfractionated heparin (D) Intravenous

β-blocker (E) Temporary ventricular pacing

3 Which of the following diagnostic tests should not be performedroutinely in this patient? (A) Serial measurement of cardiac enzymes.(B) A right sided electrocardiogram to assess for the possibility ofright ventricular infarction (C) Coronary angiography followingfibrinolytic therapy (D) Echocardiography (E) Measurement offasting lipids

4 Following placement of a transcutaneous pacemaker, the patient

is administered fibrinolytic therapy and becomes free of chestpain 60 min later, with a stable heart rate and blood pressure Sixhours later, the patient develops severe dyspnea Physicalexamination at that time reveals wet rales three-quarters of theway up both lung fields, and a new holosystolic murmur at theleft lower sternal border Which of the following complicationsare most likely? (A) Ventricular free wall rupture with pericardialtamponade (B) Ventricular pseudoaneurysm (C) Rupture of theinterventricular septum with creation of an acute ventricularseptal defect (D) Acute mitral regurgitation due to papillarymuscle ischemia or infarction (E) Either C or D

aVR

aVL II

5 Which of the following tests or procedures is indicated to diagnoseand treat this patient? (A) Doppler echocardiography (B)Placement of a pulmonary artery catheter to measure oxygensaturations in the right atrium and right ventricle (C) Placement

of an intra-aortic balloon pump (D) Urgent surgery (E) All of theabove

Answers

Answer to question 1 C ST-segment elevation MI is caused bycomplete thrombotic occlusion of an epicardial coronary artery,whereas subtotal occlusion typically leads to non-ST-segmentelevation ACS For this reason, fibrinolytic therapy is beneficial inpatients with ST-segment elevation MI but not in those with non-ST-segment elevation ACS

Answer to question 2 D The rhythm demonstrated on theelectrocardiogram is complete heart block In the setting of inferior

MI, this is likely to be due to reflex increase in vagal tone or ischemia

to the atrioventrciular node Temporary pacing is indicated but thepatient is unlikely to require placement of a permanent pacemaker.With anterior MI, the prognosis of complete heart block is much moreominous β-Blockers are contraindicated because they further blockatrioventricular nodal function

Answer to question 3 C Serial cardiac enzymes should be measured

to confirm the diagnosis of myocardial infarction, to assess infarctsize, and to monitor the success of reperfusion therapy A right sidedelectrocardiogram is indicated for all patients with inferior MI toassess for right ventricular involvement This patient has clear lungsand elevated jugular venous pressure, which are suggestive of rightventricular infarct Routine assessment of left ventricular functionshould be performed after MI, but in stable patients this measurementcan wait for around 5–7 days to minimize the effects of “stunning” onthe measurement of left ventricular function Measurement of fastinglipids should be performed to identify which patients should betreated with statins Following successful fibrinolysis, routinecoronary angiography is not indicated unless patients have significantleft ventricular dysfunction, recurrent ischemia, or a positivepredischarge exercise test

Answer to question 4 E The clinical presentation of acute congestiveheart failure and a new holosystolic murmur suggests either acutemitral regurgitation or a ventricular septal defect Ventricular free wall

pseudoaneurysm is usually noticed incidentally during cardiacimaging procedures.

Answer to question 5 E – all of the above Doppler echocardiography

is the simplest technique to distinguish between acute mitralregurgitation and ventricular septal defect (see Figure 6.8) In addition,

a significant increase in the oxygen saturation between the rightatrium and right ventricle suggests that oxygenated blood is movingfrom the left ventricle to the right ventricle across a ventricular septaldefect Placement of an intra-aortic balloon pump may be a lifesavingmeasure to stabilize patients with these complications while a surgicalteam is mobilized

Case 6.2

A 71-year-old woman has had intermittent chest discomfort for

3 days While watching her grandson’s graduation she develops severeresting chest pain that lasts for several hours, and she is now short ofbreath Her past history is significant for hypertension and non-insulin-dependent diabetes, and she has smoked cigarettes for many years

Examination Physical examination: the patient appeared to be

suffering significant pain Pulse: 114 beats/min, regular Blood pressure:170/95 mmHg in right arm Respiratory rate: 28/min Jugular venouspulse: 8 cm Cardiac impulse: normal First heart sound: normal.Second heart sound: split normally on inspiration Third heart soundpresent Chest examination: rales one-quarter of the way up the lungfields Abdominal examination: soft abdomen, no tenderness, and nomasses Normal liver span No peripheral edema Femoral, popliteal,posterior tibial, and dorsalis pedis pulses: all normal volume andequal Carotid pulses: normal, no bruits Optic fundi: normal

Investigations Her admission electrocardiogram demonstrates

1·5 mm ST depressions in leads V2–V6

Questions

1 Which of the following therapies is not indicated at this time?(A) Intravenous β-blockers (B) Oral diltiazem (C) Intravenousmorphine (D) A chewed aspirin (E) Low molecular weight heparin

2 Following the initiation of aspirin, low molecular weight heparin,

β-blockers, and nitroglycerin, the patient becomes pain-freeand the ST depressions resolve Cardiac enzymes are sent from asample of blood collected 8 hours after the onset of chest pain

Which of the following statements are true? (A) An elevatedcreatinine kinase (CK)-MB or troponin T would suggest adiagnosis of non-ST-segment elevation myocardial infarction (B)

If the enzymes are elevated then no further testing for cardiacmarkers should be performed (C) There is no need to checkcardiac enzymes because the diagnosis of ACS is already knownfrom the history and electrocardiography (D) At this time point,

8 hours after the onset of symptoms, one would expectmyoglobin but not CK-MB or troponin to be elevated (E) If thetroponin is elevated but CK-MB is normal, then this suggests thatthe troponin elevation is a “false positive”

3 The CK-MB is elevated to three times the upper limit of normal,and cardiac troponin I is elevated to 10 times the upper limit ofnormal The patient has three further episodes of chest pain onmedical therapy Which of the following statements about an earlyinvasive (cardiac catheterization and revascularization) versusearly conservative (medical therapy with catheterization reservedfor treatment failures) strategy is true for this patient? (A) Because

of the patient’s advanced age and female sex, an early conservativestrategy is preferable (B) An early invasive strategy is indicated forall patients with suspected ACS (C) The patient is at high risk foradverse events because of her advanced age, ST changes, elevatedcardiac markers, the presence of congestive heart failure, andrecurrent ischemic symptoms, and an early invasive strategy islikely to be beneficial (D) The patient should be treated with aglycoprotein IIb/IIIa inhibitor and, if she has no further episodes

of chest pain, discharged home (E) Statin therapy is not indicated

if she is managed with an invasive approach

Answers

Answer to question 1 B Aspirin, β-blockers, and heparin (eitherunfractionated heparin or low molecular weight heparin) areindicated as initial therapy for this patient with non-ST-segmentelevation ACS Morphine would be expected to be particularlyeffective in relieving both chest pain and dyspnea Diltiazem iscontraindicated in the presence of congestive heart failure

Answer to question 2 A Elevated cardiac biomarkers in the setting oftypical anginal pain and dynamic ST changes are diagnostic of non-ST-segment elevation MI However, it is still important to performserial measurements to confirm a typical rise and fall in the cardiacmarker curve so that accurate timing of the infarct can be performed.This is particularly important in patients who have stuttering chestpain over several days, such as the one discussed here Although the

biomarker elevation is important for prognostic purposes and to helpselect between therapies At 8 hours, one would expect all of themarkers (myoglobin, CK-MB, and troponins T and I) to be elevated(see Figure 6.5) Finally, low level troponin elevations in the absence

of CK-MB elevation are indicative of microinfarction and areassociated with an increased risk for adverse events

Answer to question 3 C Although controversy exists as to thesuperiority of an early invasive or early conservative approach in non-ST-segment elevation ACS, for patients at high risk an early invasiveapproach is generally preferred Elderly women frequently receive lessintensive care, despite the fact that they may be at particularly high risk.Glycoprotein IIb/IIIa inhibitors are most beneficial when combined with

an early invasive approach Finally, statin therapy is clearly indicated forpatients following revascularization Figure 6.3 shows an angiogram that

is representative of non-ST-segment elevation ACS

3 de Lemos JA, Cannon CP Stone PH Acute myocardial infarction In: Rosendorff C,

ed Essential cardiology Philadelphia: WB Saunders, 2001:463–501.

4 Davies MJ The pathophysiology of acute coronary syndromes Heart 2000;83:

361–6.

5 Antman EM, Braunwald E Acute myocardial infarction In: Braunwald E, Libby P,

Zipes D, eds Heart disease A textbook of cardiovascular medicine, 6th ed Philadelphia:

W.B Saunders Company, 2001:1114–218.

6 Antman EM General hospital management In: Julian DG, Braunwald E, eds.

Management of acute myocardial infarction London: W.B Saunders Ltd., 1994:29–70.

7 Antman EM, Tanasijevic MJ, Thompson B, et al Cardiac-specific troponin I levels

to predict the risk of mortality in patients with acute coronary syndromes N Engl

J Med 1996;335:1342–9.

8 Wu A Cardiac markers Totowa: Humana Press Inc., 1998.

9 Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials

of more than 1000 patients Lancet 1994;343:311–22.

10 The TIMI-IIIB Investigators Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and

non-Q-wave myocardial infarction Results of the TIMI IIIB trial Circulation

13 CAPRIE Steering Committee A randomised, blinded, trial of clopidogrel versus

aspirin in patients at risk of ischaemic events (CAPRIE) Lancet 1996;348:1329–39.

14 The PRISM-PLUS Trial Investigators Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction.

N Engl J Med 1998;338:1488–97.

15 The Pursuit Trial Investigators Inhibition of platelet glycoprotein IIb/IIIa with

eptifibatide in patients with acute coronary syndromes N Engl J Med 1998;339:

436–43.

16 Antman EM, Cohen M, Radley D, et al Assessment of the treatment effect of

enoxaparin for unstable angina/non-Q-wave myocardial infarction TIMI

11B-ESSENCE meta-analysis Circulation 1999;100:1602–8.

17 ACE Inhibitor Myocardial Infarction Collaborative Group Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic

overview of individual data from 100,000 patients in randomized trials Circulation

19 Armstrong WF, Feigenbaum H Echocardiography In: Braunwald E, Libby P,

Zipes D, eds Heart disease: a textbook of cardiovascular medicine, 6th ed Philadelphia:

W.B Saunders Company, 2001:160–236.

RAO H NASEEM, MICHAEL L MAIN,

JOHN D RUTHERFORD

During myocardial ischemia an imbalance occurs between myocardialoxygen supply and demand Because the heart is an aerobic organ andrelies almost exclusively on oxidation of substrates for the generation

of energy, it can develop only a small oxygen debt The oxygen supply

to the myocardial cells falls, with anaerobic glycolysis and lactateproduction The common clinical symptom associated with anaerobicmetabolism is an uncomfortable sensation in the chest, usuallybrought on by effort, called angina pectoris

Myocardial oxygen supply

Supply of oxygen to the myocardium depends on the oxygencarrying capacity of the blood and the rate of coronary blood flow.Oxygen carrying capacity of the blood is determined by thehemoglobin content and systemic oxygenation, and in the absence ofanemia or lung disease it remains fairly constant

Coronary artery blood flow is determined by the perfusion pressureinto the artery and the resistance to flow by the vessel Coronaryblood flow (CBF) is directly proportional to the perfusion pressure (P)and is inversely proportional to coronary vascular resistance (R; CBF =

P/R) The systolic flow of blood in the coronary arteries is reduced bycompression of the contracting myocardium Therefore, the coronaryarteries have maximal flow during diastole, and the perfusion pressure

is approximately the aortic diastolic pressure

In the coronary circulation the major resistance to flow comes fromthe resistance arterioles, in accordance with Poiseuille’s law, whichstates that resistance increases by a power of four as the vessel radiusdecreases The large conductance arteries (epicardial arteries) governthe quantity of blood arriving at the resistance vessels Coronaryvascular resistance is modified by extravascular compressive forces,autoregulation, metabolic regulation, neural and neurotransmittercontrol, as well as humoral endothelial factors

Myocardial oxygen demand

The three major determinants of myocardial oxygen consumption

of Laplace, which states that in a case of an idealized thin wallspherical shell:

Wall stress = (P ×r)/2hwhere P is the transmural pressure, r is radius of the sphere, and h isthe wall thickness Increased left ventricular filling (for examplevolume overload states such as mitral or aortic regurgitation)increases the ventricular radius, raises the wall tension, and thusoxygen consumption Conversely, any physiologic or pharmacologicmaneuver that decreases left ventricular filling and size (for exampleblood loss, nitrate therapy) decreases wall tension and myocardialoxygen consumption Circumstances that increase pressure in the leftventricle (aortic stenosis, hypertension) increase wall tension, andconditions that decrease ventricular pressure reduce it (vasodilatortherapy) Finally, wall tension is inversely proportional to ventricularwall thickness In a hypertrophied heart the force is spreadthroughout a greater mass that has a lower wall tension, and oxygenconsumption per gram of tissue is less than in a heart with thin walls.Therefore, when ventricular hypertrophy develops (for examplechronic pressure overload of aortic stenosis), it can serve acompensatory role in reducing oxygen consumption

Heart rate is a very important determinant of myocardial oxygendemand As heart rate increases, the number of cardiac contractionsand the amount of adenosine triphosphate (ATP) consumed per minincreases, and oxygen requirements rise Conversely, slowing heartrate (for example, with β-blocker therapy) reduces ATP utilizationand oxygen consumption Following an inotropic stimulus, thechange in myocardial oxygen consumption depends on the extent towhich wall tension is reduced (as a consequence of reduction

in heart size) and the degree of augmentation of contractility

contractility will elevate myocardial oxygen consumption becauseheart size, and therefore wall tension, are not reduced substantiallyand do not offset the influence of increased contractility Negativeinotropic agents such as β-blockers may decrease myocardial oxygenconsumption.

Angina

History

Heberden’s initial description of angina being accompanied by “asense of strangling and anxiety” is still relevant, although otheradjectives are frequently used to describe this distress, including

“vice-like”, “suffocating”, “crushing”, “heavy”, and “squeezing” Thepatient may not interpret these symptoms as pain The site of thediscomfort is usually retrosternal, but radiation of the discomfortoften occurs and is usually projected to the left shoulder, neck, jaw,and ulnar distribution of the left arm Radiation to the same areas onthe right side and to the epigastric area also occurs Less commonly,pain is referred to the left scapular region of the back

Typically angina pectoris begins gradually, and reaches a maximumintensity over a period of minutes before dissipating It is usuallyprovoked by activity and is relieved within minutes by rest or use ofnitroglycerin Patients with angina prefer to pause, rest, sit, or stopwalking during episodes Angina may be precipitated by less activityfollowing a large meal or by cold weather Severity of angina is assessed

by the circumstances associated with its occurrence (Table 7.1).1Characteristics that are not suggestive of angina are fleeting,momentary chest pains described as “needle jabs” or “sharp pains”;discomfort that is aggravated or precipitated by breathing, or by asingle movement of the trunk or arm; or a pain that is localized to avery small area, or that is reproduced by pressure on the chest wall

A careful history should uncover risk factors that predispose tocoronary artery disease In general, angina pectoris will tend to occur

in males who are older than 40 years and females older than 50 years,

a history of cigarette smoking is common, and the presence ofdiabetes mellitus, hypertension, hypercholesterolemia, or peripheralarterial disease is highly relevant (Table 7.2).2Similarly, a prior history

of myocardial infarction, or a family history of myocardial infarction

or sudden death in a male parent or sibling before 55 years, or afemale parent or sibling before 65 years is very important

Physical examination

Inspection

Inspection of the eyes may reveal a corneal arcus (the size of a cornealarcus appears to correlate positively with age and levels of cholesteroland low-density lipoproteins), and examination of the skin may showxanthomas (cholesterol-filled nodules), which are found eithersubcutaneously or over tendons in patients with hyperlipoproteinemia.Eruptive xanthomas are tiny yellowish nodules that are 1–2 mm indiameter on an erythematous base, which may occur anywhere onthe body and are found in association with hyperchylomicronemiaand therefore in patients with type 1 hyperlipoproteinemia (familialhyperchylomicronemia) and type 5 hyperlipoproteinemia (severeelevation in triglyceride levels associated with obesity, a fat-rich diet,and poorly controlled diabetes) Patients with xanthoma tendinosum

Table 7.1 Severity of angina (Canadian Cardiovascular Society)

Angina class Features

I Angina does not occur with ordinar y physical activity.

Angina occurs only with strenuous or prolonged exer tion

II Slight limitation in ordinar y activity Angina occurs with

rapid walking on level ground or up inclines or steps

III Marked limitation of ordinar y physical activity Angina

occurs when walking

IV Inability to carr y out even mild physical activity without

angina, which also may occur briefly at rest From Campeau 1

Table 7.2 Pretest likelihood of coronary artery disease according to age, sex, and symptoms

No symptoms Non-anginal pain

surfaces to the hands, and Achilles’ tendons) usually have type 2hyperlipoproteinemia (genetic disorder of low-density lipoproteins).

Blood pressure

Blood pressure may be chronically elevated or may rise acutely(along with heart rate) during an angina attack Changes in bloodpressure may precede (and precipitate) or follow (and be caused by)angina

Pulses

Patients with arterial disease may exhibit abnormalities of thearterial pulses (diminished or absent radial, brachial, carotid, femoral,popliteal, dorsalis, or posterior tibial pulses), bruits of the carotids orabdomen, or a palpable abdominal aortic aneurysm

Auscultation

A fourth heart sound (generated when augmented atrialcontraction generates presystolic ventricular distension) can be seenwith left ventricular hypertrophy of aortic stenosis or systemichypertension A fourth heart sound can also be associated withmyocardial ischemia (during angina or acute myocardial infarction)because the atrial “booster pump” is needed to help fill the relativelystiff, ischemic ventricle Evidence of cardiac failure may be found withelevation in jugular venous pressure, a chest examination revealingrales, an enlarged or congested liver, and the presence of peripheraledema

The resting electrocardiogram is normal in approximately half

of patients with chronic angina pectoris The most commonabnormalities are non-specific ST-T changes with, or without,evidence of prior transmural myocardial infarction manifested bypathologic Q waves Conduction disturbances such as left bundlebranch block, or left anterior fascicular block, can be seen in patientswith chronic stable angina and may suggest impairment in leftventricular function reflecting multivessel disease and priormyocardial damage Left ventricular hypertrophy on theelectrocardiogram in patients with chronic stable angina usuallysuggests the presence of underlying hypertension

Diagnosis of coronary artery disease

Bayes’ theorem

Bayes’ theorem describes a method of calculating probabilities, and

in clinical cardiology the method is used routinely during stresstesting analyses.3The pretest likelihood of coronary artery disease in

an individual being tested, and the sensitivity and specificity of theless than perfect stress test being used are incorporated into a post-testprobability of coronary artery disease being present Therefore, non-invasive procedures that are used to try to detect coronary arterydisease yield probability estimates of the presence of disease ratherthan a categorical “yes or no” answer

• There is a large discrepancy in the predictive value of stress tests insymptomatic versus asymptomatic subjects In an asymptomatic50-year-old male a “positive” electrocardiographic exercise stresstest result consisting of 1 mm ST-segment depression has a verylow probability of being associated with coronary artery disease.However, a “positive” result consisting of symptoms typical ofangina and ST-segment depression of 2 mm or greater has a veryhigh probability of reflecting coronary artery disease.

• Bayes’ theorem indicates that, although the reliability of a lessthan perfect test is defined by sensitivity and specificity, a testcannot be adequately interpreted without reference to theprevalence of disease in the population under study (pretestlikelihood of disease) Details of the history, including theenvironment or country of origin, age, history of myocardialinfarction, history of cigarette smoking, elevated cholesterol, andthe presence (or absence) of electrocardiographic Q wavesindicating prior infarction, all help to define the pretest probability

of disease

• In a given population, a finite proportion of normal persons,defined by test specificity, will manifest an abnormal (falsepositive) response Therefore, the predictive value of a positive test

is diminished in part by the proportion of normal subjects in thepopulation being studied (Table 7.3).3

• The pretest likelihood of coronary artery disease changesdramatically according to age, sex, and symptoms (see Table 7.2)

• A negative test has a low predictive value in a population with highprevalence of disease, whereas it has a high predictive value in apopulation with low prevalence of disease

• Changes that develop during a stress test do not provide a “yes orno” statement regarding the presence of coronary artery disease,but rather provide a probability based on a continuum of risk

Stress testing

Exercise electrocardiogram

In a patient with a chest pain syndrome the monitoring ofsymptoms and recording of electrocardiograms during and afterexercise is useful for assessing the probability of the presencesignificant of coronary artery disease The presence of a criticalobstruction in one or more coronary arteries is suggested by certain