Chapter 50Chapter 50ST-Elevation Myocardial Infarction: Pathology, ST-Elevation Myocardial Infarction: Pathology,

Pathophysiology, and Clinic FeaturesPathophysiology, and Clinic Features

Vinod PatelVinod Patel

University of South FloridaUniversity of South Florida

The The pathological pathological diagnosis of myocardial infarction (MI) diagnosis of myocardial infarction (MI) requires evidence of myocyte cell death as a consequence of requires evidence of myocyte cell death as a consequence of prolonged ischemia. prolonged ischemia.

The The clinical clinical diagnosis of MI requires an integrated assessment diagnosis of MI requires an integrated assessment of the history with some combination of indirect evidence of of the history with some combination of indirect evidence of myocardial necrosis using biochemical, electrocardiographic, myocardial necrosis using biochemical, electrocardiographic, and imaging modalities. and imaging modalities.

Typical rise and/or fall of biochemical markers of myocardial Typical rise and/or fall of biochemical markers of myocardial necrosis with at least one of the following:   necrosis with at least one of the following:   

• a)    Ischemic symptoms   a)    Ischemic symptoms   

• b)    Development of pathologic Q waves in the ECG   b)    Development of pathologic Q waves in the ECG   

• c)    ECG changes indicative of ischemia (ST segment c)    ECG changes indicative of ischemia (ST segment elevation or depression)   elevation or depression)   

• d)    Imaging evidence of new loss of viable myocardium d)    Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. or new regional wall motion abnormality.

Pathologic findings of an acute myocardial infarction. Pathologic findings of an acute myocardial infarction.

Criteria for Healing or Healed Myocardial Infarction.Criteria for Healing or Healed Myocardial Infarction.Any one of the following criteria satisfies the diagnosis for Any one of the following criteria satisfies the diagnosis for healing or healed myocardial infarction:  healing or healed myocardial infarction:  • 1. Development of new pathological Q waves in serial 1. Development of new pathological Q waves in serial

ECGs. The patient may or may not remember previous ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis symptoms. Biochemical markers of myocardial necrosis may have normalized depending on the length of time that may have normalized depending on the length of time that has passed since the infarction developed.   has passed since the infarction developed.   

• 2. Pathological findings of a healed or healing infarction. 2. Pathological findings of a healed or healing infarction.

In the United States, nearly 1 million patients a year suffer In the United States, nearly 1 million patients a year suffer from an acute MI.from an acute MI.

More than 1 million patients with suspected acute MI are More than 1 million patients with suspected acute MI are admitted yearly to coronary care units in the United States.admitted yearly to coronary care units in the United States.

Of particular concern from a global perspective are Of particular concern from a global perspective are projections that the burden of disease in developing countries projections that the burden of disease in developing countries will become similar to those now afflicting developed will become similar to those now afflicting developed countries. countries.

Drop in mortality appears to result from a fall in the incidence Drop in mortality appears to result from a fall in the incidence of STEMI (replaced in part by an increase in the rate of of STEMI (replaced in part by an increase in the rate of unstable angina/non-ST-segment elevation MI and a fall in the unstable angina/non-ST-segment elevation MI and a fall in the case fatality rate once STEMI has occurred). case fatality rate once STEMI has occurred).

The short-term mortality rate of patients with STEMI in The short-term mortality rate of patients with STEMI in randomized trials is in the range of 6.5 to 7.5 %, whereas randomized trials is in the range of 6.5 to 7.5 %, whereas observational data bases suggest 5 to 20%observational data bases suggest 5 to 20%

Clinical trial data from studies of fibrinolysis show that the Clinical trial data from studies of fibrinolysis show that the elderly (75 years old or older) continue to suffer a mortality elderly (75 years old or older) continue to suffer a mortality rate four times that of younger patients. rate four times that of younger patients.

Variation has also been observed in the treatment patterns of Variation has also been observed in the treatment patterns of certain population subgroups with STEMI, notably women certain population subgroups with STEMI, notably women and blacks.and blacks.

Table 50.1Table 50.1

Causes of MI without coronary atherosclerosisCauses of MI without coronary atherosclerosis

    Arteritis   Arteritis   • Luetic   Luetic   • Granulomatous (Takayasu disease)   Granulomatous (Takayasu disease)   • Polyarteritis nodosa   Polyarteritis nodosa   • Mucocutaneous lymph node (Kawasaki) syndrome   Mucocutaneous lymph node (Kawasaki) syndrome   • Disseminated lupus erythematosus   Disseminated lupus erythematosus   • Rheumatoid spondylitis   Rheumatoid spondylitis   • Ankylosing spondylitis   Ankylosing spondylitis   

Trauma to coronary arteries   Trauma to coronary arteries   • Laceration   Laceration   • Thrombosis   Thrombosis   • Iatrogenic   Iatrogenic   • Radiation (radiation therapy for neoplasia) Radiation (radiation therapy for neoplasia)

Coronary mural thickening with metabolic disease or intimal Coronary mural thickening with metabolic disease or intimal proliferative disease   proliferative disease   • Mucopolysaccharidoses (Hurler disease)   Mucopolysaccharidoses (Hurler disease)   • Homocystinuria   Homocystinuria   • Fabry disease   Fabry disease   • Amyloidosis   Amyloidosis   • Juvenile intimal sclerosis (idiopathic arterial calcification Juvenile intimal sclerosis (idiopathic arterial calcification

of infancy)   of infancy)   • Intimal hyperplasia associated with contraceptive steroids Intimal hyperplasia associated with contraceptive steroids

or with the postpartum period   or with the postpartum period   • Pseudoxanthoma elasticum   Pseudoxanthoma elasticum   • Coronary fibrosis caused by radiation therapy Coronary fibrosis caused by radiation therapy

Luminal narrowing by other mechanisms Luminal narrowing by other mechanisms • Spasm of coronary arteries (Prinzmetal angina with normal Spasm of coronary arteries (Prinzmetal angina with normal

coronary arteries)   coronary arteries)   • Spasm after nitroglycerin withdrawal   Spasm after nitroglycerin withdrawal   • Dissection of the aorta   Dissection of the aorta   • Dissection of the coronary artery Dissection of the coronary artery

Emboli to Coronary Arteries  Emboli to Coronary Arteries  • Infective endocarditis   Infective endocarditis   • Nonbacterial thrombotic endocarditis   Nonbacterial thrombotic endocarditis   • Prolapse of mitral valve   Mural thrombus from left atrium, Prolapse of mitral valve   Mural thrombus from left atrium,

left ventricle, or pulmonary veins   left ventricle, or pulmonary veins   • Prosthetic valve emboli   Prosthetic valve emboli   • Cardiac myxoma   Cardiac myxoma   • Associated with cardiopulmonary bypass surgery and Associated with cardiopulmonary bypass surgery and

coronary arteriography   coronary arteriography   • Paradoxical emboli   Paradoxical emboli   • Papillary fibroelastoma of the aortic valve (fixed embolus) Papillary fibroelastoma of the aortic valve (fixed embolus)

    • Thrombi from intracardiac catheters or guidewiresThrombi from intracardiac catheters or guidewires

Congenital Coronary Artery Anomalies  Congenital Coronary Artery Anomalies  • Anomalous origin of left coronary from pulmonary artery   Anomalous origin of left coronary from pulmonary artery   • Left coronary artery from anterior sinus of Valsalva   Left coronary artery from anterior sinus of Valsalva   • Coronary arteriovenous and arteriocameral fistulas   Coronary arteriovenous and arteriocameral fistulas   • Coronary artery aneurysms Coronary artery aneurysms

Myocardial Oxygen Demand-Supply Disproportion  Myocardial Oxygen Demand-Supply Disproportion  • Aortic stenosisAortic stenosis• Incomplete differentiation of the aortic valve   Incomplete differentiation of the aortic valve   • Aortic insufficiency   Aortic insufficiency   • Carbon monoxide poisoning   Carbon monoxide poisoning   • Thyrotoxicosis   Thyrotoxicosis   • Prolonged hypotension   Prolonged hypotension   • Takotsubo cardiomyopathy Takotsubo cardiomyopathy

Hematological (in situ Thrombosis)  Hematological (in situ Thrombosis)  

• Polycythemia vera   Polycythemia vera   

• Thrombocytosis   Thrombocytosis   

• Disseminated intravascular coagulation   Disseminated intravascular coagulation   

• Hypercoagulability, thrombosis, thrombocytopenic purpura Hypercoagulability, thrombosis, thrombocytopenic purpura Miscellaneous  Miscellaneous  

• Cocaine abuse   Cocaine abuse   

• Myocardial contusion   Myocardial contusion   

• Myocardial infarction with normal coronary arteries   Myocardial infarction with normal coronary arteries   

• Complication of cardiac catheterization Complication of cardiac catheterization

PLAQUEPLAQUE

Release of chemokines by endothelial cells and increase Release of chemokines by endothelial cells and increase expression of adhesion proteins.expression of adhesion proteins.

Entry of WBC into the wall.Entry of WBC into the wall. T cells in the arterial wall produce cytokines which T cells in the arterial wall produce cytokines which

stimulates endothelial cell proliferation and activate stimulates endothelial cell proliferation and activate microphages.microphages.

Events During AtherogenesisEvents During Atherogenesis

At autopsy, the atherosclerotic plaques of patients who died of At autopsy, the atherosclerotic plaques of patients who died of STEMI are composed of :STEMI are composed of :

• 90% fibrous tissue of varying density and cellularity with 90% fibrous tissue of varying density and cellularity with superimposed thrombus. superimposed thrombus.

• 10% Calcium, lipid-laden foam cells, and extracellular 10% Calcium, lipid-laden foam cells, and extracellular lipid. lipid.

• The atherosclerotic plaques generally more complex and The atherosclerotic plaques generally more complex and irregular than those in vessels not associated with STEMI. irregular than those in vessels not associated with STEMI.

• Coronary arterial thrombi are approximately 1cm in length Coronary arterial thrombi are approximately 1cm in length in most cases; adhere to the luminal surface of an artery; in most cases; adhere to the luminal surface of an artery; and contain platelets, fibrin, erythrocytes, and leukocytes.and contain platelets, fibrin, erythrocytes, and leukocytes.

The balance of synthetic and degradative activity of collagen, the The balance of synthetic and degradative activity of collagen, the major structural component of the fibrous cap, account for its major structural component of the fibrous cap, account for its mechanical strength and determines plaque stability and prognosis.mechanical strength and determines plaque stability and prognosis.

Statins -> stabalize plaques by their lipid lowering effect as well as Statins -> stabalize plaques by their lipid lowering effect as well as reduce plaque inflammation. reduce plaque inflammation.

2/3 of the plaques resulting in STEMI are caused by an occlusion 2/3 of the plaques resulting in STEMI are caused by an occlusion of 50% or less and 85% has occlusion of <70% of 50% or less and 85% has occlusion of <70%

The coronary distribution of STEMI is:The coronary distribution of STEMI is:• LAD 40-50% RCA 30-40% Lcx 15-20%LAD 40-50% RCA 30-40% Lcx 15-20%

Vulnerable plaques Vulnerable plaques • Large area of foam cells and extracellular lipids Large area of foam cells and extracellular lipids • Thin fibrous cap Thin fibrous cap • Few smooth muscle Few smooth muscle • Clusters of inflammatory cellsClusters of inflammatory cells

Role of acute plaque changesRole of acute plaque changes• Rupture/fissuring: exposing the highly thrombogenic plaque Rupture/fissuring: exposing the highly thrombogenic plaque

constituents.constituents.• Erosion/ulceration: exposing the thrombogenic Erosion/ulceration: exposing the thrombogenic

subendothelial basement membrane to bloodsubendothelial basement membrane to blood• Hemorrhage into the atheroma, expending its volume.Hemorrhage into the atheroma, expending its volume.

Plaque fissuring and disruptionPlaque fissuring and disruption• Overexpression of metalloproteinase enzymes such as Overexpression of metalloproteinase enzymes such as

collagenase, gelatinase, and stromelysin collagenase, gelatinase, and stromelysin • Activated macrophages and mast cells abundant at the site.Activated macrophages and mast cells abundant at the site.• Stresses induced by intraluminal pressure, coronary Stresses induced by intraluminal pressure, coronary

vasomotor tone, tachycardia (cyclic stretching and vasomotor tone, tachycardia (cyclic stretching and compression), and disruption of nutrient vessels combine to compression), and disruption of nutrient vessels combine to produce plaque disruption. produce plaque disruption.

Junction of the fibrous cap and the adjacent normal plaque free Junction of the fibrous cap and the adjacent normal plaque free arterial segment is the location at which the blood flow-inducing arterial segment is the location at which the blood flow-inducing mechanical stresses within the plaque are highest and the fibrous mechanical stresses within the plaque are highest and the fibrous cap is thinnest.cap is thinnest.

A number of key physiological variables such as systolic A number of key physiological variables such as systolic blood pressure, heart rate, blood viscosity, endogenous tissue blood pressure, heart rate, blood viscosity, endogenous tissue plasminogen activator (t-PA) activity, plasminogen activator plasminogen activator (t-PA) activity, plasminogen activator inhibitor-1 (PAI-1) levels, plasma cortisol levels, and plasma inhibitor-1 (PAI-1) levels, plasma cortisol levels, and plasma epinephrine levels exhibit circadian and seasonal variations epinephrine levels exhibit circadian and seasonal variations and increase at times of stress. and increase at times of stress.

Vasospasm is caused by:Vasospasm is caused by:• Circulating adrenergic agonistsCirculating adrenergic agonists• Locally released platelet contentsLocally released platelet contents• Impaired secretion of endothelial cell relaxing factors Impaired secretion of endothelial cell relaxing factors

relative to contracting factors.relative to contracting factors.• Mediators released from peri-vascular inflammatory cells.Mediators released from peri-vascular inflammatory cells.

http://www.youtube.com/watch?v=41h8OhRHAw0http://www.youtube.com/watch?v=41h8OhRHAw0

Exposed to subendothelial collagen and necrotic plaque Exposed to subendothelial collagen and necrotic plaque contents, platelets undergo adhesion, aggregation, activation contents, platelets undergo adhesion, aggregation, activation and release of potent aggregators including TXA2, serotonin and release of potent aggregators including TXA2, serotonin and PF 3 -4and PF 3 -4

Activation of extrinsic pathway.Activation of extrinsic pathway.

RIGHT VENTRICULAR INFARCTION. RIGHT VENTRICULAR INFARCTION.

• Approximately 50% of patients with inferior infarction have Approximately 50% of patients with inferior infarction have some involvement of the right ventricle some involvement of the right ventricle

• RV occurs less commonly than would be anticipated from RV occurs less commonly than would be anticipated from the frequency of atherosclerotic lesions involving the RCA. the frequency of atherosclerotic lesions involving the RCA.

This discrepancy can probably be explained by the lower This discrepancy can probably be explained by the lower oxygen demands oxygen demands

Inter-coronary collateral system of the RV is richer than Inter-coronary collateral system of the RV is richer than that of the leftthat of the left

The thinness of the RV wall allows the chamber to derive The thinness of the RV wall allows the chamber to derive some nutrition from the blood within the RV cavity some nutrition from the blood within the RV cavity

ATRIAL INFARCTION. ATRIAL INFARCTION. This can be seen in up to 10% of patients with STEMI if PR-This can be seen in up to 10% of patients with STEMI if PR-

segment displacement is used as the criterion for atrial segment displacement is used as the criterion for atrial infarction. infarction.

Although isolated atrial infarction is observed in 3.5% of Although isolated atrial infarction is observed in 3.5% of autopsies of patients with STEMI, it often occurs in autopsies of patients with STEMI, it often occurs in conjunction with ventricular infarction. conjunction with ventricular infarction.

Occurs more frequently in the atrial appendages Occurs more frequently in the atrial appendages (Rt > Lt) explained by higher oxygen content of left atrial (Rt > Lt) explained by higher oxygen content of left atrial

blood. blood. It has also been linked to reduced secretion of atrial natriuretic It has also been linked to reduced secretion of atrial natriuretic

peptide and a low cardiac output syndrome when right peptide and a low cardiac output syndrome when right ventricular infarction coexists.ventricular infarction coexists.

No plaque disruption in about 10% of cases.No plaque disruption in about 10% of cases. Many of these cases are caused by coronary artery spasm Many of these cases are caused by coronary artery spasm

and/or thrombosis, perhaps with underlying endothelial and/or thrombosis, perhaps with underlying endothelial dysfunction or small plaques in apparent on coronary dysfunction or small plaques in apparent on coronary angiography. angiography.

MI with angiographically normal coronary vessels. MI with angiographically normal coronary vessels.

• Young Young

• Often have a history of cigarette smokingOften have a history of cigarette smoking (Takotsubo cardiomyopathy) catecholamine-mediated (Takotsubo cardiomyopathy) catecholamine-mediated

myocardial stunning and microvascular dysfunction play myocardial stunning and microvascular dysfunction play important roles.important roles.

Transmural versus subendocardial infractionTransmural versus subendocardial infraction Most MIs are transmuralMost MIs are transmural Subendocardial infarct constitutes an area limited to inner 1/3 Subendocardial infarct constitutes an area limited to inner 1/3

or ½.or ½.• Plaque disruption -> thrombus-> lysis before necrosis Plaque disruption -> thrombus-> lysis before necrosis

extends across major thickness.extends across major thickness.• Chronic occlusion + prolonged severe reduction in Chronic occlusion + prolonged severe reduction in

systemic blood pressure.systemic blood pressure.

Anaerobic glycolysisAnaerobic glycolysis Inadequate production of high-energy phosphates and Inadequate production of high-energy phosphates and

accumulation of potentially noxious breakdown products (such accumulation of potentially noxious breakdown products (such as lactic acid)as lactic acid)

Striking loss of contractility occurs with in 60 seconds. Striking loss of contractility occurs with in 60 seconds. Ultrasturctural evidence of irreversible myocyte injury.Ultrasturctural evidence of irreversible myocyte injury. Cell death: Cell death:

• Coagulation necrosisCoagulation necrosis

• ApotosisApotosis

Prior to cell death there is a period during which the ischemic Prior to cell death there is a period during which the ischemic myocyte is viable, but vulnerable to further injury if blood flow myocyte is viable, but vulnerable to further injury if blood flow is restored (ie, reperfusion injury). During this period, the is restored (ie, reperfusion injury). During this period, the reintroduction of oxygen and energy into an abnormal cellular reintroduction of oxygen and energy into an abnormal cellular environment triggers additional events that produce further environment triggers additional events that produce further myocyte damage.myocyte damage.

Reperfusion injury refers to myocardial, vascular, or Reperfusion injury refers to myocardial, vascular, or electrophysiological dysfunction that is induced by the electrophysiological dysfunction that is induced by the restoration of blood flow to previously ischemic tissue. restoration of blood flow to previously ischemic tissue. Manifestations include:Manifestations include:• Reperfusion arrhythmias Reperfusion arrhythmias • Endothelial cell damage leading to microvascular dysfunction Endothelial cell damage leading to microvascular dysfunction • Myocardial stunning Myocardial stunning • Myocyte death/ infarction Myocyte death/ infarction

Factors that contribute to reperfusion injury include the Factors that contribute to reperfusion injury include the following:following:• Damage to cellular and organelle membranes, including Damage to cellular and organelle membranes, including

mitochondria mitochondria • Myocyte hypercontracture Myocyte hypercontracture • Free radical formation Free radical formation • Aggregation of leukocytes and inflammatory mediators Aggregation of leukocytes and inflammatory mediators • Platelet activation Platelet activation • Complement activation Complement activation • Activation of the pro-apoptotic signaling cascade Activation of the pro-apoptotic signaling cascade • Endothelium damage and vasoconstriction Endothelium damage and vasoconstriction

Time Gross Feattures Light Microscopy

0-30 mins

None None

½- 4 hr None Waviness of fibers at borders

4-12 hr Occ dark mottling Coagulation necrosis, edema, hemorrhage

12-24 hr Dark mottling Ongoing necrosis, Contraction band, WBC infiltrate

1-3 days Mottling with yello-tan infarct center

WBC infiltrate

3-7 days Hyperemic border, central yellow-tan softening

Disintegration of myofibers, early phagocytosis of dead cells by macrophages at infract border

7-10 days

Maximally yello-tan and soft, with depressed red-tan margins

Phagocytosis in process and formation of fibrovascular granulation tissue at margins

10-14 days

Red-gray depressed infarct borders

Well established granulation tissue with new blood vessels and collagen deposition

2-8 wk Gray-white scar, progressive from border toward core of infarct

Increased collagen deposition with decreased cellularity

>2 months

Scarring complete Dense collagenous scar

Time Gross Feattures Electron Microscopy

0- ½ hr None Relaxation of myofibrils, glycogen loss, mitochondrial swelling.

½- 4 hr None Sarcolemmal disruption

The coronary collateral circulation is particularly well The coronary collateral circulation is particularly well developed in patients with developed in patients with

• Coronary occlusive disease, especially with the reduction Coronary occlusive disease, especially with the reduction of the luminal cross-sectional area by more than 75% in of the luminal cross-sectional area by more than 75% in one or more major vessels one or more major vessels

• Chronic hypoxia, as occurs in cases of severe anemia, Chronic hypoxia, as occurs in cases of severe anemia, chronic obstructive pulmonary disease, and cyanotic chronic obstructive pulmonary disease, and cyanotic congenital heart diseasecongenital heart disease

• Left ventricular hypertrophy.Left ventricular hypertrophy.

LV systolic functionLV systolic function

Four abnormal contraction patterns develop in sequence: Four abnormal contraction patterns develop in sequence: • 1. Dyssynchrony1. Dyssynchrony• 2. Hypokinesis 2. Hypokinesis • 3. Akinesis3. Akinesis• 4. Dyskinesis4. Dyskinesis

Hyperkinesis of the remaining normal myocardium initially Hyperkinesis of the remaining normal myocardium initially accompanies dysfunction of the infarcting segment.accompanies dysfunction of the infarcting segment.

Increased motion of the non-infarcted region subsides within 2 Increased motion of the non-infarcted region subsides within 2 weeks of infarction, during which time some degree of weeks of infarction, during which time some degree of recovery often occurs in the infarct region. recovery often occurs in the infarct region.

The degree to which end-systolic volume increases is perhaps The degree to which end-systolic volume increases is perhaps the most powerful hemodynamic predictor of mortality the most powerful hemodynamic predictor of mortality following STEMIfollowing STEMI

Ischemia at distance:Ischemia at distance:

Patients with STEMI often also show reduced myocardial Patients with STEMI often also show reduced myocardial contractile function in non-infarcted zonescontractile function in non-infarcted zones

This may result from previous obstruction of the coronary artery This may result from previous obstruction of the coronary artery supplying the non-infarcted region of the ventricle and loss of supplying the non-infarcted region of the ventricle and loss of collaterals from the freshly occluded infarct related vesselcollaterals from the freshly occluded infarct related vessel

Infarct extension:Infarct extension: As necrotic myocytes slip past each other, the infarct zone As necrotic myocytes slip past each other, the infarct zone

thins and elongates, especially in patients with large anterior thins and elongates, especially in patients with large anterior infarcts, leading to infarct expansion. infarcts, leading to infarct expansion.

Ventricular Dilatation:Ventricular Dilatation: As the ventricle dilates during the first few hours to days after As the ventricle dilates during the first few hours to days after

infarction, regional and global wall stress increases according infarction, regional and global wall stress increases according to Laplace's law. In some patients a vicious cycle of dilation to Laplace's law. In some patients a vicious cycle of dilation begetting further dilation ensues. The degree of ventricular begetting further dilation ensues. The degree of ventricular dilation, which depends closely on infarct size, patency of the dilation, which depends closely on infarct size, patency of the infarct-related artery, and activation of the renin-angiotensin-infarct-related artery, and activation of the renin-angiotensin-aldosterone system (RAAS), can be favorably modified by aldosterone system (RAAS), can be favorably modified by inhibitors of this system, even in the absence of symptomatic inhibitors of this system, even in the absence of symptomatic left ventricular dysfunction.left ventricular dysfunction.

Increasing stiffness in the infarcted zone of myocardium Increasing stiffness in the infarcted zone of myocardium improves left ventricular function because it prevents improves left ventricular function because it prevents paradoxical systolic wall motion (dyskinesia).paradoxical systolic wall motion (dyskinesia).

When the abnormally contracting segment exceeds 15%, the When the abnormally contracting segment exceeds 15%, the ejection fraction may decline and elevations of left ventricular ejection fraction may decline and elevations of left ventricular end-diastolic pressure and volume occur. end-diastolic pressure and volume occur.

Clinical heart failure accompanies areas of abnormal Clinical heart failure accompanies areas of abnormal contraction exceeding 25%. contraction exceeding 25%.

Cardiogenic shock, often fatal, accompanies loss of more than Cardiogenic shock, often fatal, accompanies loss of more than 40% of the left ventricular myocardium.40% of the left ventricular myocardium.

These alterations associate with a decrease in the peak rate of These alterations associate with a decrease in the peak rate of decline in LV pressure [peak (-)dP/dt], an increase in the time decline in LV pressure [peak (-)dP/dt], an increase in the time constant of the fall in LV pressure, and an initial rise in LV constant of the fall in LV pressure, and an initial rise in LV end-diastolic pressure. end-diastolic pressure.

Over several weeks, end-diastolic volume increases and Over several weeks, end-diastolic volume increases and diastolic pressure begins to fall toward normal. diastolic pressure begins to fall toward normal.

A marked depression of left ventricular stroke volume A marked depression of left ventricular stroke volume ultimately lowers aortic pressure and reduces coronary ultimately lowers aortic pressure and reduces coronary perfusion pressure; this condition may intensify myocardial perfusion pressure; this condition may intensify myocardial ischemia and thereby initiate a vicious circle. Systemic ischemia and thereby initiate a vicious circle. Systemic inflammation secondary to the infarction process leads to the inflammation secondary to the infarction process leads to the release of cytokines that contribute to vasodilation and a fall in release of cytokines that contribute to vasodilation and a fall in systemic vascular resistance.systemic vascular resistance.

The inability of the left ventricle to empty normally also leads The inability of the left ventricle to empty normally also leads to an increased preload; that is, it dilates the well-perfused, to an increased preload; that is, it dilates the well-perfused, normally functioning portion of the left ventricle.normally functioning portion of the left ventricle.

EFFECTS OF TREATMENT EFFECTS OF TREATMENT Glucocorticosteroids and NSAID can cause scar Glucocorticosteroids and NSAID can cause scar

thinning and greater infarct expansion, thinning and greater infarct expansion, RAAS inhibitors attenuate ventricular enlargement + RAAS inhibitors attenuate ventricular enlargement +

attenuation of endothelial dysfunction + direct attenuation of endothelial dysfunction + direct antiatherogenic effects.antiatherogenic effects.

Inhibition of aldosterone action reduces collagen Inhibition of aldosterone action reduces collagen deposition and decreases the development of ventricular deposition and decreases the development of ventricular arrhythmias. arrhythmias.

Pathophysiology of other organ systemsPathophysiology of other organ systems PULMONARYPULMONARY

• An inverse relationship exists between arterial oxygen tension An inverse relationship exists between arterial oxygen tension and pulmonary artery diastolic pressure and pulmonary artery diastolic pressure

• widespread closure of small, dependent airways during the first widespread closure of small, dependent airways during the first 3 days after STEMI. 3 days after STEMI.

• Virtually all lung volume indices—total lung capacity, Virtually all lung volume indices—total lung capacity, functional residual capacity, and residual volume, as well as functional residual capacity, and residual volume, as well as vital capacity—fall during STEMI. These reductions correlate vital capacity—fall during STEMI. These reductions correlate with the elevations of left-sided filling pressures and are most with the elevations of left-sided filling pressures and are most probably caused by increases in pulmonary extravascular water. probably caused by increases in pulmonary extravascular water.

• REDUCTION OF AFFINITY OF HEMOGLOBIN FOR REDUCTION OF AFFINITY OF HEMOGLOBIN FOR OXYGEN. OXYGEN.

Increase 2,3 DPG -> Increase in P50Increase 2,3 DPG -> Increase in P50 18 percent increase in oxygen release from oxyhemoglobin 18 percent increase in oxygen release from oxyhemoglobin

in patients with cardiogenic shock.in patients with cardiogenic shock.

PANCREAS. • Glucose appears to be a more favorable energy source than

free fatty acids for the ischemic myocardium by permitting ATP generation by anaerobic glycolysis.

• Hyperglycemia and impaired glucose tolerance are common in patients with STEMI.

• As a consequence of splanchnic vasoconstriction accompanying severe left ventricular failure, abnormalities in insulin secretion occur.

• In addition, increased activity of the sympathetic nervous system with augmented circulating catecholamines inhibits insulin secretion and augments glycogenolysis, also contributing to the elevation of blood sugar.

ADRENAL MEDULLA. ADRENAL MEDULLA. • The plasma and urinary catecholamine levels peak during The plasma and urinary catecholamine levels peak during

the first 24 hours with the greatest rise in plasma the first 24 hours with the greatest rise in plasma catecholamine secretion occurring during the first hour. catecholamine secretion occurring during the first hour.

• Serious arrhythmias and result in an increase in myocardial Serious arrhythmias and result in an increase in myocardial oxygen consumption, both directly and indirectly, as a oxygen consumption, both directly and indirectly, as a consequence of catecholamine-induced elevation of consequence of catecholamine-induced elevation of circulating free fatty acids. circulating free fatty acids.

• Circulating catecholamines enhance platelet aggregationCirculating catecholamines enhance platelet aggregation• Hyper catecholamine state is a foundation for beta-Hyper catecholamine state is a foundation for beta-

adrenergic receptor blocker regimens in the acute phase.adrenergic receptor blocker regimens in the acute phase.

ACTIVATION OF THE RENIN-ANGIOTENSIN-ACTIVATION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM. ALDOSTERONE SYSTEM. • Both locally and systemically generated angiotensin II can Both locally and systemically generated angiotensin II can

stimulate the production of various growth factors, such as stimulate the production of various growth factors, such as platelet-derived growth factor and transforming growth platelet-derived growth factor and transforming growth factor-beta, that promote compensatory hypertrophy in the factor-beta, that promote compensatory hypertrophy in the noninfarcted myocardium, as well as control the structure noninfarcted myocardium, as well as control the structure and tone of the infarct-related coronary and other and tone of the infarct-related coronary and other myocardial vessels.myocardial vessels.

• Angiotensin II also causes release of endothelin, PAI-1, Angiotensin II also causes release of endothelin, PAI-1, and aldosterone, which may cause vasoconstriction, and aldosterone, which may cause vasoconstriction, impaired fibrinolysis, and increased sodium retention, impaired fibrinolysis, and increased sodium retention, respectively.respectively.

ADRENAL CORTEX. ADRENAL CORTEX.

• Plasma and urinary 17-hydroxycorticosteroids and Plasma and urinary 17-hydroxycorticosteroids and ketosteroids, as well as aldosterone, rise markedly in ketosteroids, as well as aldosterone, rise markedly in patients with STEMI. patients with STEMI.

• The magnitude of the elevation of cortisol correlates with The magnitude of the elevation of cortisol correlates with

infarct size and mortality.infarct size and mortality.

NATRIURETIC PEPTIDES NATRIURETIC PEPTIDES

• Released early after STEMI, peaking at about 16 hours. Released early after STEMI, peaking at about 16 hours.

• Originate both from the infarcted myocardium, as well as Originate both from the infarcted myocardium, as well as viable noninfarcted myocardiumviable noninfarcted myocardium

• Correlates with infarct size and regional wall motion Correlates with infarct size and regional wall motion abnormalitiesabnormalities

• Conversely, patients with persistently elevated levels at 3 Conversely, patients with persistently elevated levels at 3 to 4 weeks after STEMI have an increased risk of cardiac-to 4 weeks after STEMI have an increased risk of cardiac-related mortality over the ensuing 5 to 10 years.related mortality over the ensuing 5 to 10 years.

THYROID GLAND. THYROID GLAND.

• Transient decrease in serum tri-iodothyronine (T3) levels, a Transient decrease in serum tri-iodothyronine (T3) levels, a fall that is most marked on about the third day after the fall that is most marked on about the third day after the infarct. infarct.

• Variable changes or no change in thyroxine (T4) and Variable changes or no change in thyroxine (T4) and thyroid-stimulating hormone (TSH) levels. thyroid-stimulating hormone (TSH) levels.

RENAL FUNCTION RENAL FUNCTION

• Prerenal azotemia and acute renal failure can complicate Prerenal azotemia and acute renal failure can complicate cardiogenic shock. cardiogenic shock.

• Increase in circulating atrial natriuretic peptide play a role Increase in circulating atrial natriuretic peptide play a role in the hypotension that accompanies right ventricular in the hypotension that accompanies right ventricular infarction.infarction.

PLATLETS:PLATLETS:

• Circulating platelets are hyper-aggregable in patients with Circulating platelets are hyper-aggregable in patients with STEMI. Platelets from STEMI patients have an increased STEMI. Platelets from STEMI patients have an increased propensity for aggregation locally in the area of a disrupted propensity for aggregation locally in the area of a disrupted plaque and also release vasoactive substances.plaque and also release vasoactive substances.

HEMOSTATIC MARKERS. HEMOSTATIC MARKERS. • Elevated serum fibrinogen degradation productsElevated serum fibrinogen degradation products• Platelet factor 4 and beta-thromboglobulin Platelet factor 4 and beta-thromboglobulin • Fibrinopeptide A, a protein released from fibrin by Fibrinopeptide A, a protein released from fibrin by

thrombin, is a marker of ongoing thrombosis and is thrombin, is a marker of ongoing thrombosis and is increased during the early hours of STEMI. increased during the early hours of STEMI.

• Interpretation of the coagulation tests may be complicated Interpretation of the coagulation tests may be complicated by elevated blood levels of catecholamines, concomitant by elevated blood levels of catecholamines, concomitant shock, and/or pulmonary embolism, conditions that are all shock, and/or pulmonary embolism, conditions that are all capable of altering various tests of platelet and coagulation capable of altering various tests of platelet and coagulation function and use of antithrombotic agents.function and use of antithrombotic agents.

LEUKOCYTES. LEUKOCYTES.

• Leukocytosis usually accompanies STEMI in proportion to Leukocytosis usually accompanies STEMI in proportion to the magnitude of the necrotic process, elevated the magnitude of the necrotic process, elevated glucocorticoid levels, and possibly inflammation in the glucocorticoid levels, and possibly inflammation in the coronary arteries. coronary arteries.

• The magnitude of elevation of the leukocyte count The magnitude of elevation of the leukocyte count associates with in-hospital mortality after STEMI.associates with in-hospital mortality after STEMI.

BLOOD VISCOSITY. BLOOD VISCOSITY. • Increase in blood viscosity is due to hemoconcentration in Increase in blood viscosity is due to hemoconcentration in

the first few days after infarction.the first few days after infarction.• Elevated serum concentrations of alpha2-globulin and Elevated serum concentrations of alpha2-globulin and

fibrinogen, components of the acute phase response to fibrinogen, components of the acute phase response to tissue necrosis responsible for late increases.tissue necrosis responsible for late increases.

CLINICAL FEATURES CLINICAL FEATURES

Predisposing Factors: Predisposing Factors: • Heavy exercise (particularly in fatigued or habitually Heavy exercise (particularly in fatigued or habitually

inactive patients) and emotional stress can precipitate inactive patients) and emotional stress can precipitate STEMI.STEMI.

• Noncardiac surgical procedures , hypotension (e.g., Noncardiac surgical procedures , hypotension (e.g., hemorrhagic or septic shock) and increased myocardial hemorrhagic or septic shock) and increased myocardial oxygen demands caused by aortic stenosis, fever, oxygen demands caused by aortic stenosis, fever, tachycardia, and agitation can also be responsible for tachycardia, and agitation can also be responsible for myocardial necrosis. myocardial necrosis.

• Rarely, munition workers exposed to high concentrations Rarely, munition workers exposed to high concentrations of nitroglycerin develop MI when they are withdrawn from of nitroglycerin develop MI when they are withdrawn from this exposure, suggesting that it is caused by vasospasm.this exposure, suggesting that it is caused by vasospasm.

CIRCADIAN PERIODICITY. CIRCADIAN PERIODICITY.

• Peak incidence of events between 6 am and noon Peak incidence of events between 6 am and noon associated with rises in plasma catecholamines and cortisol associated with rises in plasma catecholamines and cortisol and increases in platelet aggregabilityand increases in platelet aggregability. .

• Circadian peak is absent in patients receiving beta blocker Circadian peak is absent in patients receiving beta blocker or aspirin before their presentation with STEMI.. or aspirin before their presentation with STEMI..

Ischemic cascade outlining the Sequence of events:Ischemic cascade outlining the Sequence of events:

• Perfusion AbnormalityPerfusion Abnormality

• Diastolic DysfunctionDiastolic Dysfunction

• Abnormal DTI/ Strain (Systolic)Abnormal DTI/ Strain (Systolic)

• Visibly Abnormal Wall MotionVisibly Abnormal Wall Motion

• ECG changesECG changes

• AnginaAngina

• Infraction/scarInfraction/scar

HISTORYHISTORY PRODROMAL SYMPTOMS. PRODROMAL SYMPTOMS. A feeling of general malaise or frank exhaustion often A feeling of general malaise or frank exhaustion often

accompanies other symptoms preceding STEMI. accompanies other symptoms preceding STEMI. Women may present differently than men.Women may present differently than men.

NATURE OF THE PAIN. NATURE OF THE PAIN. • The pain is prolonged, usually lasting for more than 30 The pain is prolonged, usually lasting for more than 30

minutes and frequently for a number of hours. minutes and frequently for a number of hours. • In patients with preexisting angina pectoris, the pain of In patients with preexisting angina pectoris, the pain of

infarction usually resembles that of angina with respect to infarction usually resembles that of angina with respect to location. However, it is generally much more severe, lasts location. However, it is generally much more severe, lasts longer, and is not relieved by rest and nitroglycerin.longer, and is not relieved by rest and nitroglycerin.

• Both angina pectoris and the pain of STEMI are thought to Both angina pectoris and the pain of STEMI are thought to arise from nerve endings in ischemic or injured, but not arise from nerve endings in ischemic or injured, but not necrotic myocardium. necrotic myocardium.

GI SYMPTOMS. GI SYMPTOMS. • Nausea and vomiting may occur, presumably because of Nausea and vomiting may occur, presumably because of

activation of the vagal reflex or effects of opiates if used. activation of the vagal reflex or effects of opiates if used. • Occasionally, a patient complains of diarrhea or a violent Occasionally, a patient complains of diarrhea or a violent

urge to defecate during the acute phase of STEMI. Other urge to defecate during the acute phase of STEMI. Other symptoms include feelings of profound weakness, symptoms include feelings of profound weakness, dizziness, palpitations, cold perspiration, and a sense of dizziness, palpitations, cold perspiration, and a sense of impending doom. impending doom.

SILENT STEMI SILENT STEMI ATYPICAL PRESENTATIONATYPICAL PRESENTATION

• Heart failure Heart failure • Classic angina pectoris without a particularly severe or prolonged Classic angina pectoris without a particularly severe or prolonged

episode episode • Atypical location of the pain Atypical location of the pain • Central nervous system manifestations, resembling those of stroke, Central nervous system manifestations, resembling those of stroke,

secondary to a sharp reduction in cardiac output in a patient with secondary to a sharp reduction in cardiac output in a patient with cerebral arteriosclerosiscerebral arteriosclerosis

• Apprehension and nervousnessApprehension and nervousness• Sudden mania or psychosisSudden mania or psychosis• SyncopeSyncope• Overwhelming weaknessOverwhelming weakness• Acute indigestion and Acute indigestion and • Peripheral embolization. Peripheral embolization.

GENERAL APPEARANCE. GENERAL APPEARANCE. • Cool and clammy SkinCool and clammy Skin• Bluish or mottled color over the extremitiesBluish or mottled color over the extremities• Marked facial pallor with severe cyanosis of the lips and Marked facial pallor with severe cyanosis of the lips and

nail bedsnail beds• Depending on the degree of cerebral perfusion, patient in Depending on the degree of cerebral perfusion, patient in

shock may converse normally or may evidence confusion shock may converse normally or may evidence confusion and disorientationand disorientation

HEART RATE. HEART RATE. • Marked bradycardia to a rapid regular or irregular Marked bradycardia to a rapid regular or irregular

tachycardia, depending on the underlying rhythm and the tachycardia, depending on the underlying rhythm and the degree of left ventricular failuredegree of left ventricular failure

BLOOD PRESSURE. BLOOD PRESSURE. • HTN among previously normoten-sive patients presumably HTN among previously normoten-sive patients presumably

as a consequence of adrenergic discharge.as a consequence of adrenergic discharge.• Normalization of BP in hypertensive patient after STEMI, Normalization of BP in hypertensive patient after STEMI,

eventually regain their elevated levels of blood pressure, eventually regain their elevated levels of blood pressure, generally 3 to 6 months after infarction. generally 3 to 6 months after infarction.

• Bezold-Jarisch reflex activation may also transiently have Bezold-Jarisch reflex activation may also transiently have systolic blood pressure below 90 mm Hg. Their systolic blood pressure below 90 mm Hg. Their hypotension eventually resolves spontaneously, although hypotension eventually resolves spontaneously, although the process can be accelerated by intravenous atropine (0.5 the process can be accelerated by intravenous atropine (0.5 to 1 mg) and assumption of the Trendelenburg position. to 1 mg) and assumption of the Trendelenburg position.

TEMPERATURE AND RESPIRATION. TEMPERATURE AND RESPIRATION. • Most patients with extensive STEMI develop fever, a Most patients with extensive STEMI develop fever, a

nonspecific response to tissue necrosis, within 24 to 48 nonspecific response to tissue necrosis, within 24 to 48 hours of the onset of infarction. hours of the onset of infarction.

• Fever usually resolves by the fourth or fifth day after Fever usually resolves by the fourth or fifth day after infarction.infarction.

JUGULAR VENOUS PULSE. JUGULAR VENOUS PULSE. • Right ventricular infarction (whether or not it accompanies Right ventricular infarction (whether or not it accompanies

left ventricular infarction) often results in marked jugular left ventricular infarction) often results in marked jugular venous distention and, when it is complicated by necrosis venous distention and, when it is complicated by necrosis or ischemia of right ventricular papillary muscles, tall or ischemia of right ventricular papillary muscles, tall c-vc-v waves of tricuspid regurgitation are evident.waves of tricuspid regurgitation are evident.

CAROTID PULSE. CAROTID PULSE. • A small pulse suggests a reduced stroke volume. A small pulse suggests a reduced stroke volume. • A sharp, brief upstroke is often observed in patients with A sharp, brief upstroke is often observed in patients with

mitral regurgitation or ruptured ventricular septum with a mitral regurgitation or ruptured ventricular septum with a left-to-right shunt. left-to-right shunt.

• Pulsus alternans reflects severe left ventricular dysfunction.Pulsus alternans reflects severe left ventricular dysfunction.

THE CHEST. THE CHEST. • Cough with hemoptysis, suggesting pulmonary embolism Cough with hemoptysis, suggesting pulmonary embolism

with infarction, can also occur. with infarction, can also occur. • Kilip classification (1967)Kilip classification (1967)

Class I patients are free of rales and a third heart sound. Class I patients are free of rales and a third heart sound. Class II patients have rales but only to a mild to Class II patients have rales but only to a mild to

moderate degree (<moderate degree (<50%50% of lung fields) and may or may of lung fields) and may or may not have an S3.not have an S3.

Class III have rales in more than half of each lung field Class III have rales in more than half of each lung field and frequently have pulmonary edema. and frequently have pulmonary edema.

Class IV patients are in cardiogenic shock.Class IV patients are in cardiogenic shock.

PALPATION. PALPATION. • Presystolic pulsation, synchronous with an audible fourth Presystolic pulsation, synchronous with an audible fourth

heart sound, reflecting a vigorous left atrial contraction heart sound, reflecting a vigorous left atrial contraction filling a ventricle with reduced compliance. filling a ventricle with reduced compliance.

• In the presence of left ventricular systolic dysfunction, an In the presence of left ventricular systolic dysfunction, an outward movement of the left ventricle can be palpated in outward movement of the left ventricle can be palpated in early diastole, coincident with a third heart sound.early diastole, coincident with a third heart sound.

HEART SOUNDS HEART SOUNDS • Ventricular dysfunction and/or prolongation of the P-R Ventricular dysfunction and/or prolongation of the P-R

interval makes soft first heart soundinterval makes soft first heart sound• Patients with marked ventricular dysfunction and/or left Patients with marked ventricular dysfunction and/or left

bundle branch block may have paradoxical splitting of the bundle branch block may have paradoxical splitting of the second heart sound.second heart sound.

• A fourth heart sound is almost universally present in A fourth heart sound is almost universally present in patients in sinus rhythm.patients in sinus rhythm.

• A third heart sound may be caused not only by left A third heart sound may be caused not only by left ventricular failure but also by increased inflow into the left ventricular failure but also by increased inflow into the left ventricle, as occurs when mitral regurgitation or ventricular ventricle, as occurs when mitral regurgitation or ventricular septal defect complicates STEMI. septal defect complicates STEMI.

MURMURS MURMURS • Mitral valve apparatus (papillary muscle dysfunction, left Mitral valve apparatus (papillary muscle dysfunction, left

ventricular dilation). ventricular dilation). • The systolic murmur of tricuspid regurgitation (caused by The systolic murmur of tricuspid regurgitation (caused by

right ventricular failure because of pulmonary hypertension right ventricular failure because of pulmonary hypertension and/or right ventricular infarction or by infarction of a right and/or right ventricular infarction or by infarction of a right ventricular papillary muscle) is also heard along the left ventricular papillary muscle) is also heard along the left sternal border. sternal border.

ABDOMEN. ABDOMEN. • Particularly in an inferior location with diaphragmatic irritation, Particularly in an inferior location with diaphragmatic irritation,

the pain may be localized to the epigastrium or the right upper the pain may be localized to the epigastrium or the right upper quadrant. quadrant.

• Right heart failure, characterized by hepatomegaly and a Right heart failure, characterized by hepatomegaly and a positive abdominojugular reflux. positive abdominojugular reflux.

EXTREMITIES. EXTREMITIES. • STEMI may have a history of intermittent claudication and STEMI may have a history of intermittent claudication and

demonstrate physical findings of PVD.demonstrate physical findings of PVD. NEUROPSYCHIATRIC FINDINGS. NEUROPSYCHIATRIC FINDINGS.

• Except for the altered mental status that occurs in patients with Except for the altered mental status that occurs in patients with STEMI who have a markedly reduced cardiac output and STEMI who have a markedly reduced cardiac output and cerebral hypoperfusion, the findings on neurological cerebral hypoperfusion, the findings on neurological examination are normal unless the patient has suffered cerebral examination are normal unless the patient has suffered cerebral embolism secondary to a mural thrombus. embolism secondary to a mural thrombus.

Laboratory Findings Laboratory Findings

Serum Markers of Cardiac Damage Serum Markers of Cardiac Damage • ST-segment elevation and Q waves are seen in only about ST-segment elevation and Q waves are seen in only about

half of MI cases on presentation. half of MI cases on presentation. • Enzyme diffuse into the cardiac interstitium and ultimately Enzyme diffuse into the cardiac interstitium and ultimately

into the microvasculature and lymphatics in the region of into the microvasculature and lymphatics in the region of the infarct The rate of appearance of these macromolecules the infarct The rate of appearance of these macromolecules in the peripheral circulation depends on several factors in the peripheral circulation depends on several factors including intracellular location, molecular weight, local including intracellular location, molecular weight, local blood and lymphatic flow, and the rate of elimination from blood and lymphatic flow, and the rate of elimination from the blood. the blood.

CREATINE KINASE ISOENZYMES. CREATINE KINASE ISOENZYMES. Three isoenzymes of CK exist (MM, BB, and MB). Three isoenzymes of CK exist (MM, BB, and MB). BB: Extracts of brain and kidney BB: Extracts of brain and kidney MB: Skeletal muscle (1 to 3%)(Mostly MM) The MB MB: Skeletal muscle (1 to 3%)(Mostly MM) The MB

isoenzymes of CK can also be present in minor quantities in isoenzymes of CK can also be present in minor quantities in the small intestine, tongue, diaphragm, uterus, and prostate. the small intestine, tongue, diaphragm, uterus, and prostate.

MM and MB: Heart MM and MB: Heart CK-MB mass/ CK activity (Relative index) of about 2.5 is CK-MB mass/ CK activity (Relative index) of about 2.5 is

indicative of a myocardial rather than a skeletal source of the indicative of a myocardial rather than a skeletal source of the CK-MB elevation. CK-MB elevation.

MYOGLOBIN. MYOGLOBIN. This monomeric heme protein is released into the circulation This monomeric heme protein is released into the circulation

from injured myocardial cells and can be detected within a few from injured myocardial cells and can be detected within a few hours after the onset of infarction. hours after the onset of infarction.

Peak levels of serum myoglobin are reached considerably Peak levels of serum myoglobin are reached considerably earlier (1 to 4 hours) than peak values of serum CK. earlier (1 to 4 hours) than peak values of serum CK.

TroponinTroponin

CARDIAC-SPECIFIC TROPONINS. CARDIAC-SPECIFIC TROPONINS. The troponin complex consists of three subunits that regulate The troponin complex consists of three subunits that regulate

the calcium-mediated contractile process of striated muscle. the calcium-mediated contractile process of striated muscle. • Troponin C, which binds Ca2+;Troponin C, which binds Ca2+;• Troponin I (TnI), which binds to actin and inhibits actin-Troponin I (TnI), which binds to actin and inhibits actin-

myosin interactions; and myosin interactions; and • Troponin T (TnT), which binds to tropomyosin, thereby Troponin T (TnT), which binds to tropomyosin, thereby

attaching the troponin complex to the thin filament. attaching the troponin complex to the thin filament.

Approximately 6% of Tnt and 2 to 3% of TnI is found in a Approximately 6% of Tnt and 2 to 3% of TnI is found in a cytosolic pool. cytosolic pool.

Although both TnT and TnI are present in cardiac and skeletal Although both TnT and TnI are present in cardiac and skeletal muscle, they are encoded by different genes and their amino muscle, they are encoded by different genes and their amino acid sequence differs. acid sequence differs.

cTnT assays are produced by a single manufacturer, leading to cTnT assays are produced by a single manufacturer, leading to relative uniformity of cutoffs, whereas several manufacturers relative uniformity of cutoffs, whereas several manufacturers produce cTnI assays. produce cTnI assays.

When cardiac troponins are released from myocytes, there is a When cardiac troponins are released from myocytes, there is a mixture of free cTnT and free cTnI along with a complex of mixture of free cTnT and free cTnI along with a complex of the I-C-T components that is further degraded to a complex of the I-C-T components that is further degraded to a complex of I-C and free cTnTI-C and free cTnT

SERUM LIPIDS SERUM LIPIDS For patients admitted beyond 24 to 48 hours, more accurate For patients admitted beyond 24 to 48 hours, more accurate

determinations of serum lipid levels are obtained about 8 determinations of serum lipid levels are obtained about 8 weeks after the infarction has occurred.weeks after the infarction has occurred.

HEMATOLOGICAL FINDINGS. HEMATOLOGICAL FINDINGS. High WBC develops within 2 hours, reaches a peak 2 to 4 High WBC develops within 2 hours, reaches a peak 2 to 4

days after infarction, and returns to normal in 1 week; days after infarction, and returns to normal in 1 week; ESR: is usually normal during the first day or two after ESR: is usually normal during the first day or two after

infarction, even though fever and leukocytosis may be present. infarction, even though fever and leukocytosis may be present. An elevated CRP level appears to identify patients with worse An elevated CRP level appears to identify patients with worse

angiographic appearance of the infarct artery and a greater angiographic appearance of the infarct artery and a greater likelihood of developing heart failure. likelihood of developing heart failure.

J-shaped relationship between baseline hemoglobin values and J-shaped relationship between baseline hemoglobin values and clinical events. 14 to 15gm/dl – 17gm/dlclinical events. 14 to 15gm/dl – 17gm/dl

EKGEKG Patients with an abnormal R wave in V1 (0.04 second in duration Patients with an abnormal R wave in V1 (0.04 second in duration

and/or R/S ratio ≥1 in the absence of pre-excitation or right and/or R/S ratio ≥1 in the absence of pre-excitation or right ventricular hypertrophy) with inferior or lateral Q waves have an ventricular hypertrophy) with inferior or lateral Q waves have an increased incidence of isolated occlusion of a dominant LAD increased incidence of isolated occlusion of a dominant LAD without collateral circulation; such patients have a lower ejection without collateral circulation; such patients have a lower ejection fraction, increased end-systolic volume, and higher complication fraction, increased end-systolic volume, and higher complication rate than patients with inferior infarction because of isolated rate than patients with inferior infarction because of isolated occlusion of the right coronary artery.occlusion of the right coronary artery.

Q-WAVE AND NON-Q-WAVE INFARCTION. Q-WAVE AND NON-Q-WAVE INFARCTION. ISCHEMIA AT A DISTANCE. ISCHEMIA AT A DISTANCE. Although precordial ST-segment depression associates more Although precordial ST-segment depression associates more

commonly with extensive infarction of the lateral, or inferior septal commonly with extensive infarction of the lateral, or inferior septal segments, rather than anterior wall subendocardial ischemia, segments, rather than anterior wall subendocardial ischemia, imaging techniques such as echocardiography are necessary to imaging techniques such as echocardiography are necessary to ascertain whether an anterior wall motion abnormality is present.ascertain whether an anterior wall motion abnormality is present.

EKGEKG

RIGHT VENTRICULAR INFARCTION. RIGHT VENTRICULAR INFARCTION. ST-segment elevation in right precordial leads (V1, V3R-ST-segment elevation in right precordial leads (V1, V3R-

V6R) is a relatively sensitive and specific sign of right V6R) is a relatively sensitive and specific sign of right ventricular infarction. ventricular infarction.

A QS or QR pattern in leads V3R and/or V4R also suggests A QS or QR pattern in leads V3R and/or V4R also suggests right ventricular myocardial necrosis but has less predictive right ventricular myocardial necrosis but has less predictive accuracy than ST-segment elevation in these leads.accuracy than ST-segment elevation in these leads.

Imaging Imaging

X-ray X-ray Up to 12 hours can elapse before pulmonary edema Up to 12 hours can elapse before pulmonary edema

accumulates after ventricular filling pressure has become accumulates after ventricular filling pressure has become elevated. elevated.

The post-therapeutic phase lag represents a longer time The post-therapeutic phase lag represents a longer time interval; up to 2 days are required for pulmonary edema to interval; up to 2 days are required for pulmonary edema to resorb and the radiographic signs of pulmonary congestion to resorb and the radiographic signs of pulmonary congestion to clear .clear .

ECHOCARDIOGRAPHY ECHOCARDIOGRAPHY • Wall motion abnormalityWall motion abnormality• Aortic dissection. Aortic dissection. • Severity of mitral or tricuspid regurgitation Severity of mitral or tricuspid regurgitation • Identification of the site of acute ventricular septal rupture, Identification of the site of acute ventricular septal rupture,

quantification of shunt flow across the resulting defect, and quantification of shunt flow across the resulting defect, and assessment of acute cardiac tamponade are also possible.assessment of acute cardiac tamponade are also possible.

COMPUTED TOMOGRAPHY COMPUTED TOMOGRAPHY

• It probably is more sensitive for thrombus detection than is It probably is more sensitive for thrombus detection than is echocardiography.echocardiography.

NUCLEAR IMAGING NUCLEAR IMAGING

• Cardiac radionuclide imaging for the diagnosis of MI Cardiac radionuclide imaging for the diagnosis of MI should be restricted to special limited situations in which should be restricted to special limited situations in which the triad of clinical history, ECG findings, and serum the triad of clinical history, ECG findings, and serum marker measurements is unavailable or unreliable.marker measurements is unavailable or unreliable.

ESTIMATION OF INFARCT SIZEESTIMATION OF INFARCT SIZE

ELECTROCARDIOGRAPHY. ELECTROCARDIOGRAPHY. • A relationship between the number of ECG leads showing A relationship between the number of ECG leads showing

ST-segment elevation and mortality rate exists.ST-segment elevation and mortality rate exists. SERUM CARDIAC MARKERS.SERUM CARDIAC MARKERS.

• Clinically, the peak CK or CK-MB provides an Clinically, the peak CK or CK-MB provides an approximate estimate of infarct size and is widely used approximate estimate of infarct size and is widely used prognostically.prognostically.

• Measuring a cardiac-specific troponin level several days Measuring a cardiac-specific troponin level several days after STEMI, even in cases of successful reperfusion, may after STEMI, even in cases of successful reperfusion, may provide a reliable estimate of infarct size because such late provide a reliable estimate of infarct size because such late troponin measurements reflect delayed release from the troponin measurements reflect delayed release from the myofilament bound pool in damaged myocytes.myofilament bound pool in damaged myocytes.

Thank you Thank you