Chapter 12: Ischemic Heart Disease Flashcards

Question

Clinically significant stenosing plaques may be located anywhere within these vessels **but tend to predominate** where?

Answer 1

Clinically significant stenosing plaques may be located anywhere within these vessels but tend to **predominate within the first several centimeters** of the **LAD and LCX** and **along the entire length of the RCA.**

Answer 2

Sometimes the major secondary epicardial branches are also involved * **d**iagonal branches of the LA**D**, * **obtuse** marginal branches of the **LCX**, or * posterior descending branch of the RCA)

Answer 3

True **but atherosclerosis of the intramural (penetrating) branches is *rare.***

Answer 4

* number, * distribution * structure, and * degree of obstruction of atheromatous plaques.

Answer 5

This is particularly true for the so-called **acute coronary syndromes**, **unstable angina**, **acute MI,** and **sudden death.**

Answer 6

The acute coronary syndromes are **typically initiated by an unpredictable** and **abrupt conversion of a stable atherosclerotic plaque** **to an unstable and potentially lifethreatening atherothrombotic lesion through rupture, superficial erosion, ulceration, fissuring, or deep hemorrhage**( Chapter 11 ).

Answer 7

In most instances, the **plaque change** causes the **formation of a superimposed thrombus** that **partially or completely occludes the affected artery**. [46] [47] These acute events are often associated with intralesional inflammation, which you will remember mediates the initiation, progression, and acute complications of atherosclerosis (discussed in Chapter 11 ) . For purposes of simplicity, the spectrum of acute alterations in atherosclerotic lesions will be termed either **plaque disruption or plaque change.**

Answer 8

* Stable angina * Unstable angina * MI * sudden cardiac death

Answer 9

Stable angina **results from increases in myocardial oxygen demand** that **outstrip the ability of stenosed** **coronary arteries to increase oxygen delivery;** it is ***_usually not associated with plaque disruption._***

Answer 10

Unstable angina is **caused by *_plaque rupture_* complicated by partially occlusive thrombosis** and **vasoconstriction, which lead to severe but transient reductions in coronary blood flow. In some cases, microinfarcts can occur distal to disrupted plaques due to thromboemboli.**

Answer 11

In MI, acute plaque change induces ***_total thrombotic occlusion and the subsequent death of heart muscle._***

Answer 12

Finally, sudden cardiac death **frequently involves an atherosclerotic lesio**n in which a **disrupted** **plaque causes regional myocardial ischemia** that **induces a fatal ventricular arrhythmia**. Each of these important syndromes is discussed in detail below, followed by an examination of the important myocardial consequences.

Answer 13

Angina pectoris **(literally, chest pain)**

Answer 14

FIGURE 12-9 Schematic of sequential progression of coronary artery lesions and their association with various acute coronary syndromes.

Answer 15

is **characterized by paroxysmal (sudden recurrence)** and **usually recurrent attacks of substernal**or**precordial chest**discomfort (variously described as**constricting, squeezing, choking, or knifelike)**caused by**transient (15 seconds to 15 minutes)** myocardial ischemia that **falls short of inducing myocyte necrosis**

Answer 16

The three overlapping patterns of angina pectoris— * (1) **stable or typical angina,** * (2) **Prinzmetal variant angina,** and * (3) **unstable or crescendo angina**— are **caused by varying combinations** of **increased myocardial demand,** **decreased myocardial perfusion**, and **coronary arterial pathology**.

Answer 17

FALSE Moreover, not all ischemic events are perceived by patients (silent ischemia).

Answer 18

Stable angina, the **most common form**, is also called **typical angina pectoris**. It is caused by an **imbalance in coronary perfusio**n (due to **chronic stenosing coronary atherosclerosis**) relative to myocardial demand, such as that **produced by physical activity, emotional excitement, or any other cause of increased cardiac workload**. ***Typical angina pectoris is usually relieved by rest (which decreases demand) or administering nitroglycerin, a strong vasodilator (which increases perfusion)***

Answer 19

True Typical angina pectoris is usually relieved by rest (which decreases demand) or administering nitroglycerin, a strong vasodilator (which increases perfusion)

Answer 20

Prinzmetal variant angina is an **uncommon from of episodic myocardial ischemia** that is **caused by coronary artery spasm**. Although individuals with Prinzmetal variant angina may well have significant coronary atherosclerosis, the **anginal attacks are unrelated to physical activity**, **heart rate, or blood pressur**e. Prinzmetal angina generally responds promptly to vasodilators, such as **nitroglycerin and calcium channel blockers**.

Answer 21

True Although individuals with Prinzmetal variant angina may well have significant coronary atherosclerosis, the anginal attacks are unrelated to physical activity, heart rate, or blood pressure. Prinzmetal angina generally responds promptly to vasodilators, such as nitroglycerin and calcium channel blockers.

Answer 22

Prinzmetal angina generally responds promptly to vasodilators, such as **nitroglycerin and calcium channel blockers.**

Answer 23

Unstable or crescendo angina **refers to a pattern of increasingly frequent pain**, **often of prolonged duration,**that is**precipitated by progressively lower levels of physical activity** or that **even occurs at rest**.

Answer 24

In most patients, unstable angina is caused by the **disruption of an atherosclerotic plaque**with**superimposed partial (mural) thrombosis**and**possibly embolization or vasospasm (or both).** **Unstable angina** thus serves as a warning that an acute MI may be imminent; indeed, this syndrome is sometimes referred to as **preinfarction angina**

Answer 25

Unstable angina thus serves as a warning that an acute MI may be imminent; indeed, this syndrome is sometimes referred to as **preinfarction angina**

Answer 26

MI**, also known as “heart attack**,” is the **death of cardiac muscle due to prolonged severe ischemia**. **It is by far the most important form of IHD**. About 1.5 million individuals in the United States suffer an MI annually.

Answer 27

MI can occur at **virtually any age**, but its frequency rises **progressively with increasing age** and when **predispositions to atherosclerosis are present**

Answer 28

Nearly **10%** of myocardial infarcts occur in **people under age 40**,

Answer 29

and 45% occur in people under age 65.

Answer 30

FALSE Blacks and whites are equally affected.

Answer 31

FALSE Throughout life, **men are at significantly greater risk than women.** Indeed, except * *for those having some predisposing atherogenic condition**, **women are protected against MI** and * *other heart diseases** during the **reproductive years.** However, the **decrease of estrogen** **following menopause** is associated with rapid **development of CAD**, and **IHD is the most common cause of death in elderly women.** Postmenopausal hormonal replacement therapy is not currently felt to protect against atherosclerosis and IHD ( Chapter 11 ).

Answer 32

Indeed, except for those having some predisposing atherogenic condition, **women are protected against MI** and **other heart diseases during the reproductive years.** However, the **decrease of estrogen following menopause is associated with rapid development of CAD**, and**IHD is the most common cause of death in elderly women.** Postmenopausal hormonal replacement therapy is not currently felt to protect against atherosclerosis and IHD ( Chapter 11 ).

Answer 33

* Coronary Arterial Occlusion * Myocardial Response. * Transmural Versus Subendocardial Infarction * Infarct Modification by Reperfusion.

Answer 34

* **sudden change in atheromatous plaque** * **platelet activation due to endotheilal exposure to collagen** * **Vasospasm from mediators released by platelets** * **Coagulation pathway activated** * **Frequently within minutes, the thrombus evolves to completely occlude the lumen of the vessel. **

Answer 35

The initial event is a **sudden change in an atheromatous** **plaque,** which may consist of i**ntraplaque hemorrhage, erosion or ulceration, or rupture or fissuring.**

Answer 36

* intraplaque hemorrhage, * erosion or ulceration, or * rupture or fissuring.

Answer 37

* **,platelets** **adhere,** * become **activated**, * **release** their granule contents, * and **aggregate to form microthrombi.**

Answer 38

Vasospasm is stimulated by mediators released from platelets.

Answer 39

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

Answer 40

**Frequently within minutes**, the thrombus evolves to completely occlude the lumen of the vessel.

Answer 41

Compelling evidence for this sequence has been obtained from * (1) **autopsy** studies of patients dying of acute MI, * (2**) angiographic studies** demonstrating a high frequency of thrombotic occlusion early after MI * (3) the **high success rate of coronary revascularization** (i.e., thrombolysis, angioplasty, stent placement, and surgery) following MI, and * (4) the **demonstration of residual disrupted atherosclerotic lesions** by angiography after thrombolysis.

Answer 42

Coronary angiography performed **within 4 hours** of the onset of an MI shows a **thrombosed** **coronary artery** in almost 90% of cases.

Answer 43

However, when **angiography is delayed until 12 to 24** hours **after onset, occlusion is seen only about 60%** of the time, **suggesting that some occlusions resolve due to fibrinolysis, relaxation of spasm, or both.**

Answer 44

* **Vasospasm with or without coronary atherosclerosis** * **Emboli** * **Ischemia**

Answer 45

Vasospasm with or without coronary atherosclerosis, perhaps in association with platelet aggregation or due to **cocaine abuse**

Answer 46

* Emboli from the left atrium in **association with atrial fibrillation**, a **left-sided mural thrombus, vegetations of infective endocarditis,** **intracardiac prosthetic material;** or * paradoxical emboli from the right side of the heart or the peripheral veins, which travel through a patent foramen ovale to the coronary arteries

Answer 47

by disorders of small intramural coronary vessels, such as: * **vasculitis,** * **hematologic abnormalities such as sickle cell disease,** * **amyloid deposition in vascular walls, and** * **vascular dissection;** * **lowered systemic blood pressure (shock); or** * **inadequate myocardial “protection” during cardiac surgery**

Answer 48

Coronary arterial obstruction compromises the blood supply to a region of myocardium ( Fig. 12-10 ), causing ischemia, myocardial dysfunction, and potentially myocyte death. The **anatomic region supplied by that artery** is referred to as the area at risk . The outcome depends predominantly on the severity and duration of flow deprivation ( Fig. 12-11 ).

Answer 49

FIGURE 12-10 Postmortem angiogram showing the **posterior aspect of the heart** of a patient who **died during the evolution of acute myocardial infarction**, ***demonstrating total occlusion of the distal right coronary artery***by an**acute thrombus (**arrow) and a**large zone of myocardial hypoperfusion** involving the posterior left and right ventricles, as indicated by arrowheads, and having almost absent filling of capillaries. The heart has been fixed by coronary arterial perfusion with glutaraldehyde and cleared with methyl salicylate, followed by intracoronary injection of silicone polymer (yellow). Photograph courtesy of Lewis L. Lainey.

Answer 50

FIGURE 12-11 Temporal sequence of early biochemical findings and progression of necrosis after onset of severe myocardial ischemia. * A, Early changes include **loss of adenosine triphosphate (ATP)** and **accumulation of lactate** * B, For **approximately 30 minutes** after the onset of even the **most severe ischemia, myocardial injury is potentially reversible.** Thereafter, **progressive loss of viability occurs that is complete by 6 to 12 hours**. The benefits of reperfusion are greatest when it is achieved early, and are progressively lost when reperfusion is delayed.

Answer 51

* A, **Early changes include loss of** **adenosine triphosphate (ATP)** and **accumulation of lactate.** * B, For **approximately 30 minutes** after the onset of even the most severe ischemia, myocardial injury is potentially reversible. Thereafter, progressive loss of viability occurs that is complete by 6 to 12 hours. The benefits of reperfusion are greatest when it is achieved early, and are progressively lost when reperfusion is delayed.

Answer 52

The early biochemical consequence of myocardial ischemia is the **cessation of aerobic metabolism within seconds**, leading to**inadequate production of high-energy phosphates** (e.g., creatine phosphate and adenosine triphosphate) and **accumulation of potentially noxious metabolites** (such as lactic acid) ( Fig. 12-11A ).

Answer 53

60 seconds. This cessation of function **can precipitate acute heart failure long before myocardial cell death.** As detailed in Chapter 1 , **ultrastructural changes (including myofibrillar relaxation, glycogen** **depletion, cell and mitochondrial swelling)** also develop within a few minutes of the onset of ischemia. Nevertheless, these early changes are potentially reversible.

Answer 54

10% or less of normal).

Answer 55

A key feature that marks the early phases of myocyte necrosis is the **disruption of the integrity of the sarcolemmal membrane**, which allows**intracellular macromolecules to leak out of cells into the cardiac interstitium**and**ultimately into the microvasculature and lymphatics** in the region of the infarct.

Answer 56

Feature :Time * Onset of ATP depletion: Seconds * Loss of contractility :\<2 min * ATP reduced * to 50% of normal : 10 min * to 10% of normal: 40 min * Irreversible cell injury: 20–40 min * Microvascular injury : \>1 hr

Answer 57

(usually at least 2 to 4 hours), ( Fig. 12-11B ). This delay in the onset of permanent myocardial injury provides the rationale for rapid diagnosis in acute MI—to permit early coronary intervention, the purpose of which is to establish reperfusion and salvage as much “at risk” myocardium as possible

Answer 58

subendocardium

Answer 59

in the **subendocardial zone**.

Answer 60

* The **location**, **severity, and rate** of development of coronary obstructions due to atherosclerosis and thromboses * • The **size of the vascular bed** **perfused** by the obstructed vessels * • The **duration of the occlusion** * • The **metabolic/oxygen needs** of the myocardium at risk * • The **extent of collateral blood vessels** * • The **presence, site, and severity** of coronary arterial spasm * • Other factors, such as **heart rate, cardiac rhythm, and blood oxygenation**

Answer 61

FIGURE 12-12 Progression of myocardial necrosis after coronary artery occlusion. * Necrosis begins in a small zone of the myocardium beneath the endocardial surface in the center of the ischemic zone. * The area that depends on the occluded vessel for perfusion is the “at risk” myocardium (shaded). * Note that a very narrow zone of myocardium immediately beneath the endocardium is spared from necrosis because it can be oxygenated by diffusion from the ventricle.

Answer 62

Necrosis is usually complete within 6 hours of the onset of severe myocardial ischemia. However, in **instances where the coronary arterial collateral system**, **stimulated by chronic ischemia,** is better developed and thereby more effective, the progression of necrosis may follow a more protracted **course (possibly over 12 hours or longer)**

Answer 63

* apex of the heart (distal end of the ventricles), * the anterior wall of the left ventricle, and the anterior two thirds of the ventricular septum.

Answer 64

By convention, th**e coronary artery** ***(either the right coronary artery [RCA] or the left circumflex artery [LCX])*** that perfuses the posterior third of the septum is called “dominant” (even though the **LAD and LCX collectively perfuse the majority of the left ventricular myocardium).**

Answer 65

In a **right dominant circulation**, present in approximately **four fifths of individuals,**the**LCX generally perfuses only the lateral wall of the left ventricle**, and the**RCA supplies the entire right ventricular free wall,**the**posterobasal wall of the left ventricle,** and the **posterior third of the ventricular septum.** Thus, occlusions of the RCA (as well as the left coronary artery) can **cause left ventricular damage.** The right and left coronary arteries function as end arteries, a**right and left coronary arteries function** **as end arteries,** although anatomically most hearts have numerous intercoronary anastomoses (connections called the collateral circulation). Little blood courses through the collateral circulation in the normal heart. However, when one artery is severely narrowed, blood flows via collaterals from the high- to the low-pressure system, and causes the channels to enlarge. Thus, progressive dilation and growth of collaterals, stimulated by ischemia, may play a role in providing blood flow to areas of the myocardium otherwise deprived of adequate perfusion.

Answer 66

the **location and cause of the decreased** **perfusion** ( Fig. 12-16 ).

Answer 67

Most myocardial infarcts are **transmural**, in which the ischemic necrosis involves the full or nearly full thickness of the ventricular wall in the distribution of a single coronary artery. This pattern of infarction is usually associated with a combination of chronic coronary atherosclerosis, acute plaque change, and superimposed thrombosis (as discussed previously).

Answer 68

Most myocardial infarcts are **transmural**, in which the **ischemic necrosis involves the full or nearly full thickness of the ventricular wall** in the **distribution of a single coronary artery.** Most myocardial infarcts are transmural, in which the ischemic necrosis involves the full or nearly full thickness of the ventricular wall in the distribution of a single coronary artery. This pattern of infarction is usually associated with a combination of chronic coronary atherosclerosis, acute plaque change, and superimposed thrombosis (as discussed previously).

Answer 69

* chronic coronary atherosclerosis, * acute plaque change, * and superimposed thrombosis (as discussed previously).

Answer 70

In contrast, a subendocardial (nontransmural) infarct **constitutes an area of** **ischemic necrosis** limited to the **inner one third to one half of the ventricular wall.** As the subendocardial zone is **normally the least perfused** region of myocardium, **this area is most** **vulnerable to any reduction in coronary flow**.

Answer 71

**plaque disruption** followed by a **coronary thrombus that becomes lysed before myocardial necrosis extends across the full thickness of the wall**; in this case the**infarct will be limited to the distribution of the coronary artery that suffered plaque change.** However, subendocardial infarcts **can also result from prolonged, severe reduction in systemic blood pressure**, as in **shock superimposed on chronic,** otherwise **noncritical, coronary stenoses.** In the subendocardial infarcts that occur as a result of global hypotension, myocardial damage is usually circumferential, rather than being limited to the distribution of a single major coronary artery. Owing to the characteristic electrocardiographic changes resulting from myocardial ischemia/necrosis in various distributions, transmural infarcts are often referred to as “ST elevation infarcts” and subendocardial infarcts are known as “non-ST elevation infarcts.”

Answer 72

* *circumferential**, **rather than being limited to the distribution of a single major coronary artery. **

Answer 73

“ST elevation infarcts”

Answer 74

“non-ST elevation infarcts.”

Answer 75

FIGURE 12-16 Consequences of myocardial ischemia followed by reperfusion. * A, Schematic illustration of the progression of myocardial ischemic injury and its modification by restoration of flow (reperfusion). Hearts suffering brief periods of ischemia of longer than 20 minutes followed by reperfusion do not develop necrosis (reversible injury). Brief ischemia followed by reperfusion results in stunning. If coronary occlusion is extended beyond 20 minutes' duration, a wavefront of necrosis progresses from subendocardium to subepicardium over time. Reperfusion before 3 to 6 hours of ischemia salvages ischemic but viable tissue. This salvaged tissue may also demonstrate stunning. Reperfusion beyond 6 hours does not appreciably reduce myocardial infarct size. * B, Gross and * C, microscopic appearance of myocardium modified by reperfusion. * B, Large, densely hemorrhagic, anterior wall acute myocardial infarction in a patient with left anterior descending artery thrombus treated with streptokinase, a fibrinolytic agent (triphenyl tetrazolium chloride–stained heart slice). Specimen oriented with posterior wall at top. * C, Myocardial necrosis with hemorrhage and contraction bands, visible as dark bands spanning some myofibers (arrow). This is the characteristic appearance of markedly ischemic myocardium that has been reperfused.

Answer 76

Time: **0–½ hr** Gross Features:**None** Light Microscope **:None** Electron Microscope: **Ralaxation of myofibrils; glycogen loss; mitochondrial swelling**

Answer 77

* Time : **½–4 hr** * Gross Features : **None** * Light Microscope: **Usually none; variable waviness of fibers at border** * Electron Microscope: **Sarcolemmal disruption**

Answer 78

Time **: 4–12 hr** Gross Features : **Dark mottling (occasional)** Light Microscope: **Early coagulation necrosis; edema; hemorrhage** Electron Microscope: **Sarcolemmal disruption; mitochodrial amorphous densities**

Answer 79

Time :**12–24 hr** Gross Features : **Dark mottling** Light Microscope: **Ongoing coagulation necrosis; pyknosis of nuclei; myocyte hypereosinophilia; marginal contraction band necrosis; early neutrophilic infiltrate** Electron Microscope: **Sarcolemmal disruption; mitochodrial amorphous densities**

Answer 80

Time : **1–3 days** Gross Features : **Mottling with yellowtan infarct center** Light Microscope:**Coagulation necrosis, with loss of nuclei and striations; brisk interstitial infiltrate of neutrophils** Electron Microscope: **Sarcolemmal disruption; mitochodrial amorphous densities**

Answer 81

Time : **3–7days** Gross Features : **Hyperemic border; central yellow-tan softening** Light Microscope:**Beginning disintegration of dead myofibers,with dying neutrophils; early phagocytosis of dead cells by macrophages at infarct border** Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Answer 82

Time : **7–10 days** Gross Features :**Maximally yellow-tan and soft, with depressed red-tan margins** Light Microscope:**Well-developed phagocytosis of dead cells; early formation of fibrovascular granulation tissue at margins** Electron Microscope: **Sarcolemmal disruption; mitochodrial amorphous densities**

Answer 83

Time : **10 –14 days** Gross Features :**Red-gray depressed infarct borders**and soft, with depressed red-tan margins Light Microscope:**Well-established granulation tissue with new blood vessels and collagen deposition** Electron Microscope: **Sarcolemmal disruption; mitochodrial amorphous densities**

Answer 84

Time :**2–8 wk** Gross Features :**Gray-white scar, progressive from border toward core of infarct** Light Microscope:**Increased collagen deposition, with decreased cellularity** Electron Microscope: **Sarcolemmal disruption; mitochodrial amorphous densities**

Answer 85

Time :**\>2 mo** Gross Features :**Scarring complete** Light Microscope:**Dense collagenous scar** Electron Microscope: **Sarcolemmal disruption; mitochodrial amorphous densities**

Answer 86

FIGURE 12-13 Distribution of myocardial ischemic necrosis correlated with the location and nature of decreased perfusion. Left, The positions of transmural acute infarcts resulting from occlusions of the major coronary arteries; top to bottom, left anterior descending, left circumflex, and right coronary arteries. Right, The types of infarcts that result from a partial or transient occlusion, global hypotension, or intramural small vessel occlusions

Answer 87

Nearly **all transmural infarcts** involve **at least a portion of the left ventricle (comprising the free wall and ventricular septum)** and **encompass nearly the entire perfusion zone of the occluded coronary artery save for a narrow rim (∼0.1 mm)** of preserved subendocardial myocardium that is sustained by the diffusion of oxygen and nutrients from the ventricular lumen.

Answer 88

* **Left anterior descending coronary artery** (40% to 50%): infarcts involving the anterior wall of left ventricle near the apex; the anterior portion of ventricular septum; and the apex circumferentially * • **Right coronary artery (30% to 40%)**: infarcts involving the inferior/posterior wall of left ventricle; posterior portion of ventricular septum; and the inferior/posterior right ventricular free wall in some cases * • **Left circumflex coronary artery (15% to 20%):** infarcts involving the lateral wall of left ventricle except at the apex

Answer 89

**Left anterior descending coronary artery** (40% to 50%)

Answer 90

infarcts involving the: * **anterior** **wall of left ventricle near the apex**; * the **anterior portion of ventrcular septum**; and the * **apex circumferentially**

Answer 91

* infarcts involving the ***inferior/posterior* wall of left ventricle;** * ***posterior portion* of ventricular septum**; and the * ***inferior/posterior* right ventricular free wall in some cases**

Answer 92

infarcts involving the lateral wall of left ventricle **except at the apex**

Answer 93

* **left main coronary artery**, * the **secondary branches of the left** * **anterior descending coronary artery**, or the * **marginal branches of the left circumflex coronary artery.**

Answer 94

are usually not apparent on gross examination.

Answer 95

* *immersion of tissue slices in a solution of** * *triphenyltetrazolium chloride**. This histochemical stain imparts a brick-red color to intact, noninfarcted myocardium where **dehydrogenase (e.g., lactate dehydrogenase) activity** is preserved. **Because dehydrogenases leak out through the damaged membranes of dead cell**, an **infarct appears as an unstained pale zone** ( Fig. 12-14 ). By 12 to 24 **hours an infarct can** **be identified grossly in transverse slices as a reddish-blue area of discoloration caused by stagnated, trapped blood.** Thereafter, the infarct becomes progressively more sharply defined, yellow-tan, and soft. By 10 days to 2 weeks, it is rimmed by a hyperemic zone of highly vascularized granulation tissue. Over the succeeding weeks, the injured region evolves to a fibrous scar.

Answer 96

**6 to 12 hours.** **“Wavy fibers”** may be present at the **periphery of the infarct;** these changes **probably result from the forceful systolic tugs** of the viable fibers on immediately adjacent, noncontractile dead fibers, which stretches and folds them An additional sublethal ischemic change may be seen in the margins of infarcts: so-called vacuolar degeneration or **myocytolysis**, which takes the form of large vacuolar spaces within cells that probably contain water. The necrotic muscle elicits acute inflammation (most **prominent between 1 and** **3 days).** Thereafter macrophages remove the necrotic myocytes (most pronounced at 3 to 7 days), and the damaged zone is progressively replaced by the ingrowth of highly vascularized granulation tissue (most prominent at 1 to 2 weeks); as healing progresses, this is replaced by fibrous tissue. In most instances, scarring is well advanced by the end of the sixth week, but the efficiency of repair depends on the size of the original lesion

Answer 97

An **additional sublethal ischemic change** may be seen in the **margins of infarcts:** so-called **vacuolar degeneration or myocytolysis**, which **takes the form of large vacuolar spaces within cells that probably** **contain water.**

Answer 98

Since healing requires the participation of inflammatory cells that **migrate to the region of damage through intact blood vessel**s, which often**survive only at the infarct margins,** the **infarct heals from its margins toward its center.** Thus, a large infarct may not heal as quickly or as completely as a small one. A **healing infarct may appear nonuniform**, with the **mostadvanced healing at the periphery.** Once a lesion is completely healed, it is impossible to determine its age (i.e., the dense fibrous scar of 8-week-old and 10-year-old infarcts may look identical).

Answer 99

Infarcts may expand beyond their original borders over a period of days to weeks via a process of repetitive necrosis of adjacent regions (extension). In such cases, there is a **central zone in which healing is more advanced than the periphery of the infarct.** This contrasts with the appearance of a simple infarct described above, in which the most advanced repair is peripheral. Infarct extension may occur because of retrograde propagation of a thrombus, proximal vasospasm, progressively impaired cardiac contractility that renders flow through moderate stenoses insufficient, the deposition of platelet-fibrin microemboli, or an arrhythmia that impairs cardiac function.

Answer 100

``` FIGURE 12-14 Acute myocardial infarct, predominantly of the posterolateral left ventricle, demonstrated histochemically by a lack of staining by triphenyltetrazolium chloride in areas of necrosis (arrow). ``` The staining defect is due to the enzyme leakage that follows cell death. Note the myocardial hemorrhage at one edge of the infarct that was associated with cardiac rupture, and the anterior scar (arrowhead), indicative of old infarct. Specimen is oriented with the posterior wall at the top. Ischemic Heart Disease 1023

Answer 101

FIGURE 12-15 Microscopic features of myocardial infarction and its repair. * A, One-day-old infarct showing coagulative necrosis and wavy fibers (elongated and narrow, as compared with adjacent normal fibers at right). Widened spaces between the dead fibers contain edema fluid and scattered neutrophils. * B, Dense polymorphonuclear leukocytic infiltrate in area of acute myocardial infarction of 3 to 4 days' duration. * C, Nearly complete removal of necrotic myocytes by phagocytosis (approximately 7 to 10 days). * D, Granulation tissuecharacterized by loose collagen and abundant capillaries. * E, Well-healed myocardial infarct with replacement of the necrotic fibers by dense collagenous scar. A few residual cardiac muscle cells are present.

Answer 102

Infarct Modification by Reperfusion.

Answer 103

The most effective way to “rescue” ischemic myocardium threatened by infarction is to **restore** **myocardial blood flow as rapidly as possible**, a process referred to as **reperfusion**.

Answer 104

The most effective way to “rescue” ischemic myocardium threatened by infarction **is to restore myocardial blood flow as rapidly as possible**, a process referred to as reperfusion.

Answer 105

True Although reperfusion can often be accomplished, reperfusion may also trigger deleterious complications, including **arrhythmias, myocardial hemorrhage with contraction bands**, **irreversible cell damage** **superimposed on the original ischemic injury (reperfusion injury), microvascular injury,** and **prolonged ischemic dysfunction (myocardial stunning)**

Answer 106

, irreversible cell damage superimposed on the original ischemic injury (reperfusion injury), microvascular injury, and

Answer 107

prolonged ischemic dysfunction (myocardial stunning)

Answer 108

**Coronary intervention (i.e., thrombolysis, angioplasty,** **stent placement, or coronary artery bypass graft [CABG] surgery)** is often used in an attempt to dissolve, mechanically alter, or bypass the lesion that initiated the acute MI. The purpose of these treatments is to **restore blood flow to the area at risk for infarction and rescue the ischemic**(but not yet necrotic) heart muscle.**Because loss of myocardial viability in infarction is progressive, occurring over a period of at least several hours early reperfusion can salvage myocardium and thereby limit infarct size, with consequent improvement in both short- and long-term function and survival.**

Answer 109

* (1) the **rapidity with which the coronary obstruction is alleviated (the** **first 3 to 4 hours following onset are critical)** and * (2) the **extent of correction of the vascular** **occlusion** and the u**nderlying causal lesion.**For example, thrombolysis can remove a thrombus occluding a coronary artery, but does not alter the underlying atherosclerotic plaque that initiated it. In contrast, percutaneous transluminal coronary angioplasty (PTCA) with stent placement not only eliminates a thrombotic occlusion but also can relieve some of the original obstruction and instability caused by the underlying disrupted plaque. CABG provides flow around a blocked vessel.

Answer 110

FIGURE 12-17 Effects of reperfusion on myocardial viability and function. Following coronary occlusion, contractile function is lost within 2 minutes and viability begins to diminish after approximately 20 minutes. If perfusion is not restored (A), then nearly all myocardium in the affected region will die. B, If flow is restored, then some necrosis is prevented, myocardium is salvaged, and at least some function will return. The earlier reperfusion occurs, the greater the degree of salvage. However, the process of reperfusion itself may induce some damage (reperfusion injury), and return of function of salvaged myocardium may be delayed for hours to days (post-ischemic ventricular dysfunction) .

Answer 111

TRUE As indicated in Figure 12-16A , reperfusion of myocardium within 20 minutes of the onset of ischemia may completely prevent necrosis. Reperfusion after a longer interval may not prevent all necrosis but can salvage at least some myocytes that would have otherwise died. ``` Recall that (1) severe ischemia does not cause immediate cell death even in the most severely affected regions of myocardium, and (2) not all regions of myocardium are equally ischemic. ```

Answer 112

A reperfused infarct i**s usually hemorrhagic** because the **vasculature is injured during the period** **of ischemia and leaks when flow is restored.**

Answer 113

Microscopic examination reveals that myocytes that were irreversibly injured at the time of reperfusion often contain **contraction bands**, intensely **eosinophilic intracellular “stripes”** composed of closely **packed sarcomeres**. These result from the **exaggerated contraction of myofibrils** when **perfusion is reestablished,** at which time the interior of dead cells with damaged plasma membranes are exposed to a high concentration of calcium ions from the plasma. Thus, reperfusion not only salvages reversibly injured cells but also alters the morphology of lethally injured cells.

Answer 114

True ``` In addition to its benefits, reperfusion may also have some deleterious effects on the vulnerable ischemic myocardium (reperfusion injury; see Fig. 12-17B ). [52] ``` The clinical significance of myocardial reperfusion injury is uncertain. As discussed in Chapter 1 , **reperfusion injury may be mediated by oxidative stress, calcium overload, and potentially inflammation initiated during reperfusion**. Reperfusion-induced microvascular injury causes not only hemorrhage but also endothelial swelling that occludes capillaries and may limit the reperfusion of critically injured myocardium **(called no-reflow).**

Answer 115

Reperfusion-induced microvascular injury causes not only hemorrhage but also endothelial swelling that occludes capillaries and may limit the reperfusion of critically injured myocardium

Answer 116

Biochemical abnormalities may also persist for a period of days to several weeks in myocytes that are rescued from ischemia by reperfusion. These are thought to underlie a phenomenon referred to as **stunned myocardium**, **a state of reversible cardiac failure that usually recovers** **after several days.** [53] Reperfusion also frequently induces arrhythmias.

Answer 117

Myocardium that is subjected to chronic, sublethal ischemia may also **enter into a state of lowered metabolism and** **function that is referred to as hibernation.** [54]

Answer 118

The function of hibernating myocardium may be restored by revascularization (e.g., by CABG surgery, angioplasty, or stenting).

Answer 119

Paradoxically, repetitive short-lived transient severe ischemia may protect the myocardium against infarction (a phenomenon known as **preconditioning**) by mechanisms that are not understood

Answer 120

MI is **diagnosed by clinical symptoms**, **laboratory tests** for the **presence of myocardial proteins in the plasma**, and**characteristic electrocardiographic changes.**

Answer 121

Patients with MI often present with **a rapid, weak pulse and profuse sweating** **(diaphoresis)**. **Dyspnea due to impaired contractility** of the ischemic myocardium and the resultant pulmonary congestion and edema is common. However, in about **10% to 15% of patients the onset is entirely asymptomatic** and the disease is discovered only by **electrocardiographic changes or laboratory tests that show evidence of myocardial damage (see below)**.

Answer 122

Such “silent” MIs are particularly common in elderly patients and in the setting of diabetes mellitus.

Answer 123

The laboratory evaluation of MI is based on **measuring the blood levels of proteins that leak out** **of fatally injured myocytes**; these molecules include **myoglobin, cardiac troponins T and I, the** **MB fraction of creatine kinase (CK-MB), lactate dehydrogenase, and many others** ( Fig. 12-18 ). [56]

Answer 124

The diagnosis of myocardial injury is established when blood levels of these cardiac biomarkers are increased in the clinical setting of acute ischemia. The rate of appearance of these markers in the peripheral circulation depends on several factors, including their **intracellular location and molecular weight, the blood flow and lymphatic drainage in the area of the infarct, and the rate of elimination of the marker from the blood.**

Answer 125

FIGURE 12-18 Release of myocyte proteins in myocardial infarction. Some of these proteins (e.g., troponin I, C, or T and creatine phosphokinase, MB fraction [CK-MB]) are used as diagnostic biomarkers.

Answer 126

The most sensitive and specific biomarkers of myocardial damage are : * cardiac-specific proteins, particularly **Troponins I and T (proteins that regulate calcium-mediated contraction of cardiac and skeletal muscle). Troponins I and T are not normally detectable in the circulation.** **Following an MI, levels of both begin to rise at 2 to 4 hours and peak at 48 hours.** Formerly the “gold standard,” cardiac creatine kinase remains useful.

Answer 127

2 to 4 hours

Answer 128

peak at 48 hours.

Answer 129

Creatine kinase, an enzyme that is **present in brain,** **myocardium**, and **skeletal muscle,** is a dimer composed of **two isoforms designated “M” and “B.”**

Answer 130

MM homodimers are found predominantly in cardiac and skeletal muscle

Answer 131

BB homodimers in brain, lung, and many other tissues;

Answer 132

**MB** heterodimers principally in cardiac muscle, with lesser amounts also being found in skeletal muscle. As a result, the MB form of creatine kinase (CK-MB) is **sensitive but not specific,** since i**t is also elevated when skeletal muscle is injured.** CK-MB begins to rise within 2 to 4 hours of the onset of MI, peaks at about 24 hours, and returns to normal within approximately 72 hours. Although the diagnostic sensitivities of cardiac troponin and CK-MB measurements are similar in the early stages of MI, elevated troponin levels persist for approximately 7 to 10 days after acute MI, well after CK-MB levels have returned to normal. Troponin and CK-MB levels peak earlier in patients whose hearts are successfully reperfused, because proteins are washed out of the necrotic tissue more rapidly. Unchanged levels of CK-MB and troponin over a period of 2 days essentially excludes the diagnosis of MI.

Answer 133

CK-MB begins to **rise within 2 to 4 hours** of the onset of MI, peaks at about 24 hours, and returns to normal within approximately 72 hours.

Answer 134

CK-MB begins to rise within 2 to 4 hours of the onset of MI, **peaks at about 24 hours**, and returns to normal within approximately 72 hours. Although the diagnostic sensitivities of cardiac troponin and CK-MB measurements are **similar in the early stages of MI,** elevated troponin levels persist for approximately 7 to 10 days after acute MI, well after CK-MB levels have returned to normal.

Answer 135

Troponin and CK-MB levels peak earlier in patients whose hearts are successfully reperfused, because **proteins are washed out of the necrotic tissue** **more rapidly.**

Answer 136

Unchanged levels of CK-MB and troponin over a period of 2 days essentially excludes the diagnosis of MI.

Answer 137

Therapies given routinely in the setting of acute MI include: * aspirin and heparin (to prevent further thrombosis); * oxygen (to minimize ischemia); * nitrates (to induce vasodilation and reverse vasospasm); * beta-adrenergic inhibitors (beta-blockers, to diminish cardiac oxygen demand and decrease the risk of arrythmias); * angiotensinogen converting enzyme (ACE) inhibitors (to limit venticular dilation); * and maneuvers that aim to open up blocked vessels, including the **administration of fibrinolytic agents, coronary angioplasty with o**r without stenting, and emergent CABG surgery. The choice of therapy depends on the clinical picture and the expertise of the treating institution. **Angioplasty** is highly effective in skilled hands, while **fibinolytic therapy can be given with almost equivalent efficacy by simple infusion.**

Answer 138

In general, factors associated with a poor prognosis include: * **advanced age,** * **female gender,** * **diabetes mellitus, and,** * **as a result of the cumulative loss of functional myocardium,** * **previous MI.**

Answer 139

* **Contractile dysfunction.** * **Arrhythmias.** * **Myocardial rupture** * **Pericarditis** * **Right ventricular infarction** * **Infarct extension** * **Infarct expansion** * **Mural thrombus** * **Ventricular aneurysm** * **Papillary muscle dysfunction** * **Progressive late heart failure (chronic IHD is discussed below).**

Answer 140

FIGURE 12-19 Complications of myocardial infarction. Cardiac rupture syndromes (A–C). ## Footnote A,Anterior myocardial rupture in an acute infarct (arrow). B, Rupture of the ventricular septum (arrow). C, Complete rupture of a necrotic papillary muscle. D, Fibrinous pericarditis, showing a dark, roughened epicardial surface overlying an acute infarct. E, Early expansion of anteroapical infarct with wall thinning (arrow) and mural thrombus. F, Large apical left ventricular aneurysm. The left ventricle is on the right in this apical four-chamber view of the heart.

Answer 141

Contractile dysfunction. Myocardial infarcts **produce abnormalities in left ventricular function roughly proportional to their size.** There is **usually some degree of left ventricular failure with hypotension, pulmonary vascular congestion, and interstitial pulmonary transudates,**which may**progress to frank pulmonary edema and respiratory impairment.** Severe “pump failure” (cardiogenic shock) occurs in 10% to 15% of patients following acute MI, generally those with a large infarct (\>40% of the left ventricle). Cardiogenic shock has a nearly 70% mortality rate and accounts for two thirds of inhospital deaths.

Answer 142

Arrhythmias. Many patients have **myocardial irritability and/or conduction disturbances** following MI that **lead to potentially fatal arrhythmias.**

Answer 143

* **sinus bradycardia,** * **heart block (asystole),** * **tachycardia,** * **ventricular premature contractions or ventricular tachycardia,** * **and ventricular fibrillation.** Because of the location of portions of the atrioventricular conduction system (bundle of His) in the inferoseptal myocardium, infarcts of this region may also be associated with heart block.

Answer 144

Myocardial rupture. The cardiac rupture syndromes result from softening and weakening of the necrotic and subsequently inflamed myocardium.

Answer 145

They include (1) **rupture of the ventricular free wall** (most common), with hemopericardium and cardiac tamponade ( Fig. 12-19A ); (2) **rupture of the ventricular septum** (less common), leading to an acute VSD and left-to-right shunting ( Fig. 12-19B ); and (3) **papillary muscle rupture (least common),** resulting in the acute onset of severe mitral regurgitation ( Fig. 12-19C ).

Answer 146

(1) r**upture of the ventricular free wal**l (most common), with hemopericardium and cardiac tamponade ( Fig. 12-19A );

Answer 147

to an acute VSD and left-to-right shunting

Answer 148

(3) **papillary muscle rupture (least common)**, resulting in the **acute onset of severe mitral regurgitation** ( Fig. 12-19C ).

Answer 149

Free-wall rupture is most frequent **3 to 7 days after MI,** when **coagulative necrosis, neutrophilic infiltration, and lysis of the myocardial connective tissue have appreciably weakened the infarcted myocardium (mean, 4 to 5 days; range, 1 to 10 days).**

Answer 150

The anterolateral wall at the midventricular level is the **most common site for postinfarction free-wall rupture.**

Answer 151

Risk factors for free-wall rupture include: * age over 60, * female gender, * and preexisting hypertension. This complication occurs less frequently in **patients without prior MI because associated fibrotic scarring tends to inhibit myocardial tearing**. Acute free-wall ruptures are usually rapidly fatal. However, a **fortuitously located pericardial adhesion that partially aborts a rupture may result in a false aneurysm (localized hematoma communicating with the ventricular cavity)**. The wall of a false aneurysm consists only of epicardium and adherent parietal pericardium and thus many still ultimately rupture

Answer 152

This complication occurs less frequently in patients without prior MI **because associated fibrotic scarring tends to inhibit myocardial tearing.**

Answer 153

Pericarditis. A fibrinous or fibrinohemorrhagic pericarditis (Dressler syndrome) **usually develops about the second or third day f**ollowing a**transmural infarct as a result of underlying myocardial inflammation**

Answer 154

Right ventricular infarction. Isolated infarction of the right ventricle is unusual, but infarction of some right ventricular myocardium often accompanies ischemic injury of the adjacent posterior left ventricle and ventricular septum. Right ventricular infarcts of either type **cause acute right-sided heart failure associated with pooling of blood in the venous circulation and systemic hypotension**

Answer 155

Infarct extension. ## Footnote **New necrosis may occur adjacent to an existing infarct.**

Answer 156

Infarct extension. ## Footnote **New necrosis may occur adjacent to an existing infarct.**

Answer 157

Infarct expansion. As a result of the weakening of necrotic muscle, there may be **disproportionate stretching, thinning, and dilation of the infarct region (especially with anteroseptal infarcts), which is often associated with mural thrombus (** Fig. 12-19E ).

Answer 158

Mural thrombus. With any infarct, **the combination of a local abnormality in contractility (causing stasis)** and **endocardial damage (creating a thrombogenic surface)** can foster mural thrombosis ( Chapter 4 ) and potentially thromboembolism.

Answer 159

Ventricular aneurysm. In contrast to the false aneurysms mentioned above, **true aneurysms of the ventricular wall are bounded by myocardium that has become scarred.** Aneurysms of the ventricular wall are a **late complication of large transmural infarcts that experience early expansion**. The thin scar tissue wall of an aneurysm paradoxically bulges during systole ( Fig. 12-19F ).

Answer 160

Complications of ventricular aneurysms include: * mural thrombus, * arrhythmias, * and heart failure; * rupture of the tough fibrotic wall is not a concern.

Answer 161

Papillary muscle dysfunction . As mentioned above, rupture of a papillary muscle may **occur following an MI.** More frequently, **postinfarct mitral regurgitation results from ischemic dysfunction of a papillary muscle** and underlying myocardium and later from papillary muscle fibrosis and shortening, or from ventricular dilation (see below).

Answer 162

The risk of specific postinfarct complications and the prognosis depend primarily on the infarct size, location, and thickness (subendocardial or transmural). Large transmural infarcts yield a higher probability of cardiogenic shock, arrhythmias, and late CHF. Patients with anterior transmural infarcts are at greatest risk for free-wall rupture, expansion, mural thrombi, and aneurysm. In contrast, posterior transmural infarcts are more likely to be complicated by conduction blocks, right ventricular involvement, or both; when acute VSDs occur in this area they are more difficult to manage. Overall, however, patients with anterior infarcts have a worse clinical course than those with inferior (posterior) infarcts. With subendocardial infarcts, only rarely do pericarditis, rupture, and aneurysms occur.

Answer 163

In addition to the sequence of repair in the infarcted tissues described above, the **noninfarcted segments of the ventricle undergo hypertrophy and dilation; collectively**, these changes are **termed ventricular remodelin**g. The compensatory hypertrophy of noninfarcted myocardium is initially hemodynamically beneficial. ``` However, this adaptive effect may be overwhelmed by ventricular dilation (with or without ventricular aneurysm) and increased oxygen demand, which can exacerbate ischemia and depress cardiac function. ``` There may also be changes in ventricular shape and stiffening of the ventricle due to scar formation and hypertrophy that further diminish cardiac output. Some of these deleterious effects appear to be reduced by ACE inhibitors, which lessen the ventricular dilation that occurs after MI.

Answer 164

Long-term prognosis after MI depends on many factors, the **most important of which are the quality of residual left ventricular function**and the**extent of vascular obstructions** in vessels that perfuse the viable myocardium. The overall total mortality within the first year is about 30%. Thereafter there is a 3% to 4% mortality among survivors with each passing year. Infarct prevention through control of risk factors in individuals who have never experienced MI (primary prevention) and prevention of reinfarction in those who have recovered from an acute MI (secondary prevention) are important strategies that have received much attention and achieved considerable success.

Answer 165

FIGURE 12-20 Schematic of the various pathways in the progression of ischemic heart disease (IHD), showing the interrelationships among coronary artery disease, acute plaque change, myocardial ischemia, myocardial infarction, chronic IHD, congestive heart failure, and sudden cardiac death.

Answer 166

The designation chronic IHD is used here to describe **progressive heart failure as a consequence of ischemic myocardial damage.**

Answer 167

The term ischemic cardiomyopathy is often used by clinicians to describe chronic IHD. In most instances there has been **prior MI** and **sometimes noninfarcted myocardium**(see earlier discussion of cardiac hypertrophy). However, in **other cases severe obstructive coronary artery disease may present as chronic IHD in the absence of prior infarction**

Answer 168

However, in other cases severe obstructive coronary artery disease may present as chronic IHD in the absence of prior infarction

Answer 169

Morphology. Hearts from patients with chronic IHD are usually **enlarged and heavy**, due to **left ventricular hypertrophy and dilation.** Invariably there i**s some degree of obstructive coronary atherosclerosis.** Discrete scars representing healed infarcts are usually present. The **mural endocardium may have patchy, fibrous thickenings**, and **mural thrombi may be present.**

Answer 170

Microscopic findings include **myocardial hypertrophy,** **diffuse subendocardial vacuolization**, and**fibrosis.**

Answer 171

Clinically, progressive CHF may occur in patients who **have had past episodes of MI or anginal attacks.** In some individuals, however, **progressive myocardial damage is silent, and heart failure is the first indication of IHD**. The diagnosis rests largely on the exclusion of other cardiac diseases. Patients with chronic IHD account for nearly half of cardiac transplant recipients.

Answer 172

Sudden cardiac death (SCD) strikes down about 300,000 to 400,000 individuals annually in the United States. It is **defined as unexpected death** from cardiac causes in i**ndividuals without symptomatic heart disease** or **early after symptom onset (usually within 1 hour).**

Answer 173

SCD is usually the consequence of a **lethal arrhythmia** (e.g.**, asystole, ventricular fibrillation)**. It most frequently occurs in the setting of IHD; in some cases, **SCD is the first clinical manifestation of IHD.**

Answer 174

It most frequently occurs in the setting of IHD; in some cases, **SCD** is the first clinical manifestation of IHD.

Answer 175

**Acute myocardial ischemia** is the most common trigger for fatal arrhythmias . [57] Although ischemic injury can affect the conduction system and create electromechanical cardiac instability, **fatal arrhythmias usually result from acute ischemia-induced electrical instability of** **myocardium** that is distant from the conduction system. Arrythmogenic foci are often located adjacent to scars left by old MIs.

Answer 176

Although **ischemic injury can affect the conduction system** and create electromechanical cardiac instability, **fatal arrhythmias** usually **result from acute ischemia-induced electrical instability of myocardium**that is**distant from the conduction system.**

Answer 177

Arrhythmogenic foci are often located **adjacent to scars left by old MIs.**

Answer 178

* • Congenital structural or coronary arterial abnormalities * • Aortic valve stenosis * • Mitral valve prolapse * • Myocarditis * • Dilated or hypertrophic cardiomyopathy * • Pulmonary hypertension * • Hereditary or acquired cardiac arrhythmias * • Cardiac hypertrophy of any cause (e.g., hypertension) * • Other miscellaneous causes, such as systemic metabolic and hemodynamic alterations, * catecholamines, and drugs of abuse, particularly cocaine and methamphetamine.

Answer 179

Morphology. Marked coronary atherosclerosis with a critical (\>75%) stenosis involving one more of the three major vessels is present in 80% to 90% of SCD victims; only 10% to 20% of cases are of nonatherosclerotic origin. Usually there are high-grade stenoses (\>90%); in approximately one half, acute plaque disruption is observed, and in approximately 25% diagnostic changes of acute MI are seen. [58] This suggests that many patients who die suddenly are suffering an MI, but the short interval from onset to death precludes the development of diagnostic myocardial changes. However, in one study of those who had been successfully resuscitated from a sudden cardiac arrest, a new MI occurred in only 39% of the patients. [59] Thus, **most SCD is not associated with acute MI;** most of these deaths are thought to result from myocardial ischemia–induced irritability that initiates malignant ventricular arrhythmias. **Scars of previous infarcts** and subendocardial myocyte vacuolization indicative of severe chronic ischemia are common in such patients.

Answer 180

Heritable conditions associated with SCD are of importance**, since they may provide a basis for intervention in surviving family members**. [60] Some of these disorders are associated with recognizable **anatomic abnormalities (e.g., congenital anomalies, hypertrophic cardiomyopathy, mitral valve prolapse)**. However, other heritable arrhythmias can precipitate sudden death in the absence of structural cardiac pathology (so-called primary electrical disorders). These syndromes can only be diagnosed definitively by genetic testing, which is performed in those with a positive family history or an unexplained nonlethal arrhythmia.

Answer 181

The primary electrical abnormalities of the heart that predispose to SCD include: * long QT syndrome, * Brugada syndrome, * short QT syndrome, * catecholaminergic polymorphic ventricular tachycardia, * Wolff-Parkinson-White syndrome, * congenital sick sinus syndrome, * and isolated cardiac conduction disease. [61]

Answer 182

The most important of these disorders are the so-called **channelopathies,** which are caused by **mutations in genes that are required for normal ion channel function**. [62] These disorders **(mostly with autosomal-dominant inheritance)** eithe**r involve genes that encode the ion channels (including Na + , K + , and Ca + ),** or **accessory proteins that are essential for the normal function of the same channels**, which are responsible for conducting the electrical currents that mediate contraction of the heart.

Answer 183

T he prototype is the **long QT syndrome**, characterized by **prolongation of the QT segment** in electrocardiograms and susceptibility to malignant ventricular arrhythmias. Mutations in seven different genes account for the majority of cases of long QT syndrome. The most frequent mutations are in the gene encoding KCNQ1 and result in decreased potassium currents. Ion channels are needed for the normal function of many tissues, and certain channelopathies are also associated with skeletal muscle disorders and diabetes; **however, the most common cardiac channelopathies** **are isolated disorders of the heart**

Answer 184

The prognosis of many patients vulnerable to SCD, including those with chronic IHD, is **markedly improved by implantation of a pacemaker or an automatic cardioverter defibrillator,** which **senses and electrically counteracts an episode of ventricular fibrillation.**

Chapter 12: Ischemic Heart Disease Flashcards

(214 cards)