HEART HEART DISEASESDISEASES

HEART DISEASES (HD)HEART DISEASES (HD)

FIVE MAJOR TYPES Ischemic HD Hypertensive HD Valvular/Endocardial HD Cardiomyopathy HD Congenital HD Others: pericarditis, tumor, et al.

ISCHEMIC HEART ISCHEMIC HEART DISEASEDISEASE

Myocardial ischemia Myocardial ischemia is a condition in which oxygen deprivation to the heart muscle is accompanied by inadequate removal of metabolites because of reduced blood flow or perfusion.

Ischemic Heart DiseaseIschemic Heart Disease

Ischemic heart disease (IHD) is the generic designation for a group of closely related syndromes resulting from ischemia–an imbalance between the supply and demand of the heart for oxygenated blood.

.

An imbalance occurs between myocardial oxygen supply and demand.

“Supply” ischemia Acute reduction of oxygen supply secondary to

increased coronary vascular tone (ie, coronary vasospasm) or by marked reduction or cessation of coronary flow as a result of platelet aggregates or thrombi.

Responsible for myocardial infarction (MI) Most episodes of unstable angina (UA) In many circumstances, ischemia results from

both an increase in oxygen demand and a reduction in supply.

“Demand" ischemiaIn the presence of coronary obstruction,

an increase of myocardial oxygen requirements caused by exercise, tachycardia, or emotion leads to a transitory imbalance.

Responsible for most episodes of chronic stable angina

Ischemia may manifest as (1) anginal discomfort, (2) ST-segment deviation on ECG, (3) reduced uptake of thallium 201 or

technetium 99 in myocardial perfusion images,

(4) regional or global impairment of ventricular function.

Supply Demand

Supply

Demand

Determinants of myocardial oxygen consumption Heart rate Contractility Systolic wall tension Maintenance of cell viability in basal state Depolarization Activation Maintenance of active state Direct metabolic effect of catecholamines Fatty acid uptake

Ischemia comprises not only insufficiency of oxygen (hypoxia, anoxia), but also reduced availability of nutrient substrates and inadequate removal of metabolites.

Because coronary artery narrowing or obstruction owing to atherosclerosis underlies myocardial ischemia in the vast majority of cases, IHD is often termed coronary artery disease (CAD) or coronary heart disease (CHD).

The acute coronary syndromes of unstable angina, acute myocardial infarction, and sudden death

share a common pathophysiologic basis, with coronary atherosclerotic plaque rupture as the pathologic hallmark and associated intraluminal platelet-fibrin thrombus.

The dominant influence in the causation of the IHD syndromes :

Fixed atherosclerotic narrowing of the coronary arteries,

Intraluminal thrombosis overlying a ruptured or fissured atherosclerotic plaque,

Platelet aggregation, Vasospasm.

Role of Fixed Coronary ObstructionsRole of Fixed Coronary Obstructions

More than 90% of patients with IHD have advanced stenosing coronary atherosclerosis (“fixed” obstructions).

Although only a single major coronary

epicardial trunk may be affected, more often two or all three are involved .

Role of Acute Plaque ChangeRole of Acute Plaque Change Acute myocardial ischemia is often precipitated by

disruption of previously only partially stenosing atherosclerotic plaques with hemorrhage, fissuring, or ulceration.

This is often followed by mural or total thrombosis. Such vascular injury is fundamental to the

development of the acute coronary syndromes–unstable angina, acute myocardial infarction, or sudden ischemic death–in most patients.

High-grade but slowly developing occlusions probably stimulate well-developed collateral vessels over time that may protect against infarction.

Role of Coronary ThrombusRole of Coronary Thrombus

Coronary thrombosis, partial or total, plays a critical role in acute coronary syndromes.

In myocardial infarction, the added thrombus converts a disrupted, partially stenotic plaque to a complete stenosis.

Thrombus is a potent activator of multiple growth-related signals in smooth muscle cells; both platelet-mediated and smooth muscle cell-mediated events contribute to the growth of atherosclerotic lesions.

Role of VasoconstrictionRole of Vasoconstriction

Transient vasoconstriction may be induced at a site of plaque disruption and thrombosis.

Terminology: Ischemic Heart Disease

• Ischemia - Insufficient blood supply injury Angina (reversible) or MI (irreversible)

• Angina (Angina=Strangulation Pectoris=Chest)

• Myocardial infarction (MI) - Death of myocardial cells (irreversible)

• Cardiac failure : Impaired pumping ability of the heart

• Cardiogenic shock : Shock due to cardiac failure

• Arrhythmias: cardiac rhythm disturbances

Coronary circulationCoronary circulation Rich Blood supply High Oxygen consumption (A-V19-9ml/100ml)

Two coronary arteries-225 ml/min Direct branch from aorta End arteries – few collaterals Phasic blood flow- during diastole Local metabolism is primary controller of

coronary blood flow

Coronary Coronary ArteriesArteries

Right Coronary Artery

LCx

LAD

Left Coronary Artery

•Anterior Descending

•Circumflex

Abnormalities of OAbnormalities of O22 supply supply

Increased O2 demandHigh heart rate, BP, Contractility

Insufficient O2 supplyAnemia and Hypoxia

Coronary VesselsIntermittent (Spasm, Congenital)Permanent (Atherosclerotic Plaque)

Depending on the rate of development and ultimate severity of the arterial narrowing(s) and the myocardial response, four ischemic syndromes may result:

(1) angina pectoris

(2) myocardial infarction

(3) chronic ischemic heart disease

(4) sudden cardiac death

IIschemic syndromesschemic syndromes

1. Angina Pectoris

Stable (classic, typical, Heberden) angina

Unstable (pre-infarction, crescendo, acute coronary insufficiency) angina

Prinzmetal's ("variant") angina

Anginas are caused by varying combinations of increased myocardial demand and decreased myocardial perfusion, owing to

fixed stenosing plaques disrupted plaques vasospasm thrombosis platelet aggregation embolization

Angina pectoris is a symptom complex of IHD characterized by paroxysmal attacks of

substernal or precordial chest discomfort (variously described as

constricting, squeezing, choking, or knife-like)

Caused by transient (15 seconds to 15 minutes) myocardial ischemia that falls short of inducing the cellular necrosis that defines infarction.

Stable (classic, typical, Heberden) angina

The pathogenesis of typical angina pectoris appears to be the reduction of coronary perfusion to a critical level by chronic stenosing coronary atherosclerosis.

This renders the heart vulnerable to further ischemia whenever there is increased demand, such as that produced by physical activity, emotional excitement, or any other cause of increased cardiac workload.

Relieved by rest or nitroglycerin, a strong coronary vasodilator (thereby increasing supply).

Unstable (pre-infarction, crescendo, acute coronary insufficiency) angina

Refers to a pattern of pain that occurs with progressively increasing frequency, is precipitated with progressively less effort, often occurs at rest, and tends to be of prolonged duration.

In most cases, this is probably due to a thrombus developing over a ruptured plaque.

In unstable angina, a relatively small fissure or disruption of an atherosclerotic plaque may lead to a sudden change in plaque morphology, with platelet aggregation or mural thrombus and frequently vasoconstriction leading to transient reduction in coronary blood flow.

Untreated, many of these people get an MI soon.

Prinzmetal's ("variant") angina

This is primarily attributable to vasospasm. Perhaps it's the cardiac equivalent of migraine. Although individuals with this form of angina may well

have significant coronary atherosclerosis, the anginal attacks are generally unrelated to physical activity, heart rate, or blood pressure.

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

2. Myocardial Infarction“Heart attack”

• Death of Myocardial muscle due to lack of blood supply.

• Most common cause is Atherosclerotic narrowing of coronary arteries.

Pain in Myocardial InfarctionPain in Myocardial Infarction

Precordial , intense, constrictive Similar to Angina – severe prolonged Radiates to shoulder and left arm May present in other location-jaw,

epigastrium. Often with breathlessness, nausea,

vomiting & perspiration Hypotension Collapse Less severe or absent in elderly No response to nitrates

Causes of myocardial infarctsCauses of myocardial infarcts

Atherosclerosis: Makes up 90% of coronary artery disease Cocaine: The second most common cause of myocardial

infarction and sudden cardiac death Prinzmetal's coronary spasm Vasculitis: (1) lupus; (2) polyarteritis nodosa; (3)

rheumatoid arthritis; (4) Kawasaki's; (5) Takayasu's; (6) mycotic aneurysms.

Embolization Syphilis (mesaortitis syphilitica) Dissecting hematoma Shock and left-sided failure (subendocardial infarct )

There are two types of myocardial infarction, each having differing morphology and clinical significance:

(1) The transmural infarct (more common type)

(2) The subendocardial (nontransmural) infarct

TThe transmural infarcthe transmural infarct

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

coronary atherosclerosis plaque rupture superimposed thrombosis

Subendocardial InfarctionSubendocardial Infarction

An area of ischemic necrosis limited to the inner one-third or at most one-half of the ventricular wall, often extending laterally beyond the perfusion territory of a single coronary artery.

There is diffuse stenosing coronary atherosclerosis and global reduction of coronary flow but neither plaque rupture nor superimposed thrombosis.

Coronary Arterial OcclusionCoronary Arterial Occlusion

At least 90% of transmural acute myocardial infarcts are caused by an occlusive intracoronary thrombus overlying an ulcerated or fissured stenotic plaque.

Every acute transmural myocardial infarct, a dynamic interaction has occurred among several or all of the following: severe coronary atherosclerosis, an acute atheromatous

plaque change (fissuring, ulceration), superimposed thrombosis, platelet activation, and vasospasm.

In the typical case, the following sequence of events can be proposed (90%):

Sudden change in the morphology of an atheromatous plaque, i.e., intraplaque hemorrhage, ulceration, or fissuring.

Platelet adhesion, aggregation, activation, and release of adenosine diphosphate (ADP), with buildup of a platelet mass. The platelet mass may give rise to emboli or potentiate occlusive thrombosis.

Tissue thromboplastin is released. Adherent activated platelets release thromboxane A2,

serotonin, and platelet factors 3 and 4 (predisposing to coagulation, favoring vasospasm).

Frequently within minutes, the thrombus evolves to become completely occlusive.

In the approximately 10% of casesIn the approximately 10% of cases

In some of the cases, the coronary arteries are free of atherosclerosis by angiography:

Vasospasm with or without coronary atherosclerosis may induce the acute perfusion deficit, perhaps in association with platelet aggregation.

Emboli from a left-sided mural thrombosis or vegetative endocarditis or paradoxic emboli from the right side of the heart or the peripheral veins (through a patent foramen ovale) could cause coronary occlusion.

Coronary AtheorsclerosisCoronary Atheorsclerosis

Right Coronary Artery

LCx

LAD

Coronary AtheorsclerosisCoronary Atheorsclerosis

Myocardial Infarction : Myocardial Myocardial Infarction : Myocardial

ResponseResponse

Occlusion of a major coronary artery results in ischemia throughout the anatomic region supplied by that artery (called area at risk),

Acutely ischemic myocardium undergoes progressive biochemical, functional, and morphologic changes, the outcome of which largely depends on the severity and duration of flow deprivation.

The principal biochemical consequence of myocardial ischemia is the onset of anaerobic glycolysis within seconds, leading to inadequate production of high-energy

phosphates (e.g., creatine phosphate and adenosine triphosphate [ATP ]) and accumulation of potentially noxious breakdown products (such as lactic acid).

Myocardial function is exceedingly sensitive to severe ischemia; striking loss of contractility is evident within 60 seconds of onset.

Reversible ultrastructural changes develop within few minutes after onset of ischemia e.g., cell and mitochondrial swelling, glycogen

depletion. Although function becomes strikingly abnormal

within few minutes after onset of ischemia, myocardial coagulation necrosis occurs only after 20 to 40 minutes of severe ischemia.

Irreversible injury of ischemic myocytes occurs first in the subendocardial zone.

With more extended ischemia, a wavefront of cell death moves through the myocardium to involve progressively more of the transmural thickness of the ischemic zone.

The precise location, size, and specific morphologic features of an acute myocardial infarct depend on:

(1) the location, severity, and rate of development of coronary atherosclerotic obstructions;

(2) the size of the vascular bed perfused by the obstructed vessels; (3) the duration of the occlusion; (4) the metabolic/oxygen needs of the myocardium at risk; (5) the extent of collateral blood vessels; (6) the presence, site, and severity of coronary arterial spasm; (7) other factors

such as alterations in blood pressure, heart rate, and cardiac rhythm.

LOCATIONLOCATIONThe corresponding sites of myocardial lesions:The corresponding sites of myocardial lesions:

Left anterior descending coronary artery (40 to 50%): Anterior wall of left ventricle near apex Anterior two-thirds of interventricular septum

Right coronary artery (30 to 40%): Inferior/posterior wall of left ventricle Posterior one-third of interventricular septum Posterior right ventricular free wall in some cases

Left circumflex coronary artery (15 to 20%): Lateral wall of left ventricle

1.Left anterior descending: Anterior wall, anterior 2/3 of septum, apex (40-50%)

2.Right: Posterior-inferior wall, posterior 1/3 of septum (30-40%)

3.Left circumflex: Lateral wall (15-20%)

Classically, the coronary arteries have the following distribution, and their occlusion will result in transmural infarcts in the corresponding distribution

Several infarcts of varying age in the same heart are frequently found.

Repetitive necrosis of adjacent regions yields progressive extension of an individual infarct over a period of days to weeks–“stuttering infarct.”

Examination of the heart in such cases often reveals a central zone of infarction that is days to weeks older than a peripheral margin of more recent ischemic necrosis.

SStuttering infarcttuttering infarct

Areas of damage undergo a progressive sequence of changes that consist of typical ischemic coagulative necrosis, followed by inflammation and repair.

The appearance of an infarct at autopsy depends on the duration of survival of the patient following myocardial infarction onset.

Early recognition of acute myocardial infarcts by pathologists is a difficult problem:particularly when death has occurred within minutes to

a few hours after the onset of the ischemic injury, because diagnostic morphologic changes lag behind the actual injury.

Macroscopical findingsMacroscopical findings

Myocardial infarcts less than 6 to 12 hours old are usually inapparent on gross examination.

It is often possible, however, to highlight the area of necrosis by histochemical changes that first become apparent after 2 to 3 hours.

Immersion of tissue slices in a solution of triphenyltetrazolium chloride (TTC) imparts a brick-red color to intact, noninfarcted myocardium where the dehydrogenase enzymes are preserved. Because dehydrogenases are depleted in the area of ischemic

necrosis (i.e., they leak out through the damaged cell membranes), an infarcted area is revealed as an unstained pale zone (especially apparent after fixation, when unstained myocardium appears light brown).

By 12 to 48 hours, the lesion can be identified in routinely fixed gross slices (including those not stained with TTC) because of either pallor or a red-blue hue owing to the stagnated, trapped blood. Progressively thereafter the infarct becomes a more sharply defined yellow zone.

Within10 days to 2 weeks the there is a softened area rimmed by a hyperemic zone of highly vascularized granulation tissue.

Over the succeeding weeks, the injured region evolves to a fibrous scar.

Microscopical findingsMicroscopical findings

Using light microscopy of sections stained by routine tissue stains, the typical microscopic changes of coagulative necrosis are not detectable for at least the first 4 to 12 hours.

“Wavy fibers” may be present at the periphery of the infarct; it is thought that these changes result from the

forceful systolic tugs by the viable fibers immediately adjacent to the noncontractile dead fibers, stretching and buckling them.

Duration Macro Micro

0-30 m None Loss of glycogen (EM)

4-8 h None EM: Earliest nuclear changes, Wavy fibers

8-12 h None Contraction bands

12-48 h Sharply defined yellow lesion, Edema

Necrosis,

Acute inflammation

3-7 D Hyperemia and Hemorrhage

Early findings of Granulation tissue

1-3 W Thin, yellow Granulation tissue,

Early fibrosis

3-7 W Tough white Dense Fibrosis

MorphologyMorphology

Coronary Coronary Thrombosis Thrombosis With InfarctionWith Infarction

Coronary AtherosclerosisCoronary Atherosclerosis

Coronary Atherosclerosis with ThrombosisCoronary Atherosclerosis with Thrombosis

Myocardial Infarction – 3Myocardial Infarction – 3 dd

Myocardial Infarction – Myocardial Infarction – 1 W1 W

Myocardial Infarction – Myocardial Infarction – 22 WW

Myocardial Infarction – Myocardial Infarction – 33 WW

Myocardial InfarctionMyocardial Infarction – 5 W – 5 W

Normal MyocardiumNormal Myocardium

MI MI 1212-4-488 hr hr

loss of nucleus, contaction bands, coagulative necrosisloss of nucleus, contaction bands, coagulative necrosis..

Contraction bands (myofibrillar degeneration) densely eosinophilic cross-bands which probably result from calcium entering membrane-damaged cells during reperfusion. Contraction bands let you know that a sudden death is of cardiac ischemic origin.

Contraction bands can probably result from epinephrine administration and/or electric shocks in CPR.

MI 3-4 dayMI 3-4 day

MI 1MI 1st st wweekeek

MI 2-MI 2-33 W W

MI >MI >33--77 W W Collagen ScarCollagen Scar

If the patient with acute myocardial infarction reaches the If the patient with acute myocardial infarction reaches the hospital, the likelihood of the most serious complications is as hospital, the likelihood of the most serious complications is as follows:follows:

Uncomplicated cases (10 to 20% of cases) Complicated cases (80 to 90% of cases):

Arrhythmias and conduction defects (75-95% of complicated cases)

Extension of infarction, or re-infarction Left-sided Congestive heart failure (pulmonary edema) Cardiogenic shock (10-15%; high mortality ~70% sudden

death) Dressler's pericarditis/postpericardiotomy syndrome

(occurs weeks after an MI or cardiac surgery) Mural thrombosis, embolization Myocardial wall rupture (tamponade) Septum rupture (left-to-right shunt) Papillary muscle rupture (mitral regurgitation) Ventricular aneurysm Chronic ischemic heart disease

Cardiogenic shockCardiogenic shock

Severe “pump failure” (cardiogenic shock), which occurs in 10 to 15% of patients following myocardial infarction

Generally indicates a large infarct (often greater than 40% of the left ventricle)

Cardiogenic shock has a nearly 70% mortality rate and accounts for two-thirds of in-hospital deaths

RuptureRupture

The cardiac rupture syndromes result from the mechanical weakening that occurs in necrotic and subsequently inflamed myocardium and include ;

(1) rupture of the ventricular free wall (most commonly), usually with hemopericardium and cardiac tamponade,

(2) rupture of the interventricular septum (less commonly), leading to a left-to-right shunt;

(3) papillary muscle rupture (least commonly), resulting in the acute onset of severe acute mitral regurgitation.

MI - RuptureMI - Rupture

TTamponadeamponade

PericarditisPericarditis A fibrinous or fibrinohemorrhagic pericarditis usually

develops about the second or third day. It is most often localized to the region overlying the

necrotic area and usually resolves with healing of the infarct.

Pericarditis is the epicardial manifestation of the inflammation elicited by a direct underlying transmural infarct.

AneurysmAneurysm

The clinical and laboratory diagnosis of The clinical and laboratory diagnosis of acute myocardial infarctionacute myocardial infarction

Creatinine Kinase

CK- Isoenzymes (Fractions)

Troponins - I & T.

LDH - 1-5 (1 - 2 flip)

Myoglobin

• Symptoms• ECG changes• Elevations of specific

serum enzymes

3. Chronic Ischemic Heart Disease3. Chronic Ischemic Heart Disease The designation chronic ischemic heart

disease (CIHD) is used here for the hearts in patients, often but not exclusively elderly, who insidiously develop CHF, sometimes fatal, as a consequence of ischemic myocardial damage.

There has been a history of angina and usually prior episodes of myocardial infarction, often as remote as 5 to 10 years before the onset of the CHF.

MorphologyMorphology The pericardial surface of the heart in CIHD may have

adhesions as a result of healing of pericarditis associated with past myocardial infarcts.

Invariably there is moderate to severe stenosing atherosclerosis of the coronary arteries and sometimes total occlusions resulting from organized thrombi.

Discrete, gray-white scars of healed previous infarcts are usually present.

The mural endocardium is generally normal except for some superficial, patchy, fibrous thickenings.

The major microscopic findings includediffuse myocardial atrophysubendocardial vacuolizationdiffuse, interstitial and patchy replacement

fibrous tissuelarge healed scars of previous acute infarcts.

Chronic Ischemic Heart Disease Can Lead to Cardiomyopathy In a minority of patients with severe coronary

atherosclerosis, myocardial contractility is impaired globally without discrete infarcts, as in dilated cardiomyopathy.

This situation usually reflects a combination of • ischemic myocardial dysfunction, • diffuse fibrosis, • multiple small healed infarcts.

Ischemic cardiomyopathy.

4. Sudden cardiac death4. Sudden cardiac death Most commonly sudden cardiac death (SCD) is defined as

unexpected death from cardiac causes early (usually within 1 hour) after or without the onset of symptoms.

In the vast majority of cases in adults, SCD is a complication and often the first clinical manifestation of IHD. Less frequently SCD is caused by

• a congenital structural abnormality• aortic valve stenosis• hereditary or acquired abnormalities of the cardiac conduction

system• mitral valve prolapse• myocarditis• idiopathic dilated or hypertrophic cardiomyopathy

MorphologyMorphology

The ultimate mechanism of death is almost always a lethal arrhythmia (e.g., asystole, ventricular fibrillation). Long-standing coronary atherosclerosis

with diffuse myocardial atrophy, Interstitial fibrosis, Possibly healed infarcts.

They can impinge on the conduction system and create electromechanical cardiac instability.

In most cases, however, acute myocardial ischemia with or without plaque fissuring or myocardial infarction induces irritability of myocardium distant from the conduction system and triggers the fatal arrhythmia.

Marked coronary atherosclerosis with critical (greater than 75%) stenosis involving more than one of the three major vessels is present in 80 to 90% of victims; only 10 to 20% of cases are of nonatherosclerotic origin.

Usually there are high-grade stenoses (greater than 90%).

The precise frequency of acute coronary changes (i.e., thrombosis, plaque fissuring, intraplaque hemorrhage) are common (75 to 80%).

A healed myocardial infarct is present in about 40%, but in those who have been rescued by prompt therapy from sudden cardiac arrest, new myocardial infarction is found in 25% or less.

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