Myocardial Infarction and its Complications

REZA KIANI ,MD, Invasive Cardiologist & Interventionist Rajaei Heart Center

Coronary artery disease is the leading cause of mortality in modern societies and is a worldwide epidemic.

In 2001, it was estimated that worldwide, ischemic heart disease was responsible for 11.8 percent of all deaths (5.7 million) in low-income countries and 17.3 percent (1.36 million) of all deaths in high-income countries.

Acute Myocardial Infarction (MI) is the most common cause of fatality in the family of coronary artery disease.

Despite revolutionary improvements in the treatment of this catastrophic disease, AMI continues to be a serious public health problem

it has been estimated that the number of years of life lost because of an AMI is 14.2 years.

the cost to American society (both direct and indirect) is $142.5 billion per year.

Introduction

Observational data bases suggest that 30-day mortality rate in MI patients in the community is 15 to 20 percent .

The mortality rate of patients with STEMI who receive an appropriate pharmacological or invasive therapy is in the range of 5.5 to 7.5 percent.

So, appropriate therapy causes 9-12% improvement in survival in 30 days. Impressive!!

Mortality rate

The pathological diagnosis of myocardial infarction (MI) :evidence of myocyte cell death as a consequence of prolonged ischemia. Characteristic findings include coagulation necrosis and contraction band necrosis, often with patchy areas of myocytolysis at the periphery of the infarct.

the majority of myocyte loss in the infarct zone occurs via coagulation necrosis and proceeds to inflammation, phagocytosis of necrotic myocytes, and repair eventuating in scar formation.

Definition of MI

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

Pathology

Pathology During the natural evolution of

atherosclerotic plaque, especially lipid laden plaque, an abrupt transition can occur, characterized by plaque disruption .

Plaque disruption exposes substances that promote platelet activation and aggregation, thrombin generation, and ultimately thrombus formation.

The resultant thrombus interrupts blood flow and leads to an imbalance between oxygen supply and demand and, if this imbalance is severe and persistent, to myocardial necrosis

Activated macrophages and mast cells abundant at the site of atheromatous plaque are an important cause of rupture. These cells overexpress metalloproteinase enzymes such as collagenase, gelatinase, and stromelysin that degrade components of the protective extracellular matrix such as collagen, elastin and glycoproteins.

In addition, stresses induced by intraluminal pressure, tachycardia (cyclic stretching and compression), and disruption of nutrient vessels combine to produce plaque disruption .

Plaques always disrupt at the margin of the fibrous cap near an adjacent, less involved segment of the coronary artery wall (shoulder region of plaque)

Why an atherosclerotic plaque ruptures?

Vulnerable Plaque

Platelet aggregation to the surface of ulcerated plaque is the first step of thrombus formation

After that, the platelets release ADP, thrombin, serotonin, epinephrin which causes fibrin formation, entrapment of red blood cells and propagation of the early thrombus.

After disruption

The composition of the thrombus may vary at different levels: A white thrombus is composed of platelets, fibrin, or both, and a red thrombus is composed of erythrocytes, fibrin, platelets, and leukocytes.

Early thrombi are usually small and non-occlusive and are composed predominantly of platelets.

Occlusive thrombi and propagation of early thrombus are predominantly red thrombus.

Thrombus propagation

On gross inspection, myocardial infarction can be divided into two major types: transmural infarcts, in which myocardial necrosis involves the full thickness (or nearly full thickness) of the ventricular wall, and subendocardial (nontransmural) infarcts, in which the necrosis involves the subendocardium and inner part of intramural myocardium, without extending all the way through the ventricular wall .

Gross pathology

An occlusive coronary thrombosis appears to be far more common when the infarction is transmural .

Nontransmural infarctions, however, frequently occur in the presence of severely narrowed but still patent coronary arteries.

THE FIRST HOURS. Gross alterations of the myocardium are difficult to identify until at least 6

to 12 hours have elapsed following the onset of necrosis THE FIRST DAYS. Eighteen to 36 hours after the onset of the infarct, the myocardium is

reddish purple (because of trapped erythrocytes), with a serofibrinous exudate evident on the epicardium in transmural infarcts. These changes persist for approximately 48 hours; the infarct then turns gray, and fine yellow lines, secondary to neutrophilic infiltration, appear at its periphery. This zone gradually widens and during the next few days extends throughout the infarct.

THE FIRST WEEKS. Eight to 10 days after infarction, the thickness of the cardiac wall in the

area of the infarct is reduced as necrotic muscle is removed by mononuclear cells. The cut surface of an infarct of this age is yellow, surrounded by a reddish purple band of granulation tissue that extends through the necrotic tissue by 3 to 4 weeks. Commencing at this time and extending over the next 2 to 3 months, the infarcted area gradually acquires a gelatinous, ground-glass, gray appearance, eventually converting into a shrunken, thin, firm scar, which whitens and firms progressively with time

Gross pathology cont.

COAGULATION NECROSIS. Coagulation necrosis is usually present in the central region of

infarcts, which results in the arrest of muscle cells in the relaxed state and the passive stretching of ischemic muscle cells. no calcification is evident.

NECROSIS WITH CONTRACTION BANDS. This form of myocardial necrosis, also termed contraction band

necrosis or coagulative myocytolysis, results primarily from severe ischemia followed by reflow. It is characterized by hypercontracted myofibrils with contraction bands and mitochondrial damage, frequently with calcification. Necrosis with contraction bands is caused by increased Ca2+ influx into dying cells, resulting in the arrest of cells in the contracted state. It is seen in the periphery of large infarcts and is present to a greater extent in nontransmural than in transmural infarcts.

MYOCYTOLYSIS. Ischemia without necrosis generally causes no acute changes that

are visible by light microscopy. However, severe prolonged ischemia can cause myocyte vacuolization, often termed myocytolysis. Prolonged severe ischemia causes hydropic, vascular, and fatty degeneration.

Patterns of myocardial necrosis

coagulative necrosis at day 1

polymorphonuclear leukocytic infiltrate in an area of acute myocardial infarction of 3 to 4 days' duration

Nearly complete removal of necrotic myocytes by phagocytosis (â≈7 to 10 days).

Granulation tissue with a rich vascular network and early collagen deposition, approximately 3 weeks after infarction

replacement of the necrotic fibers by dense collagenous scar

Necrosis with contraction bands

Effect of reperfusion ,either spontaneous or as part of therapy

Pathophysiology

Pathophysiology Systolic function: Upon

interruption of antegrade flow in an epicardial coronary artery, the zone of myocardium supplied by that vessel immediately loses its ability to shorten and perform contractile work.

3 abnormal contraction patterns develop in sequence: (1) hypokinesis, reduction in the extent of shortening; (2) akinesis, cessation of shortening; and (3) dyskinesis, paradoxical expansion, and systolic bulging.

If a sufficient quantity of myocardium undergoes ischemic injury, left ventricular pump function becomes depressed; cardiac output, stroke volume, blood pressure.

Reduced cardiac output causes: hypotension & shock, hypoperfusion of visceral organs ( kidney, GI tract, Liver) and if severe enough perfusion of heart and CNS also will decrease.

Diastolic function: relaxation of heart muscle is an active and energy-

dependent process. So, in ischemia, relaxation of the heart is compromised just like the contraction .

impaired diastolic function causes backward heart failure : increased LV diastolic pressure increases pulmonary artery venous pressure and capillary pressure( pulmonary wedge pressure). Increased pulmonary capillary pressure causes extravasation of plasma into to pulmonary interstitial and alveolar space.

Fluid in the interstitial and alveolar space causes dyspnea, orthopnea, hypoxemia and if severe a life-theatening condition: ACUTE PULMONARY EDEMA

After the acute phase The most important sequela of MI in long term is

: reduced ejection fraction and heart failure. MI is the most common cause of heart failure in

the community. Infarctions which involve the anterior and septal

portions of the left venricle reduce EF more than those involving inferior or postero-lateral region.

Myocardial loss < 10-15% no symptomatic HF, 10-25% : mild to moderate HF, 25-40% severe HF, > 40% cardiogenic shock & possibly death.

Electrocardiographic changes in MI

EKG is one of the most important diagnostic tools in the acute phase of MI and also is probably the most important part of defining the strategy of treatment, the success of therapy and the prognosis.

The earliest and most consistent electrocardiographic finding during acute ischemia is deviation of the ST segment as a result of a current of injury mechanism. Under normal conditions, the ST segment is usually nearly isoelectric

Mechanism: Severe acute ischemia can reduce the resting membrane potential, shorten the duration of the action potential in the ischemic area. These changes cause a voltage gradient between normal and ischemic zones that leads to current flow between these regions. These currents of injury are represented on the surface ECG by deviation of the ST segment.

When acute ischemia is transmural the overall ST vector is usually shifted in the direction of the outer (epicardial) layers, and ST elevation and sometimes tall positive (hyperacute) T waves are produced over the ischemic zone . When ischemia is confined primarily to the subendocardium, the overall ST vector typically shifts toward the inner ventricular layer and the ventricular cavity, such that the overlying (e.g., anterior precordial) leads show ST segment depression with ST elevation in lead aVR

ST-elevation MI As it is mentioned, transmural MI is always

accompanies ST elevation in surface EKG.depending on the territory of MI, ST elevation differs

In anterior wall MI: V2-V5 and I, aVL may have ST elevation

In Inferior wall MI: II, III, aVF may have ST elevation.

These leads are called contiguous leads.

Reciprocal ST depression In ST-elevation MI, Reciprocal ST

depressions can appear in leads sensing the contralateral surface of the heart.

For example in Anterior wall trans-mural MI, reciprocal ST depression may be observed in II, III, aVF and in Inferior wall MI in V2-V6 or I, aVL.

ST elevation as a marker of viable myocardium When ST elevation is present it means that

the myocardium is affected by severe ischemia and there is a time window of 6-12 hours before the irreversible necrosis occures. So, as far as the ST elevation is visible, most of the myocardial mass is alive.

During this golden time, pharmocologic or mechanical reperfusion therapy will save the myocardium and prevents consequent complications.

Sometimes the first EKG finding in STEMI is tall T wave (hyperacute T wave).

This tall T wave will always evolve to ST elevation in the affected leads

After 12 hours If no reperfusion occurs in the occluded

coronary artery territory, ST elevation will resolve after nearly 12 hours and a prominent Q wave plus T wave inversion will be seen in that territory.

Some degrees of ST elevation may persist in the subacute phase and this is a sign of severe dyskinesia or aneurysm formation in that territory.

A small R (embryonic R) may appear before Q wave

T wave inversion may persist forever or it may become upright after months or years of the event but the Q wave in the affected territory will remain for life time.

Q wave is the EKG SCAR of STEMI !!

No ST Elevation ST Elevation

Acute Coronary Syndrome

Uns Angina NQMI Qw MI

NSTEMI

Myocardial Infarction

UA/NSTEMI 9/00

Clinical manifestations

In up to half of patients with STEMI, a precipitating factor or prodromal symptoms can be identified. Evidence suggests that unusually heavy exercise (particularly in fatigued or habitually inactive patients) and emotional stress can precipitate STEMI.

In some patients unstable angina is the precursor of MI. Accelerating angina and rest angina, two patterns of unstable angina, may culminate in STEMI.

Other precipitating factors: non-cardiac surgery; respiratory infections; hypoxemia of any cause; pulmonary embolism; hypoglycemia; administration of ergot preparations; use of cocaine; sympathomimetics; serum sickness; allergy; and, on rare occasion, wasp stings.

Circadian periodicity: The time of onset of STEMI has a pronounced circadian periodicity, with peak incidence of events between 6 am and noon.[80] Circadian rhythms affect many physiological and biochemical variables; the early morning hours are associated with rises in plasma catecholamines and cortisol and increases in platelet aggregability.

Seasonal periodicity: MI is more prevalent in cold months of winter or in very warm and humid weathers.

In most patients, it is severe and in some instances intolerable. The pain is prolonged, usually lasting for more than 30 minutes and frequently for a number of hours.

The discomfort is described as constricting, crushing, oppressing, or compressing; often the patient complains of a sensation of a heavy weight or a squeezing in the chest.

The pain is usually retrosternal in location, spreading frequently to both sides of the anterior chest, with predilection for the left side.

In some instances the pain of STEMI may begin in the epigastrium and simulate a variety of abdominal disorders, a fact that often causes STEMI to be misdiagnosed as “indigestion.”

In other patients, the discomfort of STEMI radiates to the shoulders, upper extremities, neck, jaw, and interscapular region, again usually favoring the left side.

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

Nature of pain

Nausea and vomiting may occur, presumably because of activation of the vagal reflex or stimulation of left ventricular receptors as part of the Bezold-Jarisch reflex. These symptoms occur more commonly in patients with inferior STEMI than in those with anterior STEMI.

When the pain of STEMI is epigastric in location and is associated with nausea and vomiting, the clinical picture can easily be confused with that of acute cholecystitis, gastritis, or peptic ulcer.

Other symptoms include feelings of profound weakness, dizziness, palpitations, cold perspiration, and a sense of impending doom.

On occasion, symptoms arising from an episode of cerebral embolism or other systemic arterial embolism herald a STEMI.

Other symptoms

15% will have myocardial infarction

30-35% will have acute coronary syndrome (unstable angina)

45-50% will have non-cardiac pain

Patients with chest pain

DIFFERENTIAL DX of severe chest discomfort Acute myocardial infarction (STEMI vs Non

STEMI) Acute coronary syndrome (ACS) Aortic dissection Pulmonary embolus Pericarditis Pneumonia Gastroesophageal reflux (GERD) Musculoskeletal Psychosocial

Lab data

The classic World Health Organization (WHO) criteria for the diagnosis of MI: at least two of the following three elements be present:

1.a history of ischemic-type chest discomfort, 2.evolutionary changes on serially obtained ECG tracings,

3. a rise and fall in serum cardiac markers

Total serum Creatine phosphokinase ( CPK ) activity

Serum Lactate DeHydrogenase ( LDH ) level Serum Aspartate trans aminase ( AST ) &

Aldehyde trans aminase ( ALT ) many isoenzymes, abundant in many other

organs, many false positive results Their use is a class III indication in AHA

guidelines (contraindicated)

Historical practice

Creatine Kinase isoenzyme MB Cardiac Troponin I, T Serum Myoglobin

Today’s practice

3 isoenzymes: MM, BB, MB Brain & Kidney : BB Skletal muscle : 97% MM, 3% MB Heart muscle: MM, MB So, MB isoenzyme is predominantly present in

myocardium although small quantities are found in : skeletal muscle, small intestine, tongue, diaphragm, uterus, and prostate.

Serum CK activity exceeds the normal range within 4 to 8 hours after the onset of STEMI and declines to normal within 2 to 3 days

CK isoenzymes

CARDIAC-SPECIFIC TROPONINS

Both TnT and TnI are present in cardiac and skeletal muscle,but they are encoded by different genes and their amino acid sequence differs. This permits the production of antibodies that are specific for the cardiac form (cTnT and cTnI)

In patients with MI, cTnT and cTnI first begin to rise above the upper reference limit by 3 hours from the onset of chest pain. Because of a continuous release from a degenerating contractile apparatus in necrotic myocytes, elevations of cTnI may persist for 7 to 10 days after MI; elevations of cTnT may persist for up to 10 to 14 days.

The prolonged time course of elevation of cTnT and cTnI is advantageous for the late diagnosis of MI

Patients with STEMI who undergo successful recanalization of the infarct-related artery have a rapid release of cardiac troponins that also may be useful as an indicator of reperfusion.

Myoglobin This monomeric heme protein is released into the

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

Peak levels of serum myoglobin are reached considerably earlier than peak values of serum CK.

Because of its lack of cardiac specificity, an isolated measurement of myoglobin in patients with a nondiagnostic ECG should not be relied on to make the diagnosis of MI but should be supplemented by a more cardiac-specific marker such as cTnI or cTnT.

Troponin Vs CK MB Troponin is more sensitive: troponin assays can

probably detect episodes of myocardial necrosis that are below the detection limit of the current CK-MB assays.

Detection of a recent (>2-3 days) undiagnosed MI : Troponin

Detection of re-infarction within 1-2 weeks of the first MI : CK MB

Time interval of enzyme check: on admission , and for 2-3 times every 8-12 hours

A rise and fall pattern for CK MB is necessary

Management

TIME IS GOLD !

Reperfusion strategies

Rupture of an unstable plaque in the culprit vessel produces complete occlusion of the infarct-related coronary artery.

Dangers of coronary artery occlusion: a combination of pump failure and electrical instability

Early reperfusion shortens the duration of coronary occlusion, minimizes the degree of ultimate left ventricular dysfunction and dilation, and reduces the probability that the STEMI patient will develop pump failure or malignant ventricular tachyarrhythmias.

Golden time for myocardial salvage: 12 hours, especially first 4-6 hours

Fibrinolysis ( thrombolysis, pharmacologic reperfusion)

Angioplasty (Primary percutaneous coronary intervention, mechanical reperfusion)

Approaches

These drugs activate serum Plasminogen and convert it to active Plasmin . Plasmin then lyses the fibrin bands to fibrin degradation products. So the trombus in the infarct vassel will resolve and the blood flow restores.

Streptokinase and urokinase first generation nonspecific ( activate plasminogen in the circulation ), more bleeding side effects

Tissue plasminogen activator ( rTPA, Alteplase) second generation , specific for fibrin bound plasminogen, less bleeding

Reteplase, tenekteplase third generation, bolus administration

Fibrinolytics

Allergic reactions: Recent (<2 year) exposure to streptococci or streptokinase produces some degree of antibody-mediated allergic/anaphylactic reactions to streptokinase in most patients. Although this is of clinical consequence only rarely, it is recommended that patients not receive streptokinase for STEMI if they have been treated with a streptokinase product within the past 2 years.

Bleeding complications are, of course, most common and potentially the most serious. Most bleeding is relatively minor with all agents. Intracranial hemorrhage is the most serious complication of fibrinolytic therapy

Complications

Whenever possible, mechanical reperfusion is preferable to fibrinolysis

Normal blood flow in the infarct related artery: mechanical 90%, fibrinolysis 50%

Survival benefit Re-infarction Risk of ICH, CVA

Oxygen nasal 2-4 lit/min especially if O2 sat<90% in room air

Opiates for pain relief: Morphin sulfate 2-4 mg /10-15 min or Pethidine 25-50 mg / 10-15 min as needed

IV TNG: 5-15 micro gr/ kg/ min infusion ASA: 165- 325 mg chewing tab then daily Clopidogrel (Plavix) : 300 mg stat then 75

mg/day Heparin 1000 u/h infusion or enoxaparin 1

mg/kg SC BID Beta blockers: propranolol, metoprolol,

Atenolol in the absence of contraindications

Other drugs

Statins : Atorvastatin 80 mg stat and daily angiotensin converting enzyme inhibitors:

captopril, enalapril, lisinopril, ramipril especially in patients with pulmonary congestion or LVEF <40 percent if the following are absent: hypotension (SBP <100 mm Hg or <30 mm Hg below baseline) or known contraindications to this class of medications.

Angiotensin receptor blockers: losartan, valsartan, candesartan

Anxiolytics : oxazepam, diazepam, midazolam Stool softeners: Susp MOM, C lax Complete bed rest for 12- 24 hours then relative

bed rest unless complications present

Hospital stay: for uncomplicated MI 3-5 days and for complicated MI until the patient is fully stabilized

DISCHARGE PLANNING ASA, clopidogrel BB ACEI BP control Lipid management DM management Smoking cessation

DISCHARGE PLANNING contd Weight management Exercise program Cardiac rehab Pt education Influenza vaccine Depression screening Generally advise against HRT in women

ABCDE

A = Aspirin, ACE inhibitorB = Beta blockerC = Cholesterol lowering agentD = Don’t smoke, DietE = Exercise

Complications of MI

Cardiogenic shock is the extreme clinical expression of left ventricular failure.

It is associated with extensive damage to the left ventricular myocardium in more than 80 percent of STEMI patients in whom it occurs;

the remainder have a mechanical defect such as ventricular septal or papillary muscle rupture or predominant right ventricular infarction

This low-output state is characterized by elevated ventricular filling pressures, low cardiac output, systemic hypotension, and evidence of vital organ hypoperfusion (e.g., clouded sensorium, cool extremities, oliguria, acidosis).

Patients with cardiogenic shock caused by STEMI are more likely to be older, to have a history of a prior MI or congestive heart failure, and to have an anterior infarction at the time of development of shock.

Cardiogenic shock

loss of about 40 percent or more of the left ventricular mass.

Patients who die as a consequence of cardiogenic shock often have “piecemeal” necrosis—that is, progressive myocardial necrosis from marginal extension of their infarct into an ischemic zone bordering on the infarction.

Pathology

Vicious cycle Sustained CK MB rise Most have 3 vessel disease There is no collateral

Pathophysiology

Intraaortic balloon pump

FREE WALL RUPTURE

Rupture of the ventricular septum

Complete rupture of a necrotic papillary muscle

Ventricular tachyarrhythmias Ventricular tachycardia VT Ventricular fibrillation VF Primary: first 48 hours, caused by ischemia,

good prognosis by DC cardioversion Secondary: after 48 h, caused by aneurysm

or hemodynamic compromise, poor prognosis

Treatment: DC cardioversion, Asynchronous, 200-360 J, anti-arrhythmic drugs

ventricular tachycardia

ventricular fibrillation