Myocardial infarction

MYOCARDIAL INFARCTION

• Referred to as “Heart attack” due to death of cardiac muscle due to prolonged severe ischemia

• Can occur at any age- 10% of MI occur in people younger than 40 years and 45% in younger than 65 years

• Risk increases with age as there is increased incidence of risk factors

• Males are more affected than females in middle age

• In elderly age – both are equally affected 

ETIOPATHOGENESIS OF MYOCARDIAL INFARCTION

• Etiology of IHD has been categorized into

  • Coronary atherosclerosis

  • Superadded changes in coronary atherosclerosis

  • Non-atherosclerotic causes

• Coronary atherosclerosis

  • 90% cases of IHD

  • Risk factors of atherosclerosis

  • Pathogenesis of atherosclerosis

  • Distribution

    • Can occur in one or more of the three major coronary arteries

    • Highest incidence is in anterior descending branches of left coronary

    • Next in decreasing frequency is right coronary artery and circumflex branches of left coronary artery

  • Location – area of severest involvement is about 3 to 4 cm from the coronary ostia and at or near the bifurcation of arteries

  • Morphology of atherosclerotic plaque

  • Atherosclerotic plaque may bulge into lumen causing obstruction of lumen

  • Further complications calcification, thrombosis, ulceration, hemorrhage, rupture and aneurysm formation can occur

• Superadded changes in atherosclerosis

  • Acute coronary syndromes including acute MI, unstable angina and sudden ischemic death are due to superadded changes in pre existing atherosclerotic plaque

  • These changes are

    • Acute changes in ahtheromatous plaque

    • Coronary artery thrombosis

    • Local platelet aggregation and coronary spasm

• Acute changes in atheromatous plaque –

  • hemorrhage, fissuring or ulceration resulting in thrombosis and embolization of atheromatous debris

  • These changes occur due to coronary artery spasm, tachycardia, intraplaque hemorrhage and hypercholerolemia

• Coronary artery thrombosis

  • Ulceration of fixed chronic atheromatous plaque leads to initiation of thrombosis as the lipid core of the plaque is highly thrombogenic

  •  small fragments of thrombotic material embolizes to terminal branches causing microinfarcts of myocardium

• Local platelet aggregation and coronary spasm

  • Platelet aggregates on atheromatous plaque short of forming thrombus

  • These platelet aggregates release vasospasmic mediators such as thromboxane A2 causing vasospasm of already existing atherosclerotic plaque

• Non-atherosclerotic causes

  • Vasospasm – in association with platelet aggregation and as in cocaine abuse

  • Stenosis of coronary ostia- in conditions like aortic atherosclerotic plaque encroaching on opening of coronary ostia or extension of syphilitic aortitis

  • Arteritis – as in rheumatic arteritis, poly arteritis nodosa, thromboangitis obliterans, or other bacterial infection

  • Embolism – emboli from else where in the body may occlude coronary arteries and their branches

  • Thrombotic diseases – conditions with hypercoagulability of blood such as in shock, polycythemia vera, sickle cell anemia and thrombotic thrombocytopenic purpura

  • Trauma – penetrating or blunt  injury

  • Aneurysm –

    • dissecting aneurysm of the aorta into the coronary artery may produce thrombotic coronary occlusion

    • Rarely congenital, mycotic and syphilitic aneurysms may occur in coronary arteries

  • Compression – from outside by primary or secondary tumors of the heart may result in occlusion

• Myocardial ischemia leads to decrease in oxygen supply causing cessation of aerobic metabolism. This further causes decrease in ATP, creatinine phosphate  and increase in lactic acid which reduces the contractility of myocardium

 

• Reversible changes occur with in 60 seconds

  • Myofibrillar relaxation

  • Glycogen depletion

  • Cell and mitochondrial swelling

• Irreversible changes occur if ischemia lasts for 20 to 30 minutes or more – necrosis of cardiac myocyte

• Location size and specific morphologic features of acute MI depends upon

  • Location, severity and rate of development of coronary obstruction

  • Size of vascular bed perfused by obstructed vessel

  • Duration of occlusion

  • Metabolic or oxygen needs of myocardium at risk

  • Extent of collateral blood vessels

  • Other factors such as cardiac rate, blood oxygenation etc

• Common Location of infarcts

  • Most commonly located in left ventricle

  • Atrial infarcts are more common in right atrium. Left atrium is protected due to the supply of oxygenated blood to left atrium

  • Region of infarction depends upon the obstructed coronary artery

    • Stenosis of anterior descending artery –Most common (40-50%). Region infarcted – apex and anterior 2/3rd of interventricular septum

    • Stenosis of right coronary artery – Next in frequency (30 -40%). Region infarcted – posterior part of left ventricel and posterior 1/3rd of interventricuular septum

    • Stenosis of left circumflex coronary artery – Less frequent (15-20%). Region infarcted – lateral wall of left venrticle

• Patterns of infarction

  • Transmural – Necrosis involves full thickness of cardiac wall

  • Subendocardial – Necrosis involves the least perfused area à subendocardial region – inner 1/3rd of ventricular wall (caused by plaque disruption followed by coronary thrombus or in shock)

  • Multifocal microinfarction – occurs when smaller intramural vessels are involved ß microembolization, vasculitis, vasospasm

Morphological changes in myocardial infarction

• Development of Gross and Microscopic features depends on the survival of the patients post MI

• Gross changes are not apparent until 4 hrs.

• Microscopic changes are not significant until 4 hrs

• If infarct has occurred 2 to 3 hrs before death, areas of infarction can be highlighted by  immersing tissue slices in solution of Triphenyl tetrazolium chloride. This stain imparts brick red colour to intact, non-infarcted myocardium where lactate dehydrogenase is preserved whereas in the infracted area, this enzyme leaks out of the cells due to disruption of the membrane

• Gross and microscopic changes in myocardial infarction are

• Clinical features 

  • Rapid, weak pulse and profuse sweating

  • Chest pain- Crushing, stabing, squeezing pain

  • Nausea & vomiting

  • Left upper arm pain

  • Dyspnoea  due to impaired contractility of ischemic myocardium with resultant pulmonary congestion and edema

  • 10% – 15% – asymptomatic

• 
  

  Biochemical markers for myocardial infarction 

  • Diagnosis is based on blood levels of proteins that are leaked out from irreversibly damaged myocyte

  • These molecules include –

  • • Cardiac specific troponins T and I (cTnT & cTnI)

  • • MB fraction of creatine kinase (CK-MB)

    • Lactate Dehydrogenase (LDH)

    • Myoglobin

  • Cardiac-specific troponins (cTn)

    • Most sensitive & specific biomarkers of MI

    • Troponins – regulate calcium mediated contraction of cardiac and skeletal muscle

    • They are Cardiac troponin T (cTnT) & Cardiac troponin I (cTnI)

    • Not found in the blood normally

    • Post MI – begin to rise at 3-12 hours

    • cTnT levels peak – 12-48 hours

    • cTnI levels peak –  24 hours

  • Creatine kinase

    • Enzyme present in brain, myocardium and skeletal muscle

    • It is a dimer composed of two isoforms designated as “M” and “B”.

    • MM homodimer – present in cardiac muscle and skeletal muscle

    • BB homodimer –present in brain, lung and many other tisuues

    • MB heterodimer – present in cardiac muscle (lesser amount in skeletal muscle)

    • MB form of  Creatine kinase is sensitive but not specifc

    • Rises within 3-12 hrs of onset of MI,

    • Peaks in approximately  24 hrs

    • Returns to normal by 72 hrs

  • But elevated Troponin levels persists for approximately 10 to 14 days after acute MI

  • Lactate dehydrogenase (LDH)

    • Lacks sensitivity

    • Enzyme is present in various tissues – myocardium, skeletal muscle, kidneys, liver, lungs and red blood cells

    • It has 2 forms LDH 1 & 2.

    • LDH 1 – more myocardial specific

    • LDH1:LDH2 > 1  — Indicates MI

    • LDH peaks in 3 days and persists for 4 to 7 days

  • Myoglobin

    • First marker to be elevated after MI

    • Lacks cardiac specificity

    • Excreted rapidly in urine

    • Its level return to normal within 24 hrs post acute MI

  SUMMARY OF MARKERS OF MI

  

• ECG – Electrocardiography

  • ST segment elevation

  • T wave inversion

  • Appearance of wide deep Q waves

• COMPLICATIONS

  • Arrhythmias

  • Congestive heart failure

  • Cardiogenic shock

  • Mural thrombosis & thromboemboli

  • Rupture

  • Cardiac aneurysm

  • Pericarditis

References

1. Vinay kumar, Abul K.Abbas, Nelson Fausto, Jon C. Aster. Robbins and Cotran Pathologic basis of disease. 8th edition.

2. Harsh mohan. Text book of Pathology.8th edition.2019