Myocardial Infarction

Overview
  • Myocardial Infarctions (MIs) are a distinct manifestation of Ischemic Heart Disease characterized by ischemia of the myocardium sufficient to result in ischemic necrosis. Myocardial Ischemia is caused by sudden narrowing or occlusion of a coronary artery following fissuring or rupture of a pre-existing atherosclerotic plaque. The clinical presentation of MIs are variable and depend on the extent of coronary arterial narrowing as well as the location of ischemia. Clinically, two basic subtypes of MI are distinguished by the presence of electrophysiological changes and are thought to reflect whether the affected coronary artery has partially or completely occluded.
Pathogenesis
  • Overview
    • The most common etiology of MI is the presence of an atherosclerotic plaques within a coronary artery. MIs result from sudden rupture or fissuring of the plaque causing rapid generation of a thrombus within the coronary artery. Thrombosis can severely narrow or obstruct the coronary arteries, resulting in a mismatch between cardiac oxygen demand and blood flow that yields sufficient myocardial ischemia to cause necrosis of the tissue. As described in Ischemic Heart Disease the extent of resultant myocardial functional derangement or damage is dependent on the severity and duration of ischemia.
  • Pathogenic Subtypes
    • The pathological sequelae of MI occur along a continuum, dependent by the extent of vessel narrowing resulting from plaque thrombosis. Differences in the extent of vessel narrowing appear to affect cardiac electrophysiology differently, allowing differentiation of the extent of vessel occlusion using the ECG. Partial occlusion of coronary vasculature will not cause elevation of the ST Segment of the ECG, and is thus called a "Non-ST-Elevation Myocardial Infarction (NSTEMI)" or "Unstable Angina (UA)". Complete occlusion of cardiac vasculature results in elevation of the ECG ST Segment, and this is termed "ST-Elevation Myocardial Infarction (STEMI)". Naturally, NSTEMI/UA generally results in less pathology and milder clinical consequences than a STEMI.
Location
  • Overall Location
    • The location of infarcted tissue within the heart depends on which of the coronary arteries is occluded and what areas of cardiac tissue primarily derived their blood supply from the affected vessel. Basic anatomical themes of coronary artery supply are discussed in cardiac anatomy; however, it should be pointed out that significant individual variation exists.
  • Mural Location
    • Oxygen tension is normally lowest in the myocardium immediately deep to the endocardium (i.e. "Subendocardial Myocardium") as it is the last layer of the ventricular wall to be perfused. Furthermore, this layer also encounters the greatest pressures during ventricular systole. Consequently, infarcts typically begin in the subendocardial myocardium and spread outward given prolonged periods of myocardial ischemia. Infarctions limited to the subendocardium are termed a "Subendocardial Infarct" whereas those that grow to encompass the entire thickness of the ventricular wall are termed "Transmural infarcts".
Morphology
  • Overview
    • The morphology of a myocardial infarction evolves significantly over time and reflects processes of damage followed by healing. In general, the initial ischemic insult results in coagulative necrosis and is followed by acute inflammation of damaged tissue. Over time, the acutely inflammatory infiltrate is replaced by granulation tissue and finally is reorganized by significant fibrosis. Below we discuss the morphological changes of myocardial tissue infarcted due to a complete occlusion of blood supply
  • First 12 Hours
    • Only nuanced histological changes to the myocardium can be detected during these first few hours and thus gross examination is unhelpful. Molecular processes take place during the first few minutes of ischemia and may reach the endpoint of irreversible cell injury within 30min. Damage to endothelial cells disrupts the capillaries and results in myocardial edema beginning 4 hours after occlusion. Separation of cardiomyocyte fibers by edematous fluid manifests as "Wavy Fibers" within the myocardium. Furthermore, influx of Ca++ into damaged cardiomyocytes results in contraction of their actin-myosin fibrils that manifests as "Contraction Bands" within the cells.
  • 12 - 72 Hours
    • Grossly, the infarcted tissue is characterized by increasing pallor and is rimmed by a ring of red, hyperemia. Signs of coagulative necrosis become increasingly obvious during this entire period. Neutrophils begin to infiltrate from the lesion's borders by 18 hours. As the second day approaches, an intense acute inflammation builds and peaks by day 3.
  • 4 - 10 Days
    • During this period the lesion becomes increasingly soft and yellow. This stage is marked by replacement of neutrophils with macrophages which begin to phagocytose and degrade necrotic tissue. This process significantly compromises the myocardial structural integrity and poses the highest risk for myocardial rupture. Fibroblasts and new capillaries begin to creep into the lesion from its border, defining a zone of expanding granulation tissue.
  • 10 Days to 8 weeks
    • Phagocytosis of necrotic material by macrophages continues until all the dead tissue is resorbed and degraded. During this time granulation tissue comes to fill the entire lesion and is eventually remodeled into a firm fibrotic scar which is visible at the end of two months.
Clinical Presentation
  • Overview
    • Myocardial Infarctions present along a clinical spectrum depending on the severity of coronary artery occlusion. Today, clinicians focus on the clinical presentation, ECG changes, as well as serum biomarkers to distinguish between Stable Angina, UA/NSTEMI, and STEMI. Here we discuss the initial clinical symptomology of an acute infarction and discuss changes to the ECG and serum biomarkers in later sections. In general, the clinical features of UA/NSTEMI are milder than that of STEMI, reflecting the fact that UA/NSTEMI results from incomplete occlusion of coronary arteries whereas STEMI results from their total occlusion. Importantly, a wide variety of potentially serious complications can follow this initial presentation and these are discussed in the sections below.
  • Chest Pain
    • Chest Pain is the hallmark symptom of MI and is likely due to stimulation of nerve endings by metabolites released by cardiomyocytes undergoing ischemia. Generally, patients with MIs describe frank pain, usually localized to the substernal region, rather than chest discomfort which is more characteristic of Stable Angina. However, it is important to point out that in many cases, especially in patients with Type II diabetes, who possess some peripheral neuropathy, little to no pain may be felt. UA/NSTEMI is characterized by episodes of chest pain which lasts more than 10 minutes. These episodes may occur with increasing frequency and severity, or occur completely at rest. Chest Pain in STEMI is often more severe, prolonged, radiates to multiple regions, and is sometimes accompanied by a "sense of doom".
  • Other Symptoms
    • Other presenting symptoms of MI are largely due to defects in myocardial contraction and relaxation following ischemia. These symptoms may occur in those with Stable Angina, but are typically more severe in those with MIs, and do not resolve with rest. Additionally, these symptoms are typically more severe in those with STEMIs rather than UA/NSTEMI. Defects in ventricular contraction may lower cardiac output and thus cause reductions in systemic arterial pressure which via mechanisms Systemic Arterial Pressure - Short-term Regulation will activate the SNS, yielding tachycardia and diaphoresis. Defects in left ventricular relaxation may result in backup of blood into the lung, causing pulmonary edema and thus dyspnea. If the right ventricle is affected, then backup of blood may cause an elevation of the jugular venous pressure. Finally, a poorly-relaxing left ventricle may result in an S4 heart sound caused by atria pushing blood onto the noncompliant ventricular wall.
Clinical Complications
  • Overview
    • A wide variety of complications may result after the occurrence of an MI and yield diverse myocardial derangements that can be potentially serious and fatal. Many of these complications tend to occur at particular timescales following the MI, reflecting whether their pathogenesis derives from early post-infarctive derangements or those that require time to evolve.
  • Arrhythmias
    • In addition to affecting cardiomyocyte physical contraction and relaxation, ischemic injury can severely derange cardiomyocyte electrophysiology and thus render routes of Cardiac Action Potential - Propagation dysfunctional. A wide variety of arrhythmias may result following an MI and their development depends on the anatomic areas of cardiac tissue which become infarcted
    • However, ventricular fibrillation is of primary concern and accounts for a significant number of deaths following an MI.
  • Cardiogenic Shock
    • Cardiogenic Shock often develops when the infarcted area comprises more than 40% of the myocardium. Sadly, the severe reductions in cardiac output which follow only serve to compound myocardial ischemia.
  • Papillary Muscle Derangement
    • Functional derangement of the papillary muscle is more common that its complete rupture although this is possible. This can result in severe mitral valve regurgitation which significantly increases the functional demands on an already injured heart. Consequently, risk of death or heart failure are significantly increased.
  • Infarct Rupture
    • As described in the morphology section above, infarcts becomes increasingly soft during the second week after MI. Although infrequent, complete rupture of the infarct can occur and is more common in those with transmural infarcts. If rupture occurs on a free ventricular wall then hemopericardium and cardiac tamponade may result. If rupture occurs through the interventricular septum then a major left-right shunt results.
  • Acute Pericarditis
    • Acute Pericarditis reflects extension of post-infarctive myocardial inflammation to the pericardium. Naturally, this is more likely in those with transmural infarcts and can result in a pericardial effusion.
  • Heart Failure
    • Soon after an MI the affected ventricle begins to dilate, initially due to expansion of the infarcted tissue itself. Over time, ventricular dilation progresses likely through active remodeling of the myocardium along a pattern of eccentric ventricular hypertrophy. Such physical changes to the heart appear to be maladaptive and increase the risk of heart failure which may manifest months to years after the MI itself.
  • Ventricular Aneurysm
    • Dramatic dilations of the infarcted region weeks to months after MI can generate a true ventricular aneurysm. Aneurysms increase the risk of arrhythmias, heart failure, as well as generation of mural thrombi (see below).
  • Thrombosis
    • Dysfunction of the endocardium following MI dramatically increases the risk of thrombosis within the heart. This is especially true within the space of a ventricular aneurysm where normal blood flow may be compromised. Initially, thrombi are attached to the ventricular wall, yielding mural thrombi; however, they can easily embolize to generate systemic thromboemboli.
Laboratory Findings
  • Overview
    • Injured and dying cardiomyocytes release a variety of proteins normally sequestered in the intracellular space. Laboratory detection of these proteins is an important tool in diagnostic differentiation of MI from stable angina in which these serum biomarkers are not present. Furthermore, because these proteins are released with predictable kinetics following ischemia, their presence can help temporally localize when the infarction occurred.
  • Creatinine Kinase (CK)
    • Creatinine Kinase is an enzyme present in both cardiac and skeletal muscle; however, its MB isoform is largely specific to the myocardium. CK-MB is detectable within 3-8 hours after infarction, peaks at about 24 hours, and disappears by 2-3 days
    • It should be pointed out that total CK levels are sensitive but not specific indicators of MI as injury to skeletal muscle can also result in increased total CK. However, detection of the CK-MB subtype is more specific for MI.
  • Cardiac Troponin
    • Troponin is a protein which helps regulate excitation-ontraction coupling of muscle. The protein is present in both cardiac and skeletal muscle although specific cardiac subtypes can be specifically detected. Cardiac troponins are detectable within 3-8 hours after infarction, peak within 24hrs, but remain detectable for up to 10-14 days as their levels decline. In general, tests for cardiac troponins are more specific than those for CK-MB and are now the preferred serum biomarker for detecting MIs.
ECG Changes
  • Overview
    • Abnormalities of cardiomyocyte electrophysiological conduction are common following bouts of myocardial ischemia. These abnormalities are reflected in the ECG and are used to detect MIs and distinguish between the subtypes of UA/NSTEMI and STEMI.
  • UA/NSTEMI
    • UA/NSTEMIs result in acute depression of the ST Segment or inversion of the T wave. Importantly, elevation of the ST segment does not occur. Over time the electrophysiological abnormalities return to normal.
  • STEMI
    • STEMIs are characterized by early elevations of the ST Segment which persist for 1-2 days following infarction. In some cases, the Q wave of the QRS Complex may become enhanced several hours after MI and this may reflect the development of a transmural infarct. However, because there is several hours of lag before Q wave enhancement develops, Q waves are not frequently used for diagnostic purposes.