*2.1.4 Histopathology*

The most common cause of CCS is atherosclerotic coronary artery obstruction. The microscopic grading of atherosclerosis can be classified according to the Modified American Heart Association criteria [7].


**Figure 7.** *Histopathology of CCS.*

#### **Figure 8.**

*Micrographs showing the coronary tree. A, the fat tissue in the adventitia (H&E, 100X). B, the severe narrowing lumen by atherosclerotic plaque, with several hemorrhagic necrotic cores and deposition of lipids and infiltration of lipid-laden foam cells in the tunica intima and tunica media (H&E, 100X). C, Panel indicates histological findings features of fibrous cap atheroma with fibrous tissue, necrotic core, and calcification (H&E, 100X). D, intraplaque hemorrhage with the necrotic core with a form of calcification that results in irregular nodules of calcium (H&E, 100X).*

## **2.2 Non-ST elevation acute coronary syndrome**

#### *2.2.1 Abstract*

Non-ST elevation acute coronary syndrome consists of two clinical scenarios: non-ST elevation myocardial infarction (NSTEMI) and unstable angina. Clinically and in

#### *Molecular Histopathology and Cytopathology in Cardiovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.110503*

the electrocardiogram, there is no difference between them, the distinction is in NSTEMI, there is an increase in myocardial biomarkers. The treatment of NSTEMI differs fundamentally from ST-elevation myocardial infarction in approach strategy, time of intervention, and treatment modalities with or without fibrinolysis. An acute coronary syndrome is a severe event of CAD that is the leading cause of cardiovascular death and morbidity. In particular, NSTEMI still accounts for the leading proportion of acute coronary events in developed countries and worldwide. There have been many advances in the effective diagnosis and treatment of acute coronary artery syndrome. However, this is still a severe disease and needs attention [8].

#### *2.2.2 Pathophysiology*

The mechanism of ACS is due to the instability of the atherosclerotic plaque and the plaque rupture or erosion. If a large rupture and massive blood clot formation fill the entire lumen of the vessel, it will lead to a transmural myocardial infarction or STEMI. If the rupture is smaller and the clot has not yet led to a complete blockage of a coronary artery, it is unstable angina and NSTEMI. In addition, the mechanisms of the movement of small thrombosis to cause occlusion of microvascular and contraction further aggravate myocardial ischemia. The formation of blood clots occurs due to a cracked atherosclerotic plaque that reveals the subendothelial matrix, which activates the GP IIb/IIIa receptors on the platelet surface when it comes into contact with platelets, causing platelets to aggregate, thereby initiating a blood clotting cascade [9].

The consequence of the above phenomena is a serious and rapid decrease in blood flow to the myocardial area perfused by that coronary artery, clinically manifested as unstable angina pectoris, on the electrocardiogram is an image of acute myocardial ischemia with ST depression or sharp, negative T wave, elevated cardiac enzymes (troponin, CK-MB) [10–12].

## *2.2.3 Clinical diagnostic criteria*


#### **2.3 Acute ST-elevation myocardial infarction**

#### *2.3.1 Abstract*

Acute myocardial infarction (MI) is one of the leading causes of death in the US and European countries. It is estimated that in the US every year about 1 million patients are hospitalized and 200,000–300,000 deaths from acute MI. In recent years, advances in diagnosis and treatment have significantly reduced mortality from acute MI. The introduction of the coronary care unit (CCU) in the early 60s, followed by thrombolytic drugs in the 80s, and now percutaneous coronary interventions with advances in drugs therapy has reduced the mortality rate worldwide from about >30% in the past to <7% in the 2000s [15].

#### *2.3.2 Pathophysiology*

MI is caused by a complete blockage of one or more coronary artery branches causing sudden myocardial ischemia and necrosis of the myocardial area perfused by that branch of the coronary artery. The main mechanism that causes this phenomenon is the instability and rupture or erosion of the atherosclerotic plaque that causes the formation of thrombosis that fills the entire lumen of the vessels, which abruptly stops the flow of blood to nourish the myocardial area behind that and quickly leads to necrosis [9]. This necrotic process can be rapid or slow depending on whether the patient has previous collateral circulation or not [16]. More than 50% of acute MI occur on previous atherosclerotic lesions that cause only mild stenosis [17]. If the rupture causes the formation of a blood clot that is not large, and has not yet filled the entire lumen of the vessels, then the clinical manifestation is unstable angina. MI is also expanded when there is necrosis of the myocardial area associated with hypoperfusion due to other causes such as acute blood loss and severe hypotension in septic shock (**Figure 9**).

#### *2.3.3 Clinical diagnostic criteria*

The definition of myocardial infarction denotes the presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia. Diagnostic criteria for MI include an increase or decrease of myocardial biomarker (specifically cardiac troponin) and one of the following conditions:


#### **2.4 Histopathology and cytopathology of myocardial infarction**

Early in an infarct (1–3 hours), myocytes may have a wavy appearance, and there may be interstitial edema (**Figure 11A**). Increased eosinophilic staining of myocytes is *Molecular Histopathology and Cytopathology in Cardiovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.110503*

#### **Figure 10.**

*ECG anterior STEMI (left); coronary thrombus and percutaneous coronary intervention of left anterior descending (right).*

usually accompanied by contraction band necrosis and loss of myocyte nuclei (**Figure 11B**). These histologic changes can be appreciated by 4–12 hours, then infiltrated by inflammatory cells. Early ischemia, defined as the first 72 hours, is

**Figure 11.** *Histopathology of myocardial infarction.*

hallmarked by the first arrival of neutrophils as they marginate through the blood vessels and can be seen in perivascular spaces. Within the first 24–48 hours, neutrophils increase within the interstitium (**Figure 11C**); these interstitial neutrophils mainly stay intact during the first 48 hours. And within 48–72 hours, the degeneration of neutrophils begins. In other words, there is an approximately equal mix of intact and degenerating neutrophils within the first 24–72 hours of early ischemia. When it is closer to 72 hours, degenerating neutrophils and abundant cellular debris start to predominate (**Figure 11D**).

Around the third day (72 hours), there is early removal of myocytes, and the interstitial cells consist of lymphocytes, pigment-laden histiocytes, and myofibroblasts. There has been no appearance of collagen. Over the next stage of five to seven days, interstitial cells continue to proliferate. This is the most cellular stage of the healing process with a large number of interstitial inflammatory cells (**Figure 11E** and **F**). After about two to four weeks, inflammatory cells begin to decrease gradually, and collagen deposition increases (**Figure 11G**). After one to two months, only a few inflammatory cells remain, and collagen is firmly established (**Figure 11H**). After a period of two months, the inflammation ceases, and there is only a dense layer of collagen; the scar is formed. Basically, an infarct does not progress further after two months, although a well-healed scar may undergo additional changes, such as fatty infiltration and neovascularization. However, these are more variable features. There are usually remaining myocytes entrapped within areas of a healed infarct's scar, and this is a potential focus of arrhythmias (**Figure 11I** and **J**).
