Thrombosis of a ruptured or eroded atherosclerotic plaque is the usual underlying precipitating factor for acute coronary syndrome.
Approximately 64% ACS are due to rupture of lipid laden plaque that is incited by inflammation and followed by platelet rich thrombosis.
Other causes of ACS include plaque erosion, calcific nodules, coronary spasm, spontaneous coronary artery dissection, coronary embolism, and myocardial infarction with nonobstructive coronary arteries.
When thrombus completely occludes the blood vessel STEMI occurs and when it is nonocclusive NSTEMI typically occurs.
Approximately 5% of patients with ACS die before hospital discharge.
Atherosclerotic plaques are the pathologic substrate for the development of ACS.
Coronary atherosclerotic plaque rupture with thrombus formation accounts for approximately 70% of fatal acute MRIs and sudden coronary deaths.7
Accounts for most coronary heart disease related hospitalizations in American adults, with about 2.2 million hospitalizations annually.
STEMI accounts for approximately 30% of ACS and nonSTEMI accounts for approximately 70% of ACS cases.
More than 60% of hospital admissions for ACS involve patients over the age of 65 years.
The most common symptom of ACS is chest discomfort, 79%, in men in 74% in women.
Other comment symptoms besides chest discomfort includes dyspnea, pain between the shoulder blades, neck pain, palpitations, joint pain, nausea and vomiting, fatigue, indigestion, dizziness, syncope, stomach or epigastric pain, left arm and shoulder pain, and diaphoresis.
Risk factors include: older age, current tobacco use, diabetes, elevated lipids, blood pressure and body mass index.
High income countries have experienced a decline in MI since approximately the mid-1980s, probably associated with smoking cessation.
More than two thirds of events arise from disruption of the protective fibrous cap overlying a large lipid core, exposing the underlying thrombogenic contents of the necrotic core to the bloodstream.
Describes abrupt reduction of blood flow to myocardial tissue and is typically associated with rupture of a coronary athersclerotic plaque.
Plaque rupture exposes the blood to contents of the plaque resulting in deposition and activation of platelets and formation of thrombi.
Plaque rupture activates to pathways: first, exposure of subendothelial matrix and vasoactive factors leads to thromboxane A2 and adenosine diphosphate generation and activation of P2Y12 and protease activated receptors.
Via autocrine and paracrine mechanisms, activation of glycoprotein IIb/IIIa receptors lead to platelet aggregation.
A second mechanism of exposure of tissue factor lead to activation of factors VII and X.
Minor thrombin generation results and perpetuation of coagulation process on the surface of platelets where a large amount of thrombus is formed.
With complete thrombotic occlusion ST segment elevation myocardial infarction occurs, whereas in acute coronary syndromes incomplete impairment of bloodflow in the coronary arteries resulting in unstable angina or, when biomarkers for myocardial injury are present, non–ST-segment elevation myocardial infarction ensues.
This risk stratification drives most treatment decisions during hospitalization and is important for prognosis in treatment recommendations after discharge.
Separate practice guidelines exist for the two clinical conditions-this subdivision is important pathophysiologic and, more importantly, therapeutic applications because immediately put reperfusion therapy as recommended for STEMI, whereas NSTE ACS mandated to early risk stratification in a more graded invasive approach.
Among the most common cardiac emergencies.
STEMI implies a completely occluded coronary artery
Patients may present with substernal chest pain, left upper extremity pain, mandibular pain, or epigastric discomfort or an ischemic equivalent such as dyspnea.
The coronary syndrome generally occurs after the fourth decade of life unless the patient has an inheritable condition, radiation exposure, coronary vasospasm, inflammation, or recent cocaine use.
Guidelines suggest an early strategy for high-risk patients with non-ST elevation acute coronary syndrome.
When ACS is suspected performing an electrocardiogram within 10 minutes of presentation is indicated.
If ST segment elevation is present emergency coronary angiography should be performed within two hours to confirm the diagnosis of STEMI and treat with percutaneous intervention.
STEMI should be treated with immediate coronary catheterization and coronary angiography followed by PCI with drug eluting stent implantation: rapid reperfusion with primary PCI within 120 minutes reduces mortality by 2% from 9 to 7% compared with fibrinolytic therapy.
if PCI is not performed within approximately 120 minutes of presentation of STEMI, fibrinolytic therapy should be administered in full dose with people younger than 75 years and half dose for patients 75 years or older; if there are no contraindications.
An early invasive strategy is associated with lower in-hospital mortality in women with non-ST elevation acute coronary syndrome.
Less than 10% of patients with ACS have unstable angina.
STEMI comprises approximately 25% of ACS patients.
In high-income countries patients with non -ST-elevation ACS are passing those presenting with ST-elevation MI and with increasing levels of mortality and morbidity.
Among elderly patients with ST elevation myocardial infarction treated by percutaneous coronary
intervention still have twice the risk of a one year mortality and stroke compared with non-ST elevation acute coronary syndrome patients.
There may be sex differences in ACS presentation with absence of pain or discomfort as a symptom more common in women than men (37% vs 27%).
Risk of recurrent ischemic complications remains high despite early revascularization procedures and the dual antiplatelet therapy.
Patients with previous acute coronary syndrome (ACS), adding alirocumab to high-intensity statin therapy was associated with a reduction in the risk of recurrent ischemic cardiovascular events.
Estimated 2 million hospitalizations per year in the U.S.
Approximately 1.3 6 million hospitalizations each year, of which 0.8 1 million are for myocardial infarctions and the remainder for unstable angina.
Approximately 1,350,000 people have ACS with or without ST segment elevation annually.
Approximately 3-10% of patients are 45 years or younger.
Patients with precocious acute coronary syndrome tend to be obese, have a high prevalence of smoking and hyperlipidemia.
Unrecognized renal insufficiency is a common process with acute coronary syndrome, affecting almost 1/5 of patients.
Young patients with acute coronary syndrome frequently have a thrombus in the absence of underlying coronary disease, suggesting thromboembolic events or a de novo thrombotic occlusion and it may reflect a primary hemostatic dysfunction in a number of these patients ( Davidson L et al).
Risk factors for acute coronary syndrome include poor diet, smoking, physical inactivity, high body mass index, alcohol consumption, large waist circumference, hypertension, hyperlipidemia, diabetes mellitus, and family history of cardiovascular disease.
NSTE- acute coronary syndrome is the most common manifestation of acute ischemic disease in the very elderly, with advanced age with higher risks of mortality, recurrent ischemia, and readmission to hospital.
Guidelines for the assessment of chest pain suggest that if the initial ECG is not diagnostic, but there is suspicion for acute coronary syndrome, serial ECGs at 15-30 minute intervals should be done to detect the development of ST-segment elevation or depression.
Approximately 2/3 of patients with myocardial infarction have non-ST elevation MI and the rest have ST elevation MI.
For patients with NSTE-ACS if the troponin measurements are increased above the 99th percentile, the initial therapeutic options consist of a conservative or invasive approach with coronary angiography followed by revascularization, depending on the coronary angiogram results.
Typically percutaneous treatment with drug eluting stents is used for patients with a NSTE-ACS, with coronary artery bypass grafting reserved for complex multivessel disease in patients at low risk for surgical complications, such as perioperative stroke or prolonged surgery recovery.
Patients with previous stroke, multiple comorbidities, or frailty are a Tx particular risk for surgical complications.
TIMI and GRACE risk scores predict the risk of mortality and repeated ACS and the used guide therapeutic decisions.
Because rupture of a plaque causes platelet activation and thrombosis treatment for unstable angina and non–STEMI is treated by inhibiting platelet function and by inhibiting the coagulation cascade.
After an acute coronary artery disease event patients experience a high rate of serious complications including death, myocardial infarction and progressively recurring unstable angina requiring intervention.
Patients with high risk for ischemic complications during unstable angina/non-ST-segment elevation myocardial infarction include age greater than 75 years, anginal symptoms of greater than 20 minutes duration, acceleration of angina symptoms during the preceding 48 hours, findings of congestive heart failure, the presence of mitral regurgitation murmur, tachycardia, bradycardia, hypotension, the presence of transient ST-segment deviation of greater than 0.5 mm with angina at rest, the presence of a new bundle branch block on EKG, elevated cardiac biomarkers,and sustained ventricular tachycardia (Anderson JL).
Incidence of serious complications declines after 1 month, and then gradually diminishes so that after about 6 months, the incidence of coronary death and myocardial infarction is fairly constant for the next several years, reflecting a stabilization of the clinical coronary disease.
Recurrent ischemic events after PCI can be due recurrence at original treatment site, presence of untreated lesions, or progression in lesions.
Plaques with a high risk of disruption called vulnerable plaques.
Plaque stability varies with high risk or vulnerable plaques those with a large lipid core, thin fibrous caps, high density of macrophages and T lymphocytes, with a relative paucity of smooth muscle cells, increased expression of matrix metalloproteinases, outward remodeling, increased neovascularization and intraplaque hemorrhage.
Plaque rupture exposes thrombogenic sub endothelial components that lead to platelet deposition and activation.
Most retrospective studies show that atherosclerotic plaques responsible for ACS are angiographically mild (Ambrose JA et al, Glaser R et al)
Platelets that are activated express glycoprotein IIb/IIIa receptors to bind fibrin strands and stimulate platelet cross-linking.
Activated platelets release, local mediators, promoting further platelet accumulation, activation, vasoconstriction, thrombosis, and mitogenesis.
Two types of thrombi form after plaque rupture: a platelet rich clot (white clot) that forms in areas of high stress and only partly occludes the artery, or a fibrin rich clot (red clot) the result of an activated coagulation cascade and decreased flow in the artery.
Red clots are frequently superimposed on white clot and results in complete occlusion of the vessel.
Only white clots are found in unstable angina and non-STEMI, and STEMI associated with red clots (Sherman CT, DeWood MA).
Thrombotic coronary occlusion after rupture of a lipid-rich atheromatous plaque with only a thin layer of intima covering the thin cap fibroatheroma is the most common cause of MI and death from cardiac causes
Non critical stenosis (less than 50%) may be associated with abrupt progression to severe or total occlusion and account for as many as two-thirds of cases of ACS.
In patients with acute coronary syndromes the use of aspirin and statins are associated with a lower risk of presenting with ST-segment elevation as a marker of larger infarctions (Spencer FA).
At least 80% of patients with ACS have multiple plaque ruptures distinct from the offending lesion (Rioufol G).
Anti-thrombotic drugs target the various pathways to lower the ischemic risks from prothrombotic state in patients presenting with ACS.
Autopsy studies have shown plaque rupture causes 75% of fatal myocardial infarctions, and superficial erosions accounts for the remaining 25%(Davies MJ).
Platelet thrombi can embolize distally and plug the microcirculation, which is associated with poor outcome.
Atherosclerotic plaques have heterogeneity, even among an individual.
Inflammation with macrophages increases the vulnerability of plaques by enlarging the lipid core, thins the plaque and increases risk of rupture.
CRP elevation correlates with number of plaque ruptures and may indicate the level of activity of macrophages.
Most patients have a series of vascular changes associated with coronary atherosclerosis resulting in the formation of one or more vulnerable plaques.
Non critical stenosis (less than 50%) may be associated with abrupt progression to severe or total occlusion and may account for as many as two-thirds of cases (Chen L).
Vulnerable plaques usually have high lipid content and macrophage content leading to mild to moderate luminal narrowing.
Each additional 100 g serving of fish per week is associated with a 5% reduce risk of acute coronary syndrome.
Plaque formation, primarily involves the intima of large medium sized arteries, which progresses throughout a person’s lifetime until manifesting as an acute ischemic event.
With endothelium damage monocytes, and other inflammatory cells, migrate to the subendothelium and bind to endothelial adhesion molecules and differentiate to become macrophages.
Macrophages digest oxidized LDL that also penetrate the arterial wall forming foam cells and formation of fatty streaks.
Activation of macrophages at the site release chemo attractants and cytokines that result in recruitment of additional macrophages
and vascular smooth muscle cells at the site of the plaque.
Cytokines at the plaque site include monocytic chemo attractant protein 1, tumor necrosis factor alpha, and interleukins.
Vascular smooth muscle cells can synthesize extracellular matrix at the site of plaque.
Macrophages at the site of the plaque secrete matrix metalloproteinases which are enzymes that can digest extracellular matrix and lead to disruption of the plaque.
The smooth muscle to macrophage ration increases plaque vulnerability to rupture.
Rupture of the plaque can lead to this syndrome, but in 90% of cases it remains silent when it occurs.
Atherosclerosis lesion progression is variable, nonlinear and unpredictable (Virmani R).
In a prospective studt of patients with ACS undergoing 3 vessel coronary angiography and gray-scale and radiofrequency intravascular ultrasound after PCI: major adverse cardiovascular events occurred with follow-up with equal recurrence at the site of culprit lesions as to nonculprit lesions (Stone GW et al).
Coronary risk factors, including hypercholesterolemia, hypertension, diabetes and smoking influence the process.
Hyperglycemia is predictor of survival in patients with acute coronary syndromes.
Statins should be initiated at the time of presentation and all patients with ACS.
Risk factors result in endothelial dysfunction and play a pivotal role in the initiation of atherosclerosis.
Dysfunctional endothelium has reduced bio availability of nitric oxide and has excessive production of endothelin-1, which impairs vascular hemostasis, increases adhesion molecules and increases thrombogenicity of blood via the secretion of locally active substances.
B-blockers treatment of choice for unstable angina, ST-segment elevation and non-Q-wave myocardial infarction.
ST elevation indicates that the culprit artery is completely occluded and that the patient will most likely develop a ST elevation myocardial infarction.
Absence of ST elevation in patients with unstable angina and non-Q wave myocardial infarction indicates that the culprit artery is only partially or intermittently occluded or that a rich collateral circulation exists.
With non-ST elevation is diagnosed in a patient with acute ischemic symptoms and new EKG findings with ST-depression or T-wave inversion, or both, and such patients may have an elevation in cardiac enzymes.
Patients with non-ST elevation are recommended to have early evaluation with coronary artery catheterization.
Patients with non ST elevation and cardiac enzyme elevations are considered to have had an myocardial infarction while those without such enzymes have unstable angina.
Unstable angina, and non ST-elevation myocardial infarction are closely related processes with similar pathophysiology, and clinical presentation, but differed in their severity.
If biomarkers cannot be detected, hours after the initial onset of ischemic chest pain a patient is considered to have unstable angina.
Diagnosis of non-ST-elevation myocardial infarction can be made when the ischemia is sufficient to cause elevation of cardiac biomarkers such as troponins and creatine kinase.
Frequency of women presenting with ACSs has declined, with less ST-elevation myocardial infarction and comorbidities.
In aspirin treated patients without ST elevation the use of short-term unfractionated heparin or low molecular heparin halves the risk of myocardial infarction or death.
Unfractionated heparin, particularly when combined with a glycoprotein IIb/IIIa receptor inhibitor at the time of PCI is effective and widely used.
Previously no convincing difference in efficacy or safety between low molecular heparin and unfractionated heparin, although recent systematic overview suggested enoxaparin is more effective than unfractionated heparin.
Nonocclusive intracoronary thrombi are present in 85% or more of patients with non-ST segment elevation suggesting that vascular occlusion that leads to myocardial infarction or sudden death results from repeated plaque fissures and mural thrombosis.
Dual antiplatelet therapy with adenosine diphosphate receptor antagonist and aspirin is the standard treatment for patients with acute coronary syndromes.
The third-generation prasurgrel and ticagrelor provide greater and more rapid and more consistent inhibition than their predecessor clopidogrel.
The third-generation Antiplatelet agents have a faster onset of action and more predictable and more potent platelet inhibition, with a fewer drug-drug interactions.
Among patients with acute coronary syndromes with or without ST-segment elevation the incidence of death, myocardial infarction, stroke was significantly lower among those who received prasurgrel than among those who receive ticagrelor. (ISAR-REACT 5 trial).
Prasurgrel is recommended mainly when a percutaneous coronary intervention is planned in patients who are not considered to be at high risk for bleeding (TRITON-TIMI trial).
Vorapaxar use in acute coronary syndromes without ST-segment elevation and 82 standard dual antiplatelet therapy resulted in fewer myocardial infarctions (Becker RC etbal, Goto S et al).
In a multinational, double-blind, randomized trial comparing vorapaxar with placebo in 12,944 patients with acute coronary syndrome without ST-segment elevation: the addition of this agent to standard therapy did not reduce endpoints of myocardial infarction, stroke, recurrent ischemia, or urgent coronary revascularization, but did significantly increased the risk of major bleeding, including intracranial hemorrhage (Investigators in the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER).
In a double-blind, randomized trial, of 7243 patients under the age of 75 years receiving aspirin, with unstable angina or myocardial infarction without a ST segment elevation who did not undergo revascularization were treated with prasugrel10 mg daily versus clopidogrel 75 mg a day: pasugrel did not significantly reduce the frequency of the primary endpoint, as compared with Clopidogrel and similar risks of bleeding were observed (Roe MT et al).
Early strategy of angiography with triage to either percutaneous coronary intervention, coronary artery bypass or medical management results in reduced myocardial infarctions and deaths compared to those with conservative care.
Coronary CT angiography has a very high negative predictive value for the detection of coronary disease.
In a study of 1370 subjects with low to intermediate risk patients presenting with possible acute coronary syndromes a coronary CT angiography strategy was a safe process for the expedited discharge from the emergency department of many patients who would otherwise be admitted (Litt H et al).
Upstream use of platelet glycoprotein IIb/IIIa inhibitors prior to angiography reduces myocardial infarction and death rate at 30 days, at the expense of bleeding complications.
In patients with myocardial infarction and ST elevation, in which the infarcted artery is usually occluded an ongoing process of ischemia is present.
Because of the differences in the pathophysiology of unstable angina/NSTEMI compared to STEMI different therapeutic goals and treatment approaches are required.
In unstable angina/NSTEMI antithrombotic therapy is utilized to prevent further thrombosis, to allow endogenous fibrinolysis to dissolve the clot and to reduce the degree of coronary artery stenosis, while revascularization is used to increase blood flow and prevent reocclusion or recurrent ischemia.
Cornerstone of management is coronary revascularization in candidates with suitable anatomy.
In patients with STEMI immediate revascularization should be sought with either a percutaneous approach or fibrinolysis.
Antiplatelet and anticoagulant therapy support reperfusion where intracoronary plaque rupture or erosiion and thrombosis are the underlying mechanisms.
In patients with high risk for future events early invasive strategy of cardiac catheterization and revascularization is recommended and in most cases Intracoronary stents are implanted to treat the plaque rupture.
Because stents can produce further plaque trauma, and platelet dependent thrombosis, and embolization into the coronary microcirculation patients are treated with platelet inhibitors to prevent recurrent ischemia after percutaneous coronary intervention.
Guidelines recommend dual antiplatelet the therapy with aspirin plus another agent in patients with non-STEMI undergoing PCI.
In STEMI the artery is completely occluded and reperfusion with drugs or a catheter based reperfusion is the initial approach.
Symptoms of unstable angina/NSTEMI and STEMI are similar and require an EKG for differentiation.
The earlier primary percutaneous coronary intervention (PC I) can be performed, the lower the mortality.
Strategies of PCI and antiplatelet therapy have resulted in reduced short and long-term mortality and morbidity the among acute coronary syndrome patients.
Percutaneous coronary intervention is the mainstay of revascularization a moderate to high-risk patients with non-ST elevation acute coronary syndrome and undergoing an early invasive strategy.
In patients with acute coronary syndromes without ST segment elevations including unstable angina and myocardial infarction the involved artery is often patent , and there is usually no ongoing transmural ischemia and the patient often has a good response to medical management.
Stable angina is typically described as deep, poorly localized chest or on discomfort that is exacerbated by physical activity or emotional distress and relieved by rest, nitroglycerin, or both, while unstable angina is more severe, occurs at rest and usually best described as pain.
Acute coronary syndrome pain is located in the substernal region, with radiation of the pain or pressure to the neck, jaw, left shoulder and left arm.
Some patients present with discomfort other than chest pain, and may have dyspnea, nausea, vomiting, diaphoresis and unexplained fatigue, described as anginal equivalent.
Rarely ACS may present as syncope.
Sharp, stabbing or pleuritic pain, or pain reproducible by palpation or movement, or localized with the tip of a finger are usually not ischemic. The
In a randomized study of 3031 patients with acute coronary syndromes without ST elevation undergoing early intervention that is coronary angiography, less than 24 hours after randomization or delayed intervention with coronary angiography more than 36 hours after randomization; early intervention did not differ greatly from delayed intervention in preventing the primary outcome of death, myocardial infarction, or stroke at. six months (MEHTA): but it did reduce rate of composite secondary outcomes of death, myocardial infarction or refractory ischemia and was superior to delayed intervention in high risk patients.
While glycoprotein IIb/IIIa inhibitors are indicated with acute coronary artery syndromes who are undergoing an invasive procedure the optimal timing of initiating such therapy is unknown.
The American College of cardiology and the American Heart Association recommend that patients with high-risk features receive aspirin, and clopidogrel or a glycoprotein IIb/IIIA inhibitor before angiography.
In a study of 9492 patients with ST elevation assigned to eptifibatide 12 hours or more before angiography found its use increased risk of bleeding and need for blood transfusion (Guigliano).
Clopidogrel beneficial in patients without ST-segment elevation.
Aspirin given for greater than 30 days reduces secondary vascular events by 25-30% after acute coronary syndromes, but the rate of death and myocardial infarction remains high.
CURE trial 12,562 patients adding clopidogrel to aspirin decreased combined incidence of cardiovascular deaths, myocardial infarction, and strokes from 11.4 to 9.3 percent.
Adding clopidogrel to aspirin increases severe bleeding from 2.7 to 3.7% in the management of this process.
Proton pump inhibitors often utilized prophylactically with clopidogrel to reduce gastrointestinal bleeding risk.
Clopidogrel-protein pump inhibitors (PPIs) may decrease effects of clopidogrel on platelet aggregation inhibition.
Clopidogrel-protein pump inhibitors (PPIs)-when utilized with clopidogrel after hospital discharge for acute coronary artery syndrome associated with increased risk of adverse outcomes compared to the use of clopidogrel alone.
Death or myocardial infarction occurs in 9-11% of patients with non-ST segment elevations within 4-6 weeks after the onset of symptoms.
Heparin mainstay of treatment for these syndromes.
Only low-molecular weight heparin-enoxaprin, has been shown to reduce the risk of coronary events in patients with non-ST segment elevation acute coronary ischemia.
Stroke uncommon (1.3%) associated event but stroke increases 6-month mortality by four-fold.
Patients more likely to carry PlA2 variant of the GP IIIa receptor than controls.
Enoxaprin is comparable to unfractionated heparin in the treatment of high-risk patients with non-ST-segment elevation acute coronary syndrome.
Bleeding during anticoagulant and anti-platelet therapy associated with increased risk of death, myocardial infarction and stroke.
Invasive strategies involving coronary angiography and revascularization results in reduced incidence of myocardial infarction, severe angina and rehospitalization over a follow-up of 17 months.
Aspirin, clopidogrel and an antithrombotic agent, either unfractionated heparin or low molecular weight heparin are also recommended for patients in whom an invasive strategy is chosen.
Routine invasive strategies associated with a higher early mortality rate.
Serial measurements of BNP after presentation predicts risk of death or new CHF.
In unstable angina coronary artery bypass graft surgery does not improve rates of myocardial infarction or death compared to medical treatment alone, but does improve, temporarily, the frequency and severity of anginal episodes.
5% of patients with atypical syndrome present with abdominal pains.
The rate of ischemia and bleeding complications in ACS is related to the type and intensity of the anti-thrombotic and anticoagulation therapy.
Bleeding complications in the treatment of ACS is associated with increased mortality and may directly or indirectly increase rates of myocardial infarction and stent thrombosis, and bleeding and avoidance strategies are associated with improved survival.
Following an ACS event patient should have lifestyle modification, plant-based dieting, daily exercise, a cardiac rehabilitation program, smoking cessation and antithrombotic , and lipid lowering medication.
Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is indicated for at least one year after event.