Acute coronary syndromes

Patients with ischemic heart disease fall into two large groups Patients with stable angina or acute coronary syndromes patients with acute coronary syndromes (ACS) which composed of patients with acute myocardial infarction (MI) with ST-segment elevation on their presenting electrocardiogram (STEMI) and those with unstable angina (UA) and non-ST-segment elevation MI (UA/NSTEMI)

When patients with acute ischemic discomfort are first seen, the working diagnosis is that they are suffering from an acute coronarysyndrome The 12-lead (ECG) is at the center of the decision pathway for management since it permits distinction of those patients presenting with STsegment elevation from those presenting without ST-segment elevation. Serum cardiac biomarkers are obtained to distinguish unstable angina from non-STsegment MI (NSTEMI)and to assess the magnitude of an ST-segment elevation MI (STEMI).

Acute Coronary Syndrome

Ischemic Discomfort Unstable Symptoms
History Physical Exam

No ST-segment elevation

ST-segment elevation

ECG

Unstable angina

Non-Q AMI

Q-Wave AMI

Acute Reperfusion

Stable angina pectoris is characterized by chest or arm discomfort that is rarely described as pain, but that is reproducibly associated with physical exertion or stress and is relieved within 5 to 10 min by rest and/or sublingual nitroglycerin

UA is defined as angina pectoris or equivalent ischemic discomfort with at least one of three features: (1) it occurs at rest (or with minimal exertion) usually lasting 10 min (2) it is severe and of new onset (i.e., within the prior 4 to 6 weeks) (3) it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than previously) The diagnosis of NSTEMI is established if a patient with the clinical features of UA develops evidence of myocardial necrosis,as reflected in elevated cardiac biomarkers

PATHOPHYSIOLOGY UA/NSTEMI can be caused by a reduction in oxygen supply and/or by an increase in myocardial oxygen demand (e.g.,by tachycardia or severe anemia) superimposed on a coronary obstruction. Four pathophysiologic processes that may contribute to the development of UA have been identified: (1) plaque rupture or erosion with superimposed nonocclusive thrombus (2) dynamic obstruction [e.g., coronary spasm, as in Prinzmetals variant angina (3) progressive mechanical obstruction [e.g., rapidly advancing coronary atherosclerosis or restenosis following percutaneous coronary intervention (PCI) (4)secondary UA related to increased myocardial oxygen demand and/or decreased supply (e.g., anemia).

, CLINICAL PRESENTATION History and Physical Examination The clinical hallmark of UA/NSTEMI is chest pain, typically located in the substernal region or sometimes in the epigastrium, that frequently radiates to the neck, left shoulder, and left arm Look for evidence of atherosclerotic disease at other sites such as an abdominal aortic aneurysm, carotid arterial bruits, and diminished arterial pulse in the lower extremities, also look for risk factors for atherosclerosis, such as xanthelasma and xanthomas There may also be signs of anemia, thyroid disease, and nicotine stains on the fingertips from cigarette smoking. Palpation may reveal cardiac enlargement and abnormal contraction of the cardiac impulse (left ventricular akinesia or dyskinesia). Auscultation can uncover arterial bruits, a third and/or fourth heart sound, and, if acute ischemia or previous infarction has impaired papillary muscle function, an apical systolic murmur due to mitral regurgitation may be audible.

Aortic stenosis, aortic regurgitation, pulmonary hypertension (and hypertrophicCardiomyopathy (must be excluded, since these disorders may cause angina in the absence of coronary atherosclerosis. So Examination during an anginal attack is useful, since ischemia can cause transient left ventricular failure with the appearance of a third and/or fourth heart sound, a dyskinetic cardiac apex, mitral regurgitation,and even pulmonary edema If the patient has a large area of myocardial ischemia or a large NSTEMI, the physical findings can include diaphoresis, pale cool skin, sinus tachycardia, a third and/or fourth heart sound, basilar rales, and sometimes hypotension, resembling the findings of large STEMI.

Electrocardiogram In UA, ST-segment depression , transient ST-segment elevation, and/or T-wave inversion occur in 30 to 50% of patients T-wave changes are sensitive for ischemia but are less specific,unless they are new deep T-wave inversions more than or equal to 0.3 mV

 Cardiac Biomarkers Patients with UA who have elevated biomarkers of necrosis, such as CK-MB and troponin are at increased risk for death or recurrentMI. Elevated levels of these markers distinguish patients withNSTEMI from those with UA. There is a direct relationship between the degree of troponin elevation and mortality.

 DIAGNOSTIC EVALUATION factors associated with a high likelihood of ACS a clinical history typical of ischemic discomfort a history of established coronary artery disease by angiography prior MI,congestive heart failure new electrocardiographic (ECG) changes, or elevated cardiac biomarkers Factors associated with an intermediate likelihood of ACS are: age 70 years, male gender diabetes mellitus known peripheral arterial or cerebrovascular disease and old ECG abnormalities

 Diagnostic Pathways There are four major diagnostic tools used in thediagnosis of UA/NSTEMI the clinical history the ECG cardiac markers and stress testing Evaluation of such patients includes clinical monitoring for recurrent ischemic discomfort, serial ECGs, and cardiac markers, typically performed at baseline and at 4 to 6 h and 12 h after presentation. If the patient remains pain free and the markers are negative, the patient may go on to stress testing.

 standard treadmill ECG stress testing is used, but for patients with fixed abnormalities on the ECG (e.g., left bundle branch block), perfusion or echocardiographic imaging is used. For patients who cannot walk, pharmacologic stress is used. By demonstrating normal myocardial perfusion, sestamibi or thallium imaging can reduce unnecessary hospitalizations by excluding acute ischemia.

 TREATMENT Patients with UA/NSTEMI should be placed at bed rest with continuous EC monitoring for ST-segment deviation and cardiac rhythm Medical therapy involves simultaneous antiischemic treatment and antithrombotic treatment Anti-Ischemic Treatment In order to provide relief and prevention of recurrence of chest pain, initial treatment should include nitrates and beta blockers

 NITRATES Nitrates should first be given sublingually or by buccal spray (0.3 to 0.6 mg) if the patient is experiencing ischemic pain. If pain persists after three doses given 5 min apart, intravenous nitroglycerin (5 to 10 g/min) is recommended Topical or oral nitrates can be used once the pain has resolve The only absolute contraindications to the use of nitrates are hypotension or the use of sildenafil (Viagra) within the previous 24h.

 -ADRENERGIC BLOCKADE These agents are the other mainstay of antiischemic treatment. Intravenous beta blockade followed by oral beta blockade targeted to a heart rate of 50 to 60 beats/min is recommended. Heart rateslowing calcium channel blockers, e.g., verapamil or diltiazem, are recommended in patients who have persistent or recurrent symptoms after treatment with full-dose nitrates and beta blockers and in patients with contraindications to beta blockade

 Additional medical therapy includes ACE inhibitor and HMG-CoA reductase inhibitors (statins) for long-term secondary prevention If pain persists despite intravenous nitroglycerin and beta blockade, morphine sulfate, 1 to 5 mg intravenously, can be administered every 5 to 30 min as needed

 Antithrombotic Therapy This is the other main component of treatment for UA/NSTEMI Initial treatment should begin with the platelet cyclooxygenase inhibitor aspirin together with clopidogrel confer a 20% relative reduction in cardiovascular death, MI, or stroke compared with aspirin alone in both low- and highrisk patients with UA/NSTEMI

 Initial dose of asprin is 165325 mg loading dose followed by 75160 mg/d Clopidogrel Loading dose of 300 mg followed by 75 mg/d

 LONG-TERM MANAGEMENT Beta blockers are appropriate anti-ischemic therapy and may help decrease triggers for MI. Statins and ACE inhibitors are recommended for long-term plaque stabilization. Antiplatelet therapy,now recommended to be the combination of aspirin and clopidogrel for at least 9 to 12 months, with aspirin continued thereafter,prevents or reduces the severity of any thrombosis that would occur if a plaque does rupture. Thus, a multifactorial approach to long-term medical therapy is directed at preventing the various components of atherothrombosis.

STEMI
STEMI generally occurs when coronary blood flow decreases abruptlyafter a thrombotic occlusion of a coronary artery previously affected by atherosclerosis. Slowly developing, high-grade coronary artery stenoses do not usually precipitate STEMI because of the development of a rich collateral network over time. Instead, STEMI occurs when a coronary artery thrombus develops rapidly at a site of vascular injury.

This injury is produced or facilitated by factors such as cigarette smoking, hypertension, and lipid accumulation. In most cases, infarction occurs when an atherosclerotic plaque fissures, ruptures, or ulcerates and when conditions (local or systemic) favor thrombogenesis, so that a mural thrombus forms at the site of rupture and leads to coronary artery occlusion

The amount of myocardial damage caused by coronary occlusion depends on the territory supplied by the affected vessel Whether or not the vessel becomes totally occluded the duration of coronary occlusion the quantity of blood supplied by collateral vessels to the affected tissue the demand for oxygen of the myocardium whose blood supply has been suddenly limited native factors that can produce early spontaneous lysis of the occlusive thrombus the adequacy of myocardialperfusion in the infarct zone when flow is restored in the occluded epicardial coronary artery.

CLINICAL PRESENTATION
a precipitating factor appears to be present before STEMI, such as vigorous physical exercise, emotional stress, or a medical or surgical illness Pain is the most common presenting complaint in patients with STEMI. Type of pain :deep visceral Character: heavy, squeezing crushing, stabbing or burning Site : the central portion of the chest and/or the epigastrium Radiation :arms radiation ,abdomen, back, lower jaw, and neck. Associated symptoms :weakness, sweating nausea, vomiting, anxiety, and a sense of impending doom

The proportion of painless (silent ) STEMIs is greater in patients with diabetes mellitus, and it increases with age. In the elderly, STEMI may present as sudden-onset breathlessness, which may progress to pulmonary edema

 Most patients are anxious and restless altering their position Pallor associated with perspiration and coolness of the extremities Sweating

LABORATORY FINDINGS (1) ECG (2) serum cardiac biomarkers, (3) cardiac imaging, (4) nonspecific indexes of tissue necrosis and inflammation

total occlusion of an epicardial artery produces STsegment elevation. Most patients initially presenting with ST-segment elevation evolve Q waves on the ECG are ultimately diagnosed as having sustained a Q-wave MI When the obstructing thrombus is not totally occlusive, obstruction is transient, or if a rich collateral network is present, no ST-segment elevation is seen

SERUM CARDIAC BIOMARKERS

Creatine phosphokinase (CK) rises within 4 to 8 h and generally returns to normal by 48 to 72 h (non specific) More specific is CKMB Cardiac-specific troponin T (cTnT) and cardiac-specific troponin I (cTnI) Levels of cTnI and cTnT may remain elevated for 7 to 10 days after STEMI.

Myoglobin is released into the blood within only a few hours of the onset of STEMI. Although myoglobin is one of the first serum cardiac markers that rises above the normal range after STEMI, it lacks cardiac specificity, and it is rapidly excreted in the urine, so that blood levels return to the normal range within 24 h of the onset of infarction.

For the purposes of confirming the diagnosis of MI, serum cardiac markers should be measured on admission, 6 to 9 h after admission, and 12 to 24 h after admission if the diagnosis remains uncertain The nonspecific reaction to myocardial injury polymorphonuclear leukocytosis, which appears within a few hours after the onset of pain and persists for 3 to 7 days; the white blood cell count often reaches levels of 12,000 to 15,000/L. ESR is elevated gradually and remains high as long as 2 weeks