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Coronary artery disease: Stable-unstable angina and myocardial infarction - Cases of coronary artery disease.

Coronary artery disease: Stable-unstable angina and myocardial infarction - Cases of coronary artery disease. 


IMPORTANT NOTE : THE SITE IS UNDER DEVELOPMENT AND CONTENTS ARE CONTINUOUSLY ADDED.

VIDEO: A case of coronary artery disease: ECG, echocardiogram, coronary angiography and treatment.





NOTES


Coronary artery disease

DEFINITION
Coronary artery disease (CAD) is a disease characterized by limitation of coronary blood flow to the myocardium as a result of atherosclerotic lesions. It usually manifests with exertional symptoms (such as stable angina) but also by non-exertional manifestations such as an acute coronary syndrome (unstable angina, Non-ST elevation myocardial infarction, ST- elevation myocardial infarction), arrhythmias and sudden cardiac death.

Risk factors for coronary artery disease 

These are factors that are linked to an increased probability of a person to have coronary artery disease: Age, male sex, hypertension, hyperlipidemia, diabetes mellitus, tobacco use, family history, obesity, peripheral vascular disease. Cigarette smoking is probably the most important of the modifiable cardiovascular risk factors. In smokers, the incidence of CAD is about 3 times higher than in nonsmokers.

Causes and manifestations of myocardial ischemia and coronary artery disease (CAD)

Myocardial ischemia is a condition caused by the impairment of coronary blood flow, or by a coronary blood flow which is not adequate to fulfill the needs of the myocardium, either because of a decreased coronary blood flow, or because of an increased myocardial oxygen demand.
The most common cause of myocardial ischemia is atherosclerotic coronary artery disease (CAD), which decreases coronary blood flow, but there are also other causes, for example coronary arterial spasm, coronary arterial embolism, congenital anomalies of the coronary arteries, and also conditions causing an increased myocardial oxygen demand, such as myocardial hypertrophy (due to hypertension, aortic stenosis, or cardiomyopathy), severe aortic regurgitation, etc.
Manifestations of myocardial ischemia are the following: 

Stable angina, acute coronary syndromes (acute myocardial infarction or unstable angina), arrhythmias and sudden cardiac death.
The pain or discomfort, that commonly occurs in myocardial ischemia has the following characteristics:
Central (retrosternal) or left anterior chest discomfort, which is rather diffuse and not sharply localized, often described as squeezing, choking, heavy, and occasionally burning sensation. Discomfort is usually located in the retrosternal (central chest) area with possible radiation to the neck, shoulders, arms, jaw, epigastrium, or back. In some instances, it is located in these areas of radiation without affecting the retrosternal region. This description of the location of the ischemic discomfort holds true not only for stable angina, but also for unstable angina or acute myocardial infarction.
Angina typically lasts 3 to 5 minutes and usually does not last more than 20 minutes.The pain of acute myocardial infarction usually lasts more than 20-30 minutes and is often more severe than the pain of angina. 
Women and diabetics often may not present with the classic symptoms, but they may have dyspnea as the main manifestation. 
The pain of angina is elicited by physical exertion (this is the most usual and characteristic precipitating condition), emotional stress, cold exposure, smoking, sometimes even with light physical activity after consumption of a heavy meal.
Associated symptoms can include fatigue, dyspnea, weakness, nausea, diaphoresis (sweating), lightheadedness, altered mental status, and syncope.
The transition from stable coronary artery disease to unstable angina must be carefully monitored. Symptoms of concern include
more frequent episodes of chest pain, chest pain that occurs at a lower level of exercise than before, has a larger duration, or is less responsive to nitroglycerin than before, or a first episode of chest pain, with characteristics suggestive of myocardial ischemia, in a person with a high or intermediate pretest probability for CAD.
A person's pretest probability for CAD is estimated according to age, sex, risk factors and typical or atypical characteristics of symptoms.


Diagnostic tests for patients with suspected or known coronary artery disease

These diagnostic studies are useful to establish the diagnosis, to determine the prognosis and to guide treatment decisions. 
The Electrocardiogram (ECG) is useful in the assessment of chest pain and helps to stratify patients who are at risk for an adverse event. The baseline ECG of a person with chronic CAD can often be normal (in about 50% of the cases). The resting, baseline ECG in some patients with chronic CAD, or stable angina shows focal abnormal findings of ST segment depression or T wave inversions (negative T waves in leads with a positive net QRS, where a positive T wave, would be expected, see chapter The Electrocardiogram). In such cases, ECG findings, although not entirely specific, can raise suspicion of CAD, especially in individuals with risk factors. However, many people with chronic ischemic heart disease, have a normal tracing at rest (even patients with extensive coronary artery disease). Moreover, in addition to myocardial ischemia, other conditions can also produce ST-T wave abnormalities, such as left ventricular hypertrophy or dilation due to long-standing hypertension, or due to valvular heart disease, cardiomyopathies (especially hypertrophic cardiomyopathy), neurogenic effects, electrolyte abnormalities and antiarrhythmic drugs. An important diagnostic finding is a relatively recent change in the ECG in comparison to a previous one, with new ST-T wave abnormalities on the resting ECG. This finding leads to serious suspicion of CAD and often also correlates with the severity of the disease.
 The presence of pathologic Q waves indicating a previous myocardial infarction, or the presence of persistent ST depression is associated with worse prognosis (higher probability for an unfavorable outcome). 
In patients with chronic CAD, the ECG often may reveal various
conduction disturbances, most frequently left bundle branch block (LBBB) or left anterior fascicular block. Such findings can raise a suspicion of underlying CAD, especially in people with risk factors, but they are not specific for CAD. They can also occur in patients with another underlying cardiac disorder and in some cases they are idiopathic (occurring in people without any detectable underlying cardiac disorder). Arrhythmias, especially ventricular premature
beats, are relatively frequent findings in the ECG of CAD patients, but they are not diagnostic for CAD since they have a low sensitivity and specificity for coronary artery disease.
An Electrocardiogram (ECG) is also important for the diagnosis of an acute coronary syndrome (ACS). If the ECG is recorded during cardiac ischemic pain, it usually shows abnormalities such as horizontal or downsloping ST segment depression, or negative T waves 1 mm (0.1mV) or deeper, in leads having a QRS complex with dominant R wave. The ischemic changes often resolve completely after the ischemic pain has subsided, or some abnormalities may persist. In general, transient changes in the T-wave, ST-segment, or conduction patterns point toward a cardiac source of the chest pain. Less frequently there is ST segment elevation during the ischemic symptoms, which signifies severe transmural myocardial ischemia due to an evolving ST-segment elevation myocardial infarction (STEMI), or rarely due to coronary arterial spasm (variant angina, or Prinzmetal's angina-see the video above). In some cases, the ischemic ST elevation may be preceded by the appearance of tall peaked symmetric T waves. 

A 65-year-old male, smoker, with a history of mild hypercholesterolemia, without any previous history of cardiovascular disease. He had a normal exercise ECG test 8 years ago. He has episodes of substernal pain lasting 15-20 minutes at rest with concomitant numbness in the upper extremities. What does the ECG show and what is the diagnosis?




The ECG shows sinus rhythm and a normal QRS axis but there is ST segment depression with an ischemic pattern in the leads  I,  V4, V5, V6 . The differential diagnosis is between unstable angina and non ST elevation myocardial infarction (NSTEMI) and the distinction between the two is based on cardiac troponin (which increases in NSTEMI but not in unstable angina). In this case, an increase in troponin was found and the diagnosis of NSTEMI was made. Coronary angiography showed two successive stenoses of 70-80% in the middle portion of the left circumflex coronary artery (LCX) which were treated with angioplasty and stent placement.

The exercise ECG test 

 Exercise ECG treadmill test (ETT), or a bicycle exercise ECG test is a useful test especially for people with intermediate risk of CAD for making the diagnosis of CAD, and  for people with high risk of CAD , or known CAD, not for diagnostic but mainly for prognostic reasons (to determine the prognosis, which can guide subsequent therapeutic decisions).
The exercise ECG test can be selected as a diagnostic test for CAD under the conditions that the patient is able to exercise, has no contraindications for an exercise test and has a normal baseline ECG [so that ischemic ST segment changes with exercise can be assessed and not obscured in the context of an abnormal baseline ECG. Conditions that can obscure exercise ECG findings are a left bundle branch block, a paced rhythm, Wolff Parkinson White syndrome, an ECG pattern of left ventricular hypertrophy with strain, a baseline ST depression of > 1mm (0,1 mV), or treatment with digitalis (digoxin). Usually in these conditions, the usefulness of an ECG exercise test is very limited and it is not selected as a diagnostic test].
Stress tests combined with imaging (e.g. myocardial perfusion scintigraphy scan-SPECT, or stress echocardiography) are more expensive but have a higher sensitivity and specificity than the ECG exercise test. They present a good option in order to obtain diagnostic and prognostic information (which can guide treatment decisions). 

These tests are preferred for people with a high pretest probability of CAD because they are more accurate and can provide information regarding the location and the extent of ischemia. They are also preferable for patients with known CAD (for prognostic assessment) and for people with intermediate pretest probability of CAD if they are unable to exercise, or if they have baseline ECG abnormalities that can limit the diagnostic accuracy of an exercise ECG test.
The resting echocardiogram
The resting echocardiogram is used to assess left ventricular ejection fraction (LVEF), which is an important prognostic factor that influences therapeutic decisions. It can also demonstrate segmental wall motion abnormalities of the left ventricle, in patients with a previous (old) myocardial infarction, or in patients with active acute myocardial ischemia (during the symptoms of an acute coronary syndrome).


An echocardiographic quiz (Video): A diabetic patient. Two echocardiographic views are provided in the video. Which are these views and what is the diagnosis?  The answer is provided in  the video (at the end).







Coronary CT angiography (CTA)

This noninvasive diagnostic test requires intravenous administration of a contrast agent.  It is discussed in a separate page, click on this link: CT coronary angiography-CTA (or multidetector computed tomography - MDCT )



Coronary angiography: 


The following patient categories should undergo coronary angiography to assess coronary anatomy for revascularization: Patients with high-risk features on non -invasive testing, or 
Patients with angina that limits their daily activities and does not respond adequately to medical treatment, or 
Patients presenting with an acute coronary syndrome (especially an ST elevation myocardial infarction which needs prompt revascularization with a primary PCI, or a non-ST elevation acute coronary syndrome with high, or intermediate risk features). (PCI= percutaneous coronary intervention).
Coronary angiography is performed by the insertion of catheters (plastic tubes of specific design and function) through the femoral, radial, or brachial artery into the aortic root in order to engage the ostium of the left and right coronary artery and to achieve a selective infusion of a contrast medium into the coronary arteries. The contrast medium can make the arteries visible on a fluoroscopic screen. Contrast medium, a viscous iodinated solution used to opacify the coronary arteries is usually injected by hand through a multivalve manifold. This is performed with the handle of the syringe raised up (the tip pointing down), in order to avoid injecting any small air bubbles into the arterial circulation (this way any small bubbles float up in the syringe). The contrast medium injection flow rate is usually 2-4 ml/sec, with volumes of 7-10 ml administered in the left coronary artery (LCA) and 2-6 ml in the right coronary artery. 

In coronary angiography, the source of the X-rays is under the patient and the image intensifier, which receives the x rays, is directly above the patient. The image intensifier can be described simply, for practical reasons, as the position of an observer looking at the heart. In right anterior oblique (RAO) views the image intensifier is on the right side of the patient, in left anterior oblique (LAO) views it is on the left side of the patient and in the anteroposterior (AP) view the image intensifier is directly over the patient with the X-ray beam traveling perpendicularly from back to front. In caudal views, the image intensifier is tilted towards the feet of the patient and in cranial views towards the head of the patient. The degrees of the angle that the image intensifier forms with the vertical line to the right or to the left, in RAO and LAO views respectively characterize the view. Moreover, the degrees of the angle between the image intensifier and the vertical axis at the cranial or caudal direction are also mentioned.
In the Right Anterior Oblique (RAO) projection the Image intensifier is angled above the right side of the patient’s chest and the heart is visualized from the right side. In the fluoroscopic image, the heart is on the right, its apex points to the right , the ribs go down to the right, the left anterior descending coronary artery (LAD) is on the right side and the circumflex coronary artery (LCX) and the spine are on the left.
In the Left Anterior Oblique (LAO) projection the Image intensifier is angled above the left side of the patient’s chest and the heart is visualized from the left side. A general description of the fluoroscopic image is the following: The spine is on the right side, the heart is on the left of the spine, the LAD is on the left and extends to the apex and the LCX is on the right. The ribs go down to the left.
In the Anterior- Posterior (AP) projection the Image intensifier is positioned directly above the patient’s mid-chest. The heart is visualized in the image from front to back.
In the Lateral projection, the Image intensifier is angled at a 90° angle to the left from the vertical axis, visualizing the heart from the far left side. In the fluoroscopic image, the LAD is on the far left and nearest to the sternum and the LCX and the spine are on the right side.
In Caudal views the Image intensifier is angled toward the patient’s feet, visualizing the heart from below. These projections tend to foreshorten LAD and elongate the LCx. So, they optimize visualization of LCx and OM (obtuse marginal branches of the LCX). 
The LAO caudal view of the left coronary artery, also called Spider view, permits a good visualization of the left main coronary artery (LM) and its bifurcation to the LAD and LCx. It is also an excellent view for the proximal and mid LCx, but a poor view for the LAD (considerably foreshortened).
In Cranial projections the Image intensifier is angled toward the patient’s head, visualizing the heart from above.  They tend to elongate the LAD and foreshorten the LCx. So these views optimize visualization of LAD, and its septal and diagonal branches.
Visualization of the right coronary artery (RCA)
The Right coronary artery is engaged in the LAO position. Initial imaging of the RCA in this view (LAO 30 degrees) gives the best view of ostial and proximal RCA disease. In the LAO projection, the RCA looks like the letter “C”, the spine is on the right and the ribs are pointed down to the left.
In the RAO projection the RCA looks like the letter “L. The ribs point down to the right and the spine is on the left side. The 45 degrees RAO projection permits an excellent visualization of the second (vertical) segment of the RCA and its branches (right ventricular and right marginal artery) and a good view of the posterior descending (posterior interventricular) artery, but the posterolateral branch (retroventricular artery) is not clearly defined.
The RAO projection at 120 degrees with cranial angulation at 10 degrees permits a good visualization of the third (horizontal) segment of the right coronary artery and of the retroventricular artery (posterolateral branch) and its branches. 



The procedure of coronary angiography demonstrated in a video (you tube channel  Media Space Plus  LINK https://www.youtube.com/watch?v=u7V1KeJBHKM


A Patient with NSTEMI Undergoing Complex PCI with stenting (a video by IsraelHeartOrg

https://www.youtube.com/watch?v=lHYw37M1A-Q

A video of a  percutaneous coronary intervention (PCI) of coronary artery bifurcation lesion

By Dr. Samin Sharma From Mount Sinai - New York


Useful links to comprehensive powerpoint presentations on CAD, emphasizing on the basics 
(the first by Dr. Haider Baqai and the second by Dr Ahmed Dabour, Hussain Salha and Osama Nofal )

A comprehensive powerpoint presentation of coronary artery disease

Coronary artery disease and myocardial infarction PPT


VIDEO : A case of coronary artery disease. Exercise stress echo and coronary angiography

A case of treadmill exercise stress echocardiography. Τhis is  a male patient 50 years old, smoker, with high cholesterol, who presented with mild dyspnea on exertion of  3 months duration. Physical examination and the ECG were without abnormal findings. Echocardiogram at rest was normal.  He was tested with a treadmill exercise ECG test combined with echo. The echocardiogram was performed before and immediately after exercise. The stress echocardiography findings, the coronary angiography, and treatment are shown and discussed.





NOTES 

Testing for coronary artery disease

Stress echocardiography

Stress echocardiography, introduced in 1979, is used for detection of coronary artery disease and for determination of prognosis. Stress (conditions that increase cardiac work, for example exercise or dobutamine administration) results in wall motion abnormalities in regions supplied by a stenosed coronary artery. These wall motion abnormalities can be recognized with echocardiography. 
Treadmill exercise echocardiography is the most widely used form of exercise echocardiography. Images are obtained before and immediately after symptom-limited treadmill exercise, for evaluation of changes in regional wall motion, ejection fraction and
systolic volume. The standard views in stress echocardiography are parasternal long- and short-axis and apical 4 chamber and 2 chamber views. The side by side comparison of rest and stress images can make possible the recognition of even subtle changes. Alternatively, the test may be performed during either supine or upright bicycling, a technique having the advantage, that images can be obtained during exercise. Interpretation of a stress echocardiogram depends on a visual assessment of left ventricular wall thickening and motion.
The hallmark of stress- induced ischemia (inadequate blood supply with respect to the demand) is the development of a new wall motion abnormality ( an abnormal contractile function of one or more myocardial segments) during stress or worsening of a wall motion abnormality that was present at rest.
Normally with exercise, ejection fraction markedly increases and all left ventricular walls become hyperdynamic (that is, they demonstrate increased contractility). 
For patients who are unable to perform physical exercise, pharmacologic stress testing with dobutamine (a β-1 adrenergic receptor agonist that increases contractility and heart rate), or the vasodilators dipyridamole or adenosine can be used. Dobutamine is the pharmacologic stress agent most commonly used in stress echocardiography.

Coronary angiography in stable CAD

Coronary angiography is indicated for the diagnosis of coronary artery disease when the risks of the procedure are outweighed by the likely benefits of accurate diagnosis and the patient is willing to consider a therapeutic procedure, if a significant problem is found. 
In stable coronary artery disease coronary angiography has a class I indication for purposes of revascularization, for patients whose angina is poorly controlled by medical treatment or who are intolerant of antianginal medications.
In patients with an abnormal stress test (for example ECG exercise test, or stress echocardiography, or myocardial perfusion scintigraphy-SPECT scan) the main indications for coronary angiography are the following: A stress test that is positive at a low workload (6 metabolic equivalents of oxygen consumption or less) or that is classified as high risk, is a class I (absolute) indication for coronary angiography, even if the patient is asymptomatic. 

High-risk findings in noninvasive (stress) tests for coronary artery disease 

 A high-risk ECG exercise test is characterized by an ST depression horizontal or downsloping of at least 2 mm in multiple leads or persisting into recovery for 5 minutes or more, or an ST elevation of 2 mm in leads without Q waves, a drop in blood pressure of > 10 mm Hg with exercise, or development of ventricular tachycardia with exercise.
 A high-risk stress test on a concomitant imaging modality (scintigraphy, echocardiography) is one showing left ventricle dilatation with stress, or a drop in ejection fraction with exercise, or multiple areas of ischemia suggesting multivessel disease, or an extensive area of reversible ischemia. 
A positive stress test without high-risk criteria is a relative indication for coronary angiography (class II indication): The doctor may decide to proceed with coronary angiography based on his clinical judgment and the patient's preference if the stress test is positive, with intermediate risk findings. 


Medical treatment of chronic coronary artery disease (CAD):

Modifiable risk factors such as hypertension, hyperlipidemia (dyslipidemia), obesity and smoking should be suitably treated, to stop the progress of CAD and reduce the risk of acute events. 

Lowering of LDL-cholesterol and the role of statins

Lowering of LDL-cholesterol has been shown to reduce cardiovascular disease event rates, not only in patients with CAD, but also in people with hypercholesterolemia (elevated blood cholesterol) but without diagnosed cardiovascular disease.
Trials have shown that in patients with evidence of CAD or vascular disease, with normal or elevated cholesterol levels, statins decrease mortality, the rate of myocardial infarction (MI) and stroke, and the need for coronary artery by-pass grafting surgery (CABG). These trials are the following: Scandinavian Simvastatin Survival Study (4S), Cholesterol and Recurrent Events (CARE), Long-term Intervention with Pravastatin in Ischemic Disease (LIPID), and Heart Protection Study (HPS).
 

 In CAD patients guidelines recommend achieving LDL-cholesterol levels <70 mg/dL or reduction in LDL-cholesterol by more than 50% with high-intensity treatment with statins (3-hydroxy-3-methylglutaryl coenzyme reductase inhibitors = HMG-CoA reductase inhibitors). The side effects of statin therapy, including myositis and hepatitis, are rare. Liver tests (transaminases-AST, ALT) and blood levels of CPK evaluation are recommended prior to initiation of therapy (or increase in dose) and 2- 3 months there- after. Blood tests are not necessary for routine follow-up of patients who are stable on statins and should only be measured in case of clinical suspicion of a side effect.
 Secondary goals of dietary, lifestyle, and pharmacologic therapies are HDL cholesterol > 45 mg/dL and triglycerides < 150 mg/dL. 

Nitrates

Nitrates are indicated in patients with angina. They provide a source of nitric oxide, which relaxes vascular smooth muscle and inhibits platelet aggregation. Nitrates are strong venodilators, and in higher doses they can also induce arterial dilatation. They reduce myocardial oxygen demand by reducing preload through venodilatation and in high doses they also induce coronary artery dilatation of stenotic vessels and intracoronary collaterals. Nitrates
prevent recurrent episodes of angina and increase exercise tolerance. Despite the improvement in symptoms, a survival benefit with the use of nitrates for chronic stable angina has not been shown by any randomized study. Dosing should allow for a nitrate-free interval of about 8 hours (usually at night) for preventing tolerance. (Tolerance is a gradual reduction in drug effectiveness during chronic treatment with nitrates). Use of long-acting tablets or transcutaneous delivery systems (nitrate patches) improves compliance but still necessitates a nitrate-free interval.
Side effects of nitrates: Oral nitrates should be taken with meals to prevent gastrointestinal disturbances, such as the burning sensation of gastrointestinal reflux (heartburn). Headache is common but is severity usually decreases with continued treatment and often can be controlled by decreasing the dose and/or paracetamol. Nitrates decrease blood pressure due to vasodilation, thus postural hypo- tension or dizziness can occur. Concurrent use of nitrates and PDE5 inhibitors like sildenafil (Viagra), tadalafil, etc can lead to severe hypotension and is absolutely contraindicated.


Beta-Blockers

Beta-Blockers competitively inhibit catecholamines from binding
to beta-adrenergic receptors. Beta-Blockers reduce myocardial oxygen demand through a negative inotropic effect (reduction in the force of myocardial contraction), a negative chronotropic effect (reduction of heart rate), and a reduction in left ventricular wall stress. When beta-blockers are used in the treatment of angina, a goal resting heart rate should be between about 55 -60 beats/minute. Beta-Blockers decrease mortality after myocardial infarction (MI). Among patients with stable angina without prior MI mortality reduction is not proven, although symptomatic improvement is well documented. Beta blockers also reduce mortality in patients with heart failure with reduced ejection fraction.
Side effects of beta blockers: The most important side effects are caused by blockade of beta -2 receptors. However, significant side effects do not occur frequently and as mentioned above, for some patient subsets beta blockers are a potentially lifesaving therapy. Thus we should try to offer this therapy (with caution) even to some patients considered to be at greatest risk for adverse effects.
Potential side effects: bronchoconstriction, masking of symptoms caused by hypoglycemic reaction among patients receiving treatment for diabetes, exacerbation of symptoms of peripheral vascular disease, and side effects from the central nervous system (CNS) and occasionally decreased libido (decrease in sexual drive), impotence, and reversible alopecia can occur. The CNS side effects such as somnolence, depression and vivid dreaming are thought to be related to the lipid solubility of these drugs (they are more frequent with the more lipid soluble beta- blockers).
In patients with a pre-existing conduction system disorder beta- blockers can lead to symptomatic bradycardia.
In patients with left ventricular (LV) systolic dysfunction beta blockers especially if they are not initiated in small doses can cause precipitation or worsening of heart failure (due to their negative inotropic effect). It is a fact that beta blockers are indicated for patients with LV systolic dysfunction, but they should be initiated in small doses and increases in dosage should be gradual. In this way, they are usually well tolerated and have beneficial effects on these patients. The condition of a patient with NYHA class III or IV heart failure should be stabilized before beta-blocker therapy is instituted.
Beta blockers are contraindicated in patients with bradycardia and caution is needed in those with reactive airway disease (asthma, bronchospasm), because they may aggravate bronchospasm (especially the non-selective beta-blockers)
Beta blockers have a small adverse effect on the lipid profile by mildly increasing LDL cholesterol and triglycerides and decreasing HDL cholesterol.
Drug interactions: The combination if a beta blocker with a non-dihydropyridine calcium channel blocker (verapamil or diltiazem) should be avoided (in most cases) because there is a risk of severe bradycardia or hypotension.

 Atenolol is renally excreted and should be used with caution in patients with renal dysfunction and in the elderly. 
[Doses of beta blockers usually prescribed for angina:
Metoprolol (tartrate
) 25–200 mg x 2 times/day
Metoprolol succinate (sustained release form) 25-200 mg x 1 time/day
Atenolol  25–200 mg PO one time/day
Propranolol 80–320 mg/day, divided in 2 -3 doses 
Propranolol (long-acting form) 80–160 mg x 1 time/day.
Carvedilol 6.25–25 mg x 2 times/day]

Calcium channel blockers (CCBs)

Calcium channel blockers (CCBs) are classified as dihydropyridines, or non-dihydropyridines (the latter category includes only verapamil and diltiazem). Calcium channel blockers positively alter myocardial oxygen supply and demand, through direct arterial vasodilatation. The non-dihydropyridines also have useful negative chronotropic and inotropic effects, which result in further lowering myocardial oxygen demand. Thus, CCBs have antianginal effect. Dihydropyridines, when used, should be given in the form of sustained-release preparations. CCBs must be avoided in patients with left ventricular systolic dysfunction, with the exception of amlodipine and felodipine, which are usually well tolerated in these patients.

Ranolazine

Ranolazine is a new antianginal agent, for the treatment of stable angina indicated for patients who remain symptomatic while on standard antianginal medical treatment. Its mechanism of action is probably through effects on sodium shifts and intracellular levels of calcium. Side effects include dizziness, nausea, constipation, and mild prolongation of the QT interval. Dosage is 500-1000 mg x 2 times/day.  Ranolazine should be used with caution in patients who are taking other medications that can prolong the QT interval and in patients with hepatic dysfunction.

Ivabradine

It inhibits the If current in the pacemaker cells of the sinus node, producing a bradycardic effect, without other hemodynamic effects.  As with beta- blockers,  also with ivabradine target resting heart rate should be about 55-60 /minute (dosage is individualized to achieve this heart rate). In patients with stable angina, it increases exercise tolerance and time from the onset of exercise to the onset of ischemia. 
Ivabradine is used as an adjunct to beta-blocker therapy for treatment of chronic stable angina pectoris in patients with inadequately controlled symptoms or as a substitute for beta-blocker therapy in patients with a contraindication or intolerance to beta-blockers.  It has shown improvement in anginal symptoms but did not show a reduction in adverse cardiovascular outcomes (new myocardial infarction or death). Ivabradine is not used in patients with atrial fibrillation and it is contraindicated in patients with bradycardic disorders (e.g. sick sinus syndrome), generally when resting heart rate is < 60/min prior to treatment, or severe hepatic dysfunction. 
Concomitant use with non-dihydropyridine calcium-channel blockers (diltiazem, verapamil) should be avoided because it increases plasma ivabradine concentrations, and may also exacerbate bradycardia
No dosage adjustment is required for patients with renal dysfunction and creatinine clearance 15-60 mL/minute and in patients with mild to moderate hepatic dysfunction. 
Dose range is 2.5-10 mg x 2 times/day.
Potential adverse effects: sinus bradycardia, a mild visual disturbance (due to an effect on retinal ion channels )

Antiplatelet Therapy

An acute coronary syndrome is usually caused by a platelet-rich thrombus (an intravascular blood clot) occurring at the site of a coronary artery stenosis, after rupture of an atheromatic plaque. Antiplatelet medications decrease morbidity and mortality in patients with coronary artery disease (CAD) or peripheral vascular disease, because they decrease the rate of myocardial infarction. For patients with stable CAD, low-dose aspirin (80–100 mg daily) is as effective as higher doses (300 mg). In patients with CAD, aspirin therapy achieves a 26% reduction in myocardial infarction. The number of patients needed to treat to prevent a myocardial infarction is 83. The Antiplatelet Trialists’ Collaboration Study demonstrated in high-risk cardiovascular patients treated with antiplatelet therapy a reduction in myocardial infarction, stroke, and death. Thus, guidelines recommend in all patients with CAD indefinite (life-long) aspirin treatment for the secondary prevention of cardiovascular events. In patients with allergy or intolerance to aspirin, clopidogrel is given instead of aspirin. Among patients with allergy or intolerance to aspirin, clopidogrel has been shown to decrease the frequency of fatal and nonfatal vascular events in peripheral arterial, cerebral arterial disease, and CAD.


Dual antiplatelet therapy with aspirin and clopidogrel or aspirin plus one of the newer antiplatelet agents, ticagrelor or prasugrel, is administered to patients with an ACS ( unstable angina, or acute myocardial infarction). Aspirin plus clopidogrel is administered after a percutaneous coronary intervention -PCI (angioplasty usually with stenting) in cases of stable CAD for 1-2 months after intracoronary placement of  a bare metal stent (BMS) or for 6-12 months after placement of a drug-eluting stent-DES (these stents are preferred due to a lower rate of in-stent restenosis of the artery). In patients treated with PCI for an acute coronary syndrome (ACS) aspirin plus clopidogrel, or aspirin plus ticagrelor, or aspirin plus prasugrel are given preferably for 12 months (in patients with a BMS or a DES). When the appropriate time of dual antiplatelet therapy elapses, antiplatelet therapy only with aspirin continues indefinitely.



Revascularization for coronary artery disease (CAD)

Besides medical treatment, other treatment options for CAD are therapies, that achieve revascularization, i.e. the restoration of blood flow to myocardial territories with reduced blood flow, due to significantly stenotic or occluded arteries. These treatment options include percutaneous coronary intervention i.e. percutaneous transluminal angioplasty with stent placement (PCI) or coronary artery by-pass grafting (CABG). CABG  compared with medical treatment has been proven to decrease cardiovascular mortality in specific patient subsets with CAD. 
Randomized trials of patients with mild to moderate stable angina have shown an improved survival rate for patients treated with
initial CABG, compared with those treated with initial medical treatment, in the following circumstances:
A left main (LM) stenosis > 50% of the diameter,
Triple- vessel disease (significant stenosis of three coronary arterial vessels)
 Double-vessel disease (significant stenosis in 2 arteries) with a proximal left anterior descending LAD lesion, 
Double vessel disease with abnormal left ventricular systolic function, or a strongly positive exercise test result,
A proximal LAD lesion causing documented myocardial ischemia. 
Therefore, the above patient subsets, are these that have a survival benefit from surgical revascularization (coronary artery by- pass grafting-CABG).
 In patients with stable CAD, PCI has been shown to effectively improve anginal symptoms and quality of life in comparison with medical treatment. For patients with stable CAD and significant coronary lesions (i.e. lesions with stenosis ≥50%  that causes reversible ischemia in non-invasive functional tests, or with  reduced fractional flow reserve: FFR < 0.8  measured invasively at the time of coronary arteriography, or with stenosis ≥ 90%) in one or more arteries, an initial PCI results in the following : A significant reduction in anginal symptoms and in the need for hospitalization for urgent revascularization. (For an explanation of FFR see below) Thus, PCI is a reasonable choice for these patients, especially if there are anginal symptoms despite medical treatment or evidence of substantial ischemia. However, PCI has not been shown to reduce the composite endpoint of MI or death in these patients. A decrease in mortality has not been proven with PCI in randomized controlled trials (RCTs) in comparison with optimal medical treatment. 
Thus, a trial of optimal medical therapy to control symptoms and reduce mortality is justifiable and cost-effective, for patients with stable coronary disease not associated with anatomic features for which revascularization has been shown to prolong life, and not accompanied by anginal symptoms resistant to medical treatment.
 PCI in patients with chronic CAD  should not be performed for coronary lesions causing stenosis of the arterial diameter <50 %, or a stenosis 50-90% with FFR > 0.8, or without documented substantial ischemia on non-invasive testing.
The fractional flow reserve (FFR), during maximum hyperemia (usually induced by vasodilation of the peripheral coronary circulation-the arterioles- with intravenous adenosine) is the ratio of the pressure distal, divided by the pressure proximal to a coronary arterial stenosis. These pressures can be measured at coronary angiography with the appropriate equipment ( a pressure wire that is advanced through the arterial stenosis) after maximal peripheral vasodilation of the coronary arterial bed with the administration of adenosine. 
An FFR (distal pressure/proximal pressure) <0.80 documents the hemodynamic severity of the coronary lesion and predicts a clinical benefit from PCI, whereas an FFR greater than 0.80 has been correlated with clinical harm from PCI, which should not be performed in this case. FFR measurement is not necessary if noninvasive tests have shown that a coronary stenosis causes substantial reversible ischemia, because this is an adequate proof,  that the coronary lesion is hemodynamically significant. FFR measurement is also not necessary if there is a diameter stenosis of the arterial lumen  ≥ 90%.
Revascularization, with either PCI or CABG (depending on the extent and anatomic-angiographic characteristics of coronary artery disease), is appropriate, for the following patient categories:
Patients who remain symptomatic despite intensive medical (drug) therapy.
Patients with evidence of ischemia of substantial severity, or involving an extensive myocardial region, regardless of the presence or absence of symptoms. Severe or extensive ischemia is documented by high-risk findings in functional tests, such exercise ECG testing, stress echocardiography, or myocardial perfusion scintigraphy (SPECT imaging).
Patients with stable (or unstable)  CAD who meet certain anatomic criteria: Significant LM coronary artery disease, significant three-vessel disease, or significant two-vessel coronary artery disease with left ventricular systolic dysfunction ( EF< 50%), or significant stenosis at the proximal segment of the LAD.

Patients with a STEMI (ECG findings of ST elevation, or new or presumably new left bundle branch block, or ECG findings of a true posterior myocardial infarction- click on the link to see chapter about the ECG for details- and symptoms compatible with an acute coronary syndrome ) in the first 12 hours of symptom onset. For these patients, a primary PCI is the preferred reperfusion strategy.
Patients with unstable angina or NSTEMI and high (or even intermediate) risk features. 


The choice between PCI and CABG for revascularization in coronary artery disease (CAD) and the SYNTAX score

In patients with stable CAD and an indication for revascularization (eg anginal symptoms despite medical treatment, or findings of severe or extensive ischemia in noninvasive tests), the choice is between PCI and CABG. In such patients significant lesions in one or two coronary arteries (ie 1 or 2 vessel disease) with a normal, or near normal left ventricular contractile function generally favor the choice of PCI, if the anatomy of the lesions is suitable (eg lesions of small to moderate length, without severe calcification, without total vessel occlusion, or vessel tortuosity etc). The presence of left main or 3 vessel disease generally favors CABG, but if the SYNTAX score is low, then PCI can also be an appropriate option. The SYNTAX score is used to grade the anatomic complexity of the coronary lesions and thus the difficulty of PCI, in patients with left main or multivessel disease and generally, a high SYNTAX score suggests selecting CABG and not PCI as the revascularization strategy (see below).
In general, CABG improves survival among patients with complex multivessel or left main CAD. Patients especially likely to benefit from CABG are those with  more severe, more diffuse and complex CAD (a high SYNTAX score) and apart from the extent of CAD, also the presence of  diabetes, left ventricular dysfunction, or mitral valve dysfunction (moderate to severe) are factors that tend to support the choice of CABG.  
The SYNTAX score is an anatomic scoring system, based on the coronary angiogram, which quantifies CAD lesion complexity in patients with multivascular and/or left main disease and predicts clinical outcomes after percutaneous coronary intervention (PCI) or coronary artery by-pass grafting (CABG). The drawback to this score is that it does not include clinical features, such as the age of the patient, left ventricular function, the presence of diabetes, chronic renal failure or neurologic impairment, which also profoundly affect the treatment decision.
A newer development is the SYNTAX score II, which apart from the anatomy of the coronary lesions, also takes into account some clinical variables, such as age, sex, renal function (creatinine clearance), the presence of peripheral vascular disease or chronic obstructive lung disease and the left ventricular EF.
The SYNTAX score was initially established by the SYNTAX ( Synergy between PCI with Taxus and Cardiac Surgery) study, which randomly assigned 1800 patients with either three-vessel or left main stable coronary artery disease to CABG or PCI.  For each patient, the SYNTAX score was determined, as a measure of the extent and complexity of CAD and the anticipated complexity and risk of PCI.
The complexity of coronary artery disease (CAD) and the risk associated with PCI is classified with the SYNTAX score as:
 low ( score ≤22), 
intermediate ( score 23 - 32), 
or high (score ≥33).
As a general rule, this randomized study demonstrated that patients who had SYNTAX scores >34 appeared to do much better with bypass surgery than those with lower SYNTAX scores, in whom PCI was just as good for major adverse cardiac events, with lower stroke rates.
In patients with the least complex three-vessel disease (SYNTAX score ≤22), the  SYNTAX trial showed that PCI was non-inferior to CABG.
In patients with more complex three-vessel disease (SYNTAX score ≥23), CABG was superior to PCI.
In the SYNTAX study, 
in patients with isolated left main coronary artery disease or left main coronary artery disease and single-vessel coronary artery disease (SYNTAX score <33) the outcomes of the two procedures were the same. 
However, in patients with left main and two- or three-vessel coronary artery disease (SYNTAX score ≥33), the outcome was better with CABG (in this group CABG resulted in a significant reduction in the rate of the composite endpoint of death, myocardial infarction, stroke, or repeat revascularization compared with PCI). 
To calculate the SYNTAX score for a patient the following site provides you with directions and a calculator:
http://www.syntaxscore.com/

Choice between PCI and CABG in patients with acute coronary syndromes

The evidence for the comparison of these two methods of revascularization is almost entirely based on studies of patients with stable CAD. Nevertheless, the recommendations for CABG are commonly extended to include patients with unstable angina and stable NSTEMI, with a high SYNTAX score. 
For patients with acute STEMI, the best initial treatment is prompt reperfusion therapy with either PCI or fibrinolytic therapy. In patients with acute  STEMI,  PCI restores coronary blood flow more rapidly, preserves more myocardium, and improves outcomes, compared with CABG. CABG in patients with acute STEMI  is reserved for those who have a coronary anatomy that is not amenable to PCI or who have mechanical complications, such as ventricular septal defect, myocardial rupture, or papillary muscle rupture with acute, severe mitral regurgitation.


The cardiac syndrome X 

This term refers to those patients with a history of angina (usually a typical history), a positive ECG exercise test or an imaging test positive for ischemia and angiographically normal coronary arteries. Cardiac syndrome X is much more common in women
than in men. The prognosis of these patients is good, but they are
often highly symptomatic and can be difficult to treat. The most probable cause of this condition is an abnormal vasodilator response of the coronary microvasculature to stress
 (e.g. during exercise). 





The acute coronary syndromes (unstable angina and acute myocardial infarction STEMI or NSTEMI) 

The term acute coronary syndrome (ACS) encompasses a group of conditions in which acute myocardial ischemia occurs secondary to a sudden disruption in coronary blood supply to a territory of the heart. This disorder ranges from myocardial tissue ischemia (unstable angina) to the development of necrosis (non-ST or ST elevation myocardial infarction -NSTEMI and STEMI respectively).
In an ST-elevation myocardial infarction
 (STEMI), there is a complete occlusion of the coronary artery. This is characterized by ST elevation on ECG.
In non-ST elevation myocardial infarction (NSTEMI) or unstable angina, there is a partial occlusion of a coronary artery and this usually manifests on the ECG by ST segment depression or T wave inversion. The severity of ischemia depends on the degree of obstruction, the extent of collateral circulation and the presence of emboli. In unstable angina, there is no myocardial necrosis and troponin is not raised., whereas in non-ST elevation myocardial infarction (NSTEMI) there is a rise in troponin, indicating the presence of myocardial necrosis of variable extent.
These conditions are classified according to the findings in the electrocardiogram (ECG) and biochemical markers of myocardial necrosis. An ACS is almost always associated with rupture of an atherosclerotic plaque and thrombus formation with partial or complete occlusion of a coronary artery.
The acute coronary syndromes (ACS) are a major cause of mortality since they account for an estimated 30% of all deaths worldwide. They are more common in males, but they may be underdiagnosed in women.  

Clinical presentation of patients with an acute coronary syndrome (ACS)

Patients with an acute coronary syndrome (ACS) usually have a new onset of chest pain, chest pain at rest, or a deterioration (worsening) of pre-existing angina. In patients with an ACS, the chest discomfort is usually a crushing central retrosternal or left-sided (on the left of the sternum) pain. The pain is often severe and it may radiate to the jaw, neck or arm (usually the left and less commonly to both arms).
Often the patient does not have a previous history of stable angina (a history of long-standing angina is present in only 20% of the patients with an ACS)However, some patients manifest atypical presenting symptoms such as dyspnea, a sense of "indigestion" or epigastric pain, syncope, hypotension, or an acute confusional state (especially in elderly patients), or rarely pleuritic chest pain.
Apart from chest pain, other coexisting features that are often present include a sense of impending doom (angor animi), sweating, pallor, dyspnea (breathlessness), nausea and vomiting.
Atypical presentations occur in about 20% of ACS patients, particularly in those with dysfunction 
of the autonomic nervous system  (some patients with diabetes mellitus and elderly patients). A myocardial infarction without chest pain is an atypical presentation, referred to as "a silent myocardial infarction".

Physical examination in acute coronary syndromes   

Common findings that may be present include Levine’s sign: the patient describes the discomfort with a clenched fist on the chest (specificity about 80%), pallor, diaphoresis (sweating) and anxiety, occasionally a fourth heart sound and low-grade pyrexia can be present in some cases.
Physical examination can also detect clinical signs indicating an increased severity of the patient's condition such as hypotension, basal crackles, or a systolic apical murmur of mitral regurgitation.

The ECG in unstable angina or acute myocardial infarction 

 ST depression and/or T wave inversion are highly suggestive for unstable angina or NSTEMI, particularly if they are new or associated with anginal chest pain. In some cases, the 12-lead ECG may be normal in patients with an ACS, but a normal initial ECG can change later. The ECG should be repeated when the patient is in pain, or if there is a clinical suspicion of an ACS. and continuous ST-segment monitoring is recommended. In STEMI, complete occlusion of a coronary artery manifests on the ECG with persistent ST-elevation or a new left bundle branch block. (A transient ST elevation can be seen in coronary vasospasm, a condition called Prinzmetal’s angina). 
ECG features of STEMI are the following:
in at least 2 adjacent limb leads: 1 mm ST elevation or
in at least 2 contiguous precordial leads 2 mm ST elevation or new
onset left bundle branch block (LBBB). 


A man 70 years old with crushing pain on the center of the chest, nausea, and vomiting. The symptoms started 1 hour ago. What are the ECG findings, which is the diagnosis and what is the preferred treatment?


Answer

Rhythm: sinus with first-degree atrioventricular block (prolonged PR interval). ST segment elevation in leads II, II, avF, diagnostic of an acute inferior wall myocardial infarction (acute inferior STEMI). Q waves are also developing in leads III and avF. The ST segment depression in leads avL and I represent "mirror changes". The ST depression in leads V1, V2 is indicative of a concomitant posterior wall infarction. 
Management consists of initial measures such as continuous rhythm monitoring, antiplatelet treatment, morphine, metoclopramide( for vomiting), oxygen if needed (if hemoglobin saturation is<95%), normal  saline infusion if there is hypotension, anticoagulation, and emergent coronary reperfusion treatment : Primary PCI if it can be performed within 120 minutes by an experienced team, or otherwise fibrinolysis as soon as possible (within 30 minutes from the first medical contact/ provided there are no contraindications to fibrinolysis).


A patient with crushing pain in the central area of the chest, sweating, and pallor. Which is the culprit artery?



ANSWER  An acute ST elevation myocardial infarction with ST elevation in leads I, avL, V1-V6
ST depressions in leads II, III, AVF are reciprocal ("mirror") changes. IT is an extensive anterior acute STEMI and this type of STEMI is usually the result of an occlusion of the LAD ( This case is courtesy of Dr. Kazi Ferdous-  Dhaka Medical College and Hospital). The patient was treated successfully with primary PCI.   You can see below this patient's left coronary angiography before (Image A) and after (Image B) the procedure of primary PCI  ( LM left main coronary artery LAD left anterior descending artery  LCX left circumflex artery)

A



B




Biomarkers in acute myocardial infarction

The best biochemical markers of myocardial infarction are the cardiac troponins: cardiac troponin I and T have a  high sensitivity and specificity for acute myocardial infarction. Troponin is useful for the diagnosis, as well as for the assessment of the prognosis in patients with an acute coronary syndrome (ACS).
A meta-analysis has shown that an elevated troponin level in patients with ACS without ST-segment elevation is associated with a nearly 4-fold increase in cardiac mortality rate.  

Many trials (such as the TIMI IIIB, GUSTO IIa, GUSTO IV-ACS, and FRISC trial) demonstrated a direct correlation between the level of cardiac troponin (TnI or TnT) and the rate of adverse cardiac events and mortality in patients with ACS.
 Cardiac troponin should be requested on patient presentation and 12 hours after onset of symptoms. Troponin is a marker of myocardial necrosis which starts to be elevated in acute myocardial infarction at 2-4 hours after symptom onset, peaks at about 12-18 hours, and usually remains elevated for approximately 10-14 days.
Important Note: In a case of a suspected acute coronary syndrome (ACS) appropriate treatment must start as early as possible (including emergency myocardial reperfusion if there is a STEMI) and so do not wait for the result of troponin to start treatment.
Troponin can also be elevated in other conditions and should not be used in isolation for the diagnosis of acute myocardial infarction. Other conditions in which troponin may be elevated are the following: 
myocarditis, pericarditis, acute heart failure,  pulmonary embolism, prolonged tachyarrhythmia, renal failure, and sepsis.
Creatine phosphokinase-MB (CPK-MB), is the form of the enzyme creatine phosphokinase which is more specific to the heart muscle. It is a good biomarker indicating myocardial necrosis, although it is less sensitive and less specific compared to cardiac troponin. In the setting of myocardial infarction, plasma CK-MB concentrations start to rise about 4-6 hours after the onset of chest pain,  peak at 12-24 hours and return to normal (baseline) levels within 24-48 hours. A reliable estimate of the size of the infarct can be provided by the area under the concentration-time curve for CK-MB created with serial measurements of its levels. CK-MB values can also rise in conditions different than ACS, such as trauma, heavy exertion, and skeletal muscle disease (eg rhabdomyolysis).


An overview of the initial treatment of an acute coronary syndrome (unstable angina or acute myocardial infarction)


Establish intravenous access (preferably two large bore peripheral venous catheters). Start pulse oximetry and continuous ECG monitoring, and give supplemental oxygen if the oxygen saturation (SaO2) is less than 95%, or if the patient manifests dyspnea (breathlessness), or signs and symptoms of acute heart failure. 
ECG monitoring is very useful because most deaths caused by an acute myocardial infarction occur early and are due to ventricular fibrillation (VF). Prompt electric defibrillation is mandatory in cases of VF.
Give immediately aspirin 250-325 mg (usually we give 1/2 tablet 500 mg, which is chewed by the patient, for quick absorption). Apart from aspirin, a second antiplatelet agent is given to patients with an ACS: A loading dose of clopidogrel (300 to 600 mg PO once), or ticagrelor (180 mg PO once), or prasugrel (60 mg PO once), improves outcomes. Prasugrel and ticagrelor are more rapid in onset and may be preferred in cases of urgent percutaneous coronary intervention (PCI).
 If there is active chest pain, nitroglycerin is given sublingually or by spray, provided there are no contraindications (contraindications include hypotension <100 mmHg, acute inferior STEMI with right ventricular infarction, severe stenosis of the aortic valve, recent use of a phosphodiesterase inhibitor-eg sildenafil within the last 24 hours).

Relief of pain is important because it is associated with sympathetic activation. Sympathetic activation causes vasoconstriction and increases the workload of the heart. For the relief of pain intravenous (IV) morphine is administered: 2.5-5 mg over 4-5 minutes. It can be repeated, if necessary, every 5-15 minutes. Prior to each dose of morphine, the rate of respiration (number of breaths/minute), the heart rate and blood pressure is assessed, because morphine can cause suppression of the respiratory center and bradycardia or hypotension due to stimulation of the parasympathetic nervous system. The latter two conditions are treated with IV atropine 0.5 mg. In the case of respiratory depression, the action of morphine can be reversed by the intravenous (IV) administration of naloxone (an antidote for opioid drugs)  0.4-0.8 mg. Also, because morphine can cause nausea or vomiting, the antiemetic metoclopramide (Primperan) 5-10 mg is administered IV.
To patients with an ACS besides antiplatelet drugs, aspirin and clopidogrel (ticagrelor, or prasugrel can be used instead of clopidogrel), also anticoagulant treatment must be initiated with low molecular weight heparin or unfractionated heparin, or bivalirudin.
Bivalirudin is recommended as an anticoagulant for patients with a known or suspected history of heparin-induced thrombocytopenia.
Oral treatment with beta-blockers should be administered early to patients with ACS, (or an initial intravenous dose, followed by oral treatment) and continued thereafter unless there is a contraindication. Contraindications of beta-blockers include bradycardia, hypotension, acute congestive heart failure, severe bronchospasm. Non-stabilized patients with acute heart failure are not treated with beta-blockers, but beta blockers (especially carvedilol, bisoprolol, or metoprolol) are indicated in the treatment of patients with chronic heart failure with systolic left ventricular dysfunction after the acute non-compensated phase. 
Prompt initiation of statin therapy (high dose of a statin e.g. atorvastatin 40-80mg/day) regardless of the baseline levels of LDL cholesterol is recommended during hospitalization in all patients with an acute coronary syndrome (ACS) to promote plaque stabilization and to restore endothelial function. 
Timely treatment of the patient with an ACS (and especially STEMI) is very important, thus minimizing delays in the administration of appropriate treatment and in the transfer to the appropriate facility (hospital) is associated with improved outcomes.
To minimize patient delay, the public should be made aware of how to recognize common symptoms of acute myocardial infarction and instructed to call the emergency services immediately on such an occasion.

Reperfusion treatment in patients with STEMI

In patients with ST segment elevation myocardial infarction (STEMI) reperfusion therapy (restoration of flow in the occluded coronary artery) is indicated in all patients with symptoms of <12 h duration and persistent ST-segment elevation or new (or presumed new) left bundle branch block (LBBB). 
Reperfusion therapy (preferably primary PCI) is also indicated even if symptoms have started >12 h before, if there is evidence of ongoing myocardial ischemia. Primary PCI is defined as an emergent percutaneous catheter intervention in the setting of STEMI, without previous fibrinolytic treatment. Fibrinolytic treatment is defined as the IV administration of a drug that can achieve thrombolysis, ie the lysis (breakdown) of thrombus in a blood vessel. (General indications of thrombolysis include ST elevation myocardial infarction, acute ischemic stroke, and a very large pulmonary embolism causing hypotension). Primary PCI is the preferred reperfusion strategy in patients with STEMI, provided it can be performed within guideline-mandated times (within 120 minutes from first medical contact), by an experienced team. When primary PCI cannot be performed within the guideline-mandated time limits, then fibrinolytic treatment is indicated (provided that specific contraindications to thrombolysis are not present). An acceptable time interval from first medical contact to primary PCI is ≤120 min (≤90 min if the patient presents early after symptom onset with a large area at risk, ie a large estimated area of acute myocardial ischemia). If this time criterion cannot be met, consider fibrinolysis.
If fibrinolysis is chosen as reperfusion strategy (eg in a STEMI patient if primary PCI is not available within 2 hours from first medical contact), then current guidelines recommend coronary angiography to be performed 3-24 hours after successful fibrinolysis.
Another indication for primary PCI is for STEMI patients with severe acute heart failure or cardiogenic shock unless the expected PCI related delay is excessive and the patient presents early after symptom onset.
In STEMI, the sooner reperfusion of the culprit coronary artery is achieved the better the outcome for the patient. Hospitals and emergency medical services (EMSs) managing patients with STEMI must monitor delay times and work to achieve the following quality targets: 
• first medical contact to first ECG ≤10 min
• first medical contact to reperfusion therapy, if fibrinolysis is used ≤30 min. In case of primary percutaneous coronary intervention (primary PCI) ≤90 min (≤60 min if the patient presents within 2 hours of symptom onset or directly to a PCI- capable hospital). Note that 90 minutes is the preferred time interval for primary PCI, but a time interval up to 120 minutes is acceptable.
The time intervals mentioned above, are defined as the time from first medical contact to the beginning of thrombolytic drug administration, or the time from first medical contact to the passage of the angioplasty wire into the culprit artery, during primary PCI.

Guidelines regarding procedural aspects of primary PCI 

Primary PCI should be limited to the culprit vessel with the exception of cardiogenic shock in the presence of multiple truly critical stenoses,(≥90% diameter) or persistent ischemia after PCI of the supposed culprit lesion. When performing primary PCI, routine thrombus aspiration should be considered. Stenting is recommended (over balloon angioplasty alone) for primary PCI. A drug eluting stent (DES) should be preferred over a bare metal stent (BMS) if the patient is likely to be compliant and has no contraindications to prolonged dual antiplatelet therapy (DAPT), such as an indication for oral anticoagulation, or estimated high long-term bleeding risk. Radial access should be preferred over femoral access if performed by an experienced radial operator, otherwise, femoral access is used. The radial approach has been shown to reduce the incidence of acute bleeding events on the arterial puncture site.

Antithrombotic treatment in STEMI patients treated with primary PCI

Aspirin is given and a platelet ADP-receptor blocking drug is recommended in addition to aspirin. Options are: 
Ticagrelor or 
Prasugrel (if there is no history of prior stroke or transient ischemic attack and age <75 years) or
 Clopidogrel.
 Glycoprotein (GP)  IIb/IIIa inhibitors should be considered if there is angiographic evidence of massive thrombus, slow reflow or no-reflow or a thrombotic complication.  Upstream use of a GP IIb/IIIa inhibitor (versus use in the catheterization lab ) may be considered in high-risk patients being transferred for primary PCI. 
If a  GP IIb/IIIa inhibitor is administered options include Abciximab, Eptifibatide, or Tirofiban
An injectable anticoagulant must be used in primary PCI and this anticoagulant can be bivalirudin, or enoxaparin, on unfractionated heparin. Fondaparinux is not recommended for primary PCI. Moreover, the use of fibrinolysis before planned primary PCI is not recommended. (The text of the chapter continues after the images)

A female patient 55 years old, smoker, came to the emergency department with pain in the lower sternal area and epigastrium, vomiting, and perspiration. Suddenly, she lost consciousness and collapsed. From the images below, can you tell what happened to the patient, what was the cause and what kind of treatment she has received ?  
The images of this case are courtesy of Dr. Alma Sthela Arrioja.

1
Cardiac arrest due to ventricular fibrillation (VF)


2
acute myocardial infarction (inferior wall STEMI)

3
coronary angiography

4
coronary angiography (right coronary artery-RCA)

Image 1, shows that the patient had an episode of cardiac arrest caused by ventricular fibrillation (VF) The ECG shows the characteristics of VF with rapid, chaotic, irregular deflections of varying amplitude and no identifiable P waves, QRS complexes, or T waves. This irregular electrical activity inevitably causes the loss of any effective ventricular contraction, resulting in immediate loss of pulses and cardiac output. Treatment consists of immediate CPR (cardiopulmonary resuscitation with a ratio f 30 chest compressions (cardiopulmonary resuscitation with a repeated sequence of 30 chest compressions and 2 rescue breaths. External electrical defibrillation should be performed as soon as possible (immediately when the defibrillator is brought, connected to the patient and charged) starting with 200 Joules in the adult ( in children 2 Joules/kg body weight).
Image 2 shows that, obviously, successful CPR with defibrillation was performed on this patient, since this subsequent ECG, shows sinus rhythm (note the positive P waves in leads I and II and the negative ones in AVR) with tachycardia (about 110-120 pulse/min) and a clear ECG picture of an acute inferior wall STEMI (with ST-segment elevation in the inferior leads and reciprocal ST depression in leads I and avL). Thus, the cause of the VF was acute myocardial ischemia (here the acute phase of an inferior STEMI).  In general, acute inferior STEMI is caused by an  RCA lesion in 80% of cases, or an LCX lesions in 20% of cases.The best definitive treatment for an acute STEMI is primary PCI of the culprit coronary artery (if this is available within the appropriate time limits- otherwise the second best option is fibrinolysis).
Images 3 and 4, show that the patient has undergone a successful primary PCI of a totally occluded right coronary artery (RCA). Image 3 shows the initial coronary angiography of the proximally occluded RCA and image 4 shows the same artery after PCI, with successful reperfusion. 

Fibrinolysis in patients with acute STEMI

Fibrinolysis (thrombolysis) is chosen as a reperfusion strategy in patients with acute MI and ST elevation or LBBB (not known to be old) presenting < 12 hours from symptom onset if primary PCI is not available within 120 minutes from first medical contact.
Fibrinolysis should also be considered for STEMI patients presenting early (<2 h after symptom onset) with a large estimated myocardial area at risk (ECG or echocardiographic evidence of a large infarction) and low bleeding risk,  if estimated time from first medical contact to primary PCI is >90 min.
These two indications for fibrinolysis apply only when there is no contraindication to thrombolysis.

Contraindications to fibrinolysis (thrombolysis)

Absolute contraindicationsActive bleeding
Prior intracranial hemorrhage, other strokes or neurologic
events within
1 year, intracranial neoplasm
Recent major surgery (
<6 weeks) or major trauma (<2 weeks)
Recent vascular puncture in a noncompressible site (
<2 weeks)
Suspected aortic dissection
Relative contraindicationsActive peptic ulcer disease or recent gastrointestinal bleeding
(
<4 weeks)
Severe uncontrolled hypertension on presentation (BP
>180/110 mm Hg) or chronic severe hypertension
Cardiopulmonary resuscitation
>10 min
Prior nonhemorrhagic stroke
Pregnancy
Bleeding diathesis or INR
>2  

Coronary artery bypass grafting (CABG) for acute ST elevation myocardial infarction (STEMI) patients:
In contrast to primary PCI or fibrinolysis, CABG has a limited role in the acute management of STEMI. However, CABG is indicated alone or as part of the surgical treatment in cases of failed PCI, coronary anatomy of high risk for PCI, surgical repair of a mechanical complication of STEMI (eg, ventricular septal rupture, rupture of ventricular free wall, or severe mitral regurgitation from papillary muscle dysfunction or rupture).



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Bibliography and links

Archbold RA. Comparison between National Institute for Health and Care Excellence (NICE) and European Society of Cardiology (ESC) guidelines for the diagnosis and management of stable angina: implications for clinical practice. Open Heart. 2016;3(1):e000406. doi: 10.1136/openhrt-2016-000406. eCollection 2016.
LINK https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908898/pdf/openhrt-2016-000406.pdf

Smith JN, Negrelli JM, et al. Diagnosis and management of acute coronary syndrome: an evidence-based update. J Am Board Fam Med. 2015;28:283-93.
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Fathala A.  Myocardial Perfusion Scintigraphy: Techniques, Interpretation, Indications and Reporting Ann Saudi Med. 2011; 31: 625–634.
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Noninvasive Testing for Coronary Artery Disease. 
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LINK https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0087137/pdf/PubMedHealth_PMH0087137.pdf



Coronary-Artery Bypass Grafting versus PCI (blogs NEJM org.)

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Valgimigli M, Serruys PW, et al. Cyphering the complexity of coronary artery disease using the syntax score to predict clinical outcome in patients with three-vessel lumen obstruction undergoing percutaneous coronary intervention. Am J Cardiol 2007;99:1072-1081.

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2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes



2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation


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ESC Guidelines on the diagnosis and treatment of peripheral artery diseases

2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management

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