Congestive heart failure diagnosis and treatment / and A case of Heart Failure from ischemic cardiomyopathy. ECG, echo, SPECT, coronary angiography and treatment.

Congestive heart failure diagnosis and treatment / and A case of Heart Failure


One of my medical videos. A case of ischemic cardiomyopathy The patient presented with effort dyspnea, in the context of coronary artery disease and a previous myocardial infarction. The ECG, the echocardiogram, the myocardial perfusion scan (SPECT) and the coronary angiography of the patient are presented and the appropriate treatment is discussed.


Definition of heart failure and general considerations 

Definition : Heart failure (HF) is a progressive pathologic condition. It is defined as a clinical syndrome that results from any structural or functional abnormality of the heart  resulting in a reduced cardiac output and/ or elevated intracardiac pressures at rest or during stress (physical activity) and is characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) and/or signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema). HF can also be defined as an abnormality of cardiac structure or function that impairs the ability of the left ventricle, or the right ventricle, or both ventricles, to eject blood, or to fill with blood,  leading to failure of the heart to deliver blood and oxygen at a rate commensurate with the requirements of the metabolizing tissues, despite normal filling pressures, or the situation in which the heart is able to deliver to the tissues blood and oxygen at a sufficient rate only at the expense of increased filling pressures. HF may involve the left heart, the right heart, or be biventricular.
HF is characterized by dyspnea and/or fatigue on exertion (and occasionally at rest) and evidence of fluid retention, which can manifest as peripheral edema or pulmonary congestion. Clinically HF can be defined, as a syndrome in which patients have typical symptoms (e.g. breathlessness, ankle swelling, and fatigue) and signs (e.g. elevated jugular venous pressure, pulmonary crackles, and displaced apex beat), resulting from an abnormality of cardiac structure or function.
The prevalence of HF is increasing. The prognosis is severe for symptomatic HF (50 % or more of patients hospitalized for heart failure die within the next 5 years.) HF is a significant cause of morbidity and mortality. Death in HF can ensue as sudden cardiac death (due to the sudden occurence of a ventricular tachyarrhythmia : ventricular tachycardia or ventricular fibrillation), or as a result of end stage HF with worsening heart failure symptoms and fluid overload.
Many of the signs of HF result from sodium and water retention and resolve quickly with diuretic therapy.
Very important for the diagnosis of HF is demonstration of an underlying cardiac cause This is usually myocardial disease causing systolic ventricular dysfunction (for example ischemic cardiomyopathy in the context of a previous myocardial infarction, dilated cardiomyopathy). However, abnormalities of ventricular diastolic function or of the valves (for example severe aortic or mitral valve disease, severe stenosis of the pulmonary valve,etc), pericardium (for example constrictive pericarditis), endocardium, heart rhythm (heart failure due to a tachyarrhythmia), and conduction (heart failure caused by serious bradycardia,advanced atrioventricular block) can also cause HF. Occasionally, more than one abnormality can be present.

Systolic HF, or heart failure with reduced ejection fraction

Systolic HF, or HF with reduced ejection fraction, is due to an impaired left ventricular systolic function: It is a failure of the left ventricle to eject blood in order to maintain a cardiac output adequate to meet the total metabolic needs of the body, under normal ventricular filling pressures. The cardiac output can be reduced (manifestations of inadequate cardiac output are fatigue on exertion, or even hypotension and shock) or more commonly cardiac output may be normal, but under the expense of abnormally elevated ventricular filling pressures, causing the manifestations of congestion (effort dyspnea, nocturnal dyspnea and orthopnea, acute pulmonary edema, pleural effusion, peripheral edema, hepatomegaly, jugular venous distention, etc.). Systolic HF is caused by damage to the cardiac muscle (myocardium) from infarction, inflamation (myocarditis), toxicity (alcohol, chemotherapeutic drugs used for the treatment of malignancies), chronic pressure overload (chronic hypertension, severe aortic valve stenosis), chronic volume overload ( severe aortic or mitral regurgitation, large cardiac shunts due to congenital heart disease), etc.
According to the recent guidelines (ESC 2016) HF with reduced EF is defined by the presence of symptoms and/or signs of HF in patients with left ventricular EF <40 % .

Diastolic HF, or heart failure with preserved ejection fraction (EF)

Diastolic HF, or HF with preserved ejection fraction (EF): However, there is also a large group of patients with signs and symptoms of heart failure, but apparently preserved left ventricular systolic function, with left ventricular ejection fraction ≥ 50%. These patients have diastolic HF, or HF with preserved ejection fraction (EF). The latter term is better, because often patients with this type of HF, do not have a completely normal systolic function, when they are examined with more sensitive tests, such as tissue doppler echocardiogaphy or myocardial strain imaging. These sensitive tests show that these patients usually also have subtle abnormalities of systolic function.  The important fact is, that in these patients the predominant disorder, causing the manifestations of HF, is a disorder of the ventricular diastolic function. In simple words, there is an abnormality in the ability of the left ventricle to fill in diastole, causing elevated filling pressures and manifestations of pulmonary congestion (effort dyspnea, nocturnal dyspnea,orthopnea, even acute pulmonary edema). The severe impairment of diastolic function may be transient (e.g. acute ischemia) or persistent ( e.g. left ventricular hypertrophy due to hypertension, or hypertrophic cardiomyopathy /restrictive or infiltrative cardiomyopathy/ diabetic cardiomyopathy).
Recent guidelines (ESC 2016) define HF with preserved EF by the following criteria:  
(a) Patients with symptoms and /or signs of HF,
(b) left ventricular EF  ≥ 50%, 
(c) elevated natriuretic peptide (BNP> 35 pg/ml or NTProBNP> 125 pg/ml) and
(d) at least one of the following:
Evidence of a relevant structural heart disease (e.g. left ventricular hypertrophy, left atrial enlargement), or
Evidence of diastolic dysfunction (usually obtained with echocardiography).

Heart failure with mid-range EF 

Recent guidelines also define a  form of HF between HF with reduced and HF with preserved EF.  This is:
HF with mid-range EF  and it is defined by the following criteria:
Patients with symptoms and /or signs of HF,
left ventricular EF between 40 and 50 % (41-49%)  plus the criteria (c) and (d) mentioned above for HF with preserved EF.
The symptoms of these patients most propably are caused primarily by mild systolic dysfunction, or by a combination of diastolic and systolic dysfunction.

Stages of heart failure 

This staging classification has been adopted by the guidelines with the purpose to emphasize the progressive nature and the evolution of heart disease leading to the development of HF.

Stage A : People without significant structural heart disease, being at risk for future development of heart failure, based on the presense of risk factors such as hypertension, atherosclerotic disease, diabetes mellitus, prior exposure to cardiotoxic agents (such as doxorubicin), or a family history of a cardiomyopathy. These predisposing factors do not constitute the syndrome of heart failure, so the importance of this stage is to emphasize the need for early identification of individuals with risk factors for a better follow up and for treatment of any modifiable risk factors. 
Stage B includes patients with structural heart disease, but without signs or symptoms of heart failure (HF), such as patients with
previous myocardial infarction, low ejection fraction (EF), left ventricular hypertrophy, or asymptomatic valvular disease.
Patients with asymptomatic left ventricular systolic dysfunction (of ischemic or non ischemic etiology) should receive an ACE inhibitor to reduce of developing symptomatic heart failure and death. If there is intolerance to an ACE- inh because of cough or angioedema, an angiotensin receptor blocker- ARB( especially valsartan) is an effective treatment alternative. In patients with left ventricular dysfunction in the context of a myocardial infarction, the combination of an ACE inhibitor and ARB is not better than either alone, so in this setting combination therapy is not recommended.  
Beta -blockers in patients with a recent myocardial infarction and reduced left ventricular EF (≤40%) also improve survival and reduce subsequent nonfatal myocardial infarctions,when added to an ACE inhibitor.
Stage C:  Patients with structural heart disease with prior or current symptoms of HF (e.g. shortness of breath, fatigue, reduced exercise tolerance, edema)
Usual treatment includes diuretics for fluid retention (symptoms and signs of congestion) and for patients with stage C heart failure with reduced left ventricular EF drug cate proven by randomized trials to reduce mortality (and also reduce hospitalizations) :  ACE inhibitors (or ARBs) beta- blockers, mineralocorticoid antagonists. (See below the chapter on treatment and the links to the guidelines).
Stage D
Refractory HF requiring specialized interventions. This stage includes patients with marked symptoms at rest, despite maximal medical therapy (e.g., those who are recurrently hospitalized for HF symptoms). Besides optimal medical treatment, with the drugs used for stage C, these patients often require treatment in specialized centers and for some of them advanced forms of treatment are required (such as chronic-permanent mechanical circulatory assist devices, heart transplantation, treatment with intravenous inotropic medications).

The NYHA classification of  heart failure (HF) 

The New York Heart Association (NYHA) classification is a scale used for classifying patients with HF according to the severity of symptoms and has prognostic and therapeutic implications:
 NYHA I: asymptomatic 
NYHA II: symptomatic with moderate exertion 
NYHA III: symptomatic with mild exertion and may limit activities of daily living
NYHA IV: symptomatic at rest.

A practical clinical classification of patients with heart failure

Is it possible to classify patients with heart failure (HF), especially those with acute HF, into hemodynamic categories according to their clinical manifestations, and can this influence the treatment strategy ?
Yes...The manifestations (signs and symptoms) of HF can be classified into those caused by low perfusion (i.e., "cool" hemodynamics) and those caused by congenstion (increased pulmonary and systemic venous pressure and salt and water retention = "wet hemodynamics"). 
The manifestations of low perfusion (decreased cardiac output=is decreased volume of blood passing through the circulation per minute) are the following: 
Decreased pulse pressure (pulse pressure =  systolic pressure –diastolic pressure), cool extremities, altered mental status and decreased urine output. Some or all of these manifestations can be present depending on the severity of the patient's condition.
The manifestaitons of congestion (i.e., wet hemodynamics) can be some or all of the following :
 Dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, edema, elevated jugular venous pressure (external jugular veins become distended and the pulsations of the internal jugular vein are visible at an increased height, measured from the sternal angle), ascites (abdomimal distention due to the accumulation of fluid), an audible third heart sound  at early diastole, crackles on lung auscultation, hepatojugular reflux.
A practical, simplified, approach is to classify the patient with HF into one of the following hemodynamic profiles: 
 Warm and dry: the patient is well compensated, with no manifestations of low tissue perfusion or congestion. No change in medical management is needed on the basis of the clinical manifestations.
 Warm and wet: The patient is congested but has no manifestations of decreased perfusion. Diuretic treatment should be increased to reduce congestion.
 Cool and dry: The patient has manifestations of diminished perfusion, but no manifestations of congestion. A general rule is to add inotropic support to improve perfusion, especially if the manifestations are severe, but also the dosage of vasodilators such as ACE inhibitors can be increased (with caution to avoid hypotension), in order to reduce afterload and hence increase cardiac output. 
Cool and wet: The patient has manifestations of diminished perfusion as well as manifestations of congestion. A general rule is to increase diuretic therapy, to treat congestion and add inotropic support (especially if the patient has severe signs of diminished perfusion, or significant hypotension).
The above classification is simplified and schematic, but it is often helpful, especially in some cases of acute heart failure. We should emphasize that the cornerstone of the treatment of HF with reduced EF (systolic HF) is formed by those medications proved in major clinical trials to increase survival: angiotensin converting enzyme inhibitors (ACE-inhibitors) or angiotensin receptor blockers (ARBs),  beta-blockers and aldosterone antagonists.

Imaging in heart failure ( Chest radiography / Echocardiography)

The chest x -ray is a simple and widely available imaging study that can provide some important clues, but the most useful study in a patient with suspected or known HF is echocardiography.

The chest X-ray of a male patient, 60  years old, ex-smoker (15 pack-years), with no history of increased alcohol consumption and with no previous history of cardiac or respiratory disease. He presented with effort dyspnea  class NYHA-3 in the last 2 months and a general feeling of tiredness. The physical examination revealed no significant findings, other than reduced intensity of heart sounds. Auscultation of the lungs was also normal. Is the shortness of breath most probably due to a cardiac or a respiratory disorder?  What further testing is indicated ?

Findings include enlargement of the hilar shadows, dilatation of the lung vessels and more prominent vascular markings in the upper lung fields. These are signs suggestive of elevated pulmonary venous pressure due to heart disease. In contrast there are no findings  indicative of a pulmonary disease. Increased dimensions of the cardiac shadow are also observed with increased prominence of the lower portion of its left margin. The latter finding suggests dilatation of the left ventricle (LV). These findings in conjunction with the presenting  symptom of effort dyspnea favor the diagnosis of heart failure (HF), the cause and the severity of which can be investigated by means of further  tests. An ECG and an echocardiogram are absolutely mandatory. According to the ESC guidelines (2016) the following laboratory tests are recommended for  a patient with newly diagnosed HF in order to evaluate the patient’s suitability for particular therapies and to detect treatable causes and comorbidities: Hemoglobin and WBC - 
urea, creatinine (with estimated GFR), sodium, potassium,  - glucose, HbA1c --lipid profile- liver function tests (AST, ALT, bilirubin,GGT)  TSH - ferritin. Natriuretic peptides can also be cosidered as a part of the evaluation. Depending on the findings and the pretest probability of coronary artery disease (risk factors), coronary angiography is often indicated in cases of HF, especially with LV systolic dysfunction, to confirm or exclude coronary artery disease, as a common underlying cause.
On echocardiography this patient  had a dilated and diffusely hypokinetic LV with an EF 35 % and also a dilated left atrium. The right heart chambers and the valves were without significant abnormalities (appart from moderate functional mitral regurgitation). Coronary angiography did not reveal significant coronary arterial stenoses. He was diagnosed with HFrEF due to dilated cardiomyopathy and treated with an ACE inhibitor (quinapril), a beta blocker (carvedilol), an MRA (eplerenone) and a loop diuretic (furosemide). Symptoms resolved and on re-evaluation after three months of treatment his EF had improved (40 %) and the dilatation of the LV had decreased. Subsequently, the dosage of the diuretic was reduced and the dosage of the ACE inhibitor was increased.

A reminder of relevant chest X ray anatomy

In the posteroanterior chest radiograph the right border of the cardiomediastinal shadow is formed (from its lower to its upper parts), by the right atrium, the ascending aorta, and superior vena cava and further cranially it widens into a funnel shape, where its right border is formed by the brachiocephalic trunk. The upper margin of the left cardiomediastinal silhouette (from its upper to its lower portions) is formed by the aortic arch, the left pulmonary artery and the atrial appendage. The lower part of the left cardiomediastinal silhouette is formed by the left ventricle. The contour of the left hemidiaphragm is visible through the heart shadow almost as far as the shadow of the vertebral column.
Lateral chest x ray: The anterior cardiac border is formed by the right ventricle. and its upper part by the shadow of the aortic root continuing to the shadow of the aortic arch. The anterior surface of the right ventricle normally is in contact with the sternum along less than one-third of the length of the sternum 
The cranial border of the middle mediastinum is defined by the shadow of the aortic arch. The shadow of the arch is interrupted by the radiolucent (black) band of the trachea and main bronchi. The lower part of the posterior heart border is formed by the left ventricle and its upper part by the left atrium.

Chest radiography in heart failure:

It is indicated for patients with suspected new-onset HF or with worsening HF. The goal is to assess heart size and to detect signs of pulmonary congestion, as well as to search for a possible pulmonary disease that may cause or contribute to the patient’s symptoms.
A usual finding in patients with HF with reduced EF is an enlarged cardiac silhouette (cardiomegaly): In an inspiratory posteroanterior chest x ray the width if the cardiac silhouette is more than half of the width of the maximum internal diameter of the thorax. Cardiomegaly is almost always present in chronic systolic HF. In some forms of acute-new onset systolic HF, such as in the context of an acute myocardial infarction, cardiomegally often is not present (because the left ventricle did not have time to dilate), but there are signs of pulmonary congestion. 
Clear signs of pulmonary congestion (elevated pulmonary venous pressure) are usually present in acute heart failure, but in much fewer patients with chronic heart failure. Such signs are
 Upper lobe redistribution (enlarged upper lobe vessels in comparison to lower lobe vessels-in other words:prominence of upper lobe blood vessels. Normally, on the erect radiograph upper lobe vessels are less prominent and have a smaller diameter than lower lobe vessels.Important:The term redistribution applies to chest x-rays taken in full inspiration in the erect position),  
Enlarged hilar shadows of the lungs (due to dilated pulmonary veins) and increased diameter of the pulmonary vessels, 
Septal or Kerley B lines
[These lines-named after Peter Kerley, a radiologist from Ireland- are short,
 usually 1 -2 cm in length, parallel horizontal  thin lines at the lung periphery,They represent thickened interlobular septa (because of interstitial edema, i.e increased interstitial fluid).They are parallel to one another, at right angles to the pleura. kerley B lines may be seen in any lung zone, but usually they are observed at the bases on the PA radiograph, and in the substernal region on lateral radiographs. The usual cause of Kerley B lines is interstitial pulmonary edema from  congestive heart failure,. There are also other causes that can produce Kerley B lines by thickening of the septa between pulmonary lobules, such as pulmonary fibrosis, pneumoconiosis, lymphangitis carcinomatosa, malignant lymphoma, viral and mycoplasmal pneumonia.]
When fluid leaks into the peribronchovascular interstitium it is seen as thickening of the bronchial walls (peribronchial cuffing) and as loss of definition of hilar vessels (perihilar haze). Τhe above signs (Kerley B lines, peribronchial cuffing and perihilar haze) are signs of interstitial pulmonary edema (leakage of fluid into the interstitium of the lungs).and in more severe cases of congestion: 
Alveolar pulmonary edema, due to leakage of fluid into the alveoli : Alveolar pulmonary edema is characterized by perihilar consolidations, i.e.large shadows or infiltrates (white areas like mist) surrounding the pulmonary hilae and air bronchograms within these consolidations. Air bronchogram is the appearance of air-containing bronchi within an area of consolidation, as branching radiolucent (=black) lines. 
Pleural effusions are not rare in HF, often bilateral. In HF when there is a unilateral pleural effusion, it is usually on the right side.

Echocardiography: Useful indices of left ventricular systolic function

M-mode echocardiography, which records the motion of cardiac structures in one dimension, can be used to obtain some indices of left ventricular (LV) systolic function. Measurements of LV dimensions are made in the parasternal long-axis view by positioning the cursor through the LV minor axis at the level of the tips of the mitral leaflets. Then fractional shortening (FS) can be calculated and even ejection fraction (EF) can be calculated  with geometric assumptions (that are not accurate, if there are significant differences in regional contractile function, between various segments of the LV walls).

Fractional shortening (FS) is calculated from linear measurements

of LV dimensions from M-mode or 2D images:

FS = 100% × (LVDd – LVDs)/LVDd 

where LVDd and LVDs are the LV end-diastolic dimension and

end-systolic dimension, respectively. FS normal values : 25-45 %
FS as an index of global LV function can be problematic when there is a marked difference in regional function, in patients with a previous myocardial infarction.

Two-dimensional (2D) echocardiography for the evaluation of LV systolic function

This is the primary mode for evaluation of LV systolic function. Endocardial border
motion and wall thickening can be visualized and an experienced examiner can assess regional and global contractile function and roughly estimate the ejection fraction (EF) just by visualizing the LV in various echocardiographic views ("eyeball approach"). Quantitative measurements are obtained by tracing the endocardial border in end diastole and end systole in the apical 4- and 2-chamber views  using the method of discs (modified Simpson rule). The machine software divides the LV along its long axis into a series of
discs of equal height. Individual disc volume is calculated as
height x disc area. LV volume is then calculated as the sum of disc volumes.
The ejection fraction (EF)= stroke volume/end diastolic volume.
Stroke volume= the volume of blood ejected by a ventricle in systole= EDV-ESV. 

(EDV= end diastolic volume, ESV= end systolic volume). Thus 
The left ventricular EF generally has a normal value   55%. It is a measure of global LV systolic function, with established prognostic significance (the lower the EF, the worse the prognosis), but it is also influenced by preload, afterload, heart rate, and valvular function. Left ventricular EF is a strong predictor of clinical outcome and is widely used to make clinical decisions.
EF should be calculated from volumetric measurements
by 2D echocardiography. Even more accurate measurements of left ventricular volumes and EF are obtained with three dimensional (3D) echocardiography, or magnetic resonance imaging (MRI). The latter two techniques have similar accuracy.

Doppler Echocardiography derived systolic indices (stroke volume)

Doppler echocardiography also provides some indices of LV systolic function, such as the stroke volume (SV), i.e. the blood volume ejected per beat. For this measurement one obtains from the apical 5 chamber view the pulse wave doppler signal of the velocity in the left ventricular outflow tract (LVOT) and also measures the diameter of the LVOT (in the parasternal long axis view at the base of the aortic valve leaflets or immediately proximal to the aortic valve).  
SV= VTI (LVOT) x area (LVOT)
VTI is the velocity time integral (also named time velocity integral-TVI) of blood flow through the LVOT during systole. 
This formula is explained as follows: VTI is calculated as the area under the curve of the doppler velocity signal (which displays velocity on the vertical axis and time on the horizontal axis). This area of the doppler signal is automatically calculated by the machine software, after the examiner manually traces the doppler velocity signal. It mathematically represents a velocity time integral, i.e. the sum of many products of velocity x time, each corresponding to every small time interval in systole. Since in every small time interval the column of blood moves by a distance given by the product of blood velocity x time interval, the VTI as a sum represents the total distance the column of blood has "traveled" in systole. This distance multiplied by the area of the orifice through which blood has passed, is the volume of blood which passed through the orifice in systole= the stroke volume (SV).  Assuming a circular LVOT with radius r and diameter D (=2r) : 
LVOT area = πr2=3,14r2=3,14(D/2)2 = (3,14 D2)/4= 0,785D2 
In the absense of aortic regurgitation, SV reflects the forward effective blood flow in a cardiac beat and multipied by heart rate (beats per minute) it gives the cardiac output (= the volume of blood passing through the circulation per minute). Strictly speaking, the SV is the hemodynamic result of LV function and not a true index of systolic function. Normal values of SV: 55-100 mL.

Tissue Doppler Imaging (TDI)

 Measurement of mitral ring velocities or myocardial velocities of the basal segments (velocity of the movement of these tissues along the longitudinal axis of the heart) is a simple and sensitive method for the assessment of the left ventricular systolic and diastolic function. Both peak systolic (Sm) and early diastolic (Em) mitral annular or left ventricular basal velocities are nearly always reduced in patients presenting with the clinical syndrome of systolic heart failure.
The systolic annular velocity of the mitral valve (Sm) generally correlates well with the left ventricular EF. Normally Sm is >7.5 cm/sec,
 when it is measured with pulse wave tissue doppler (PW-TDI). Note that myocardial velocities measured by the color TDI method are lower than velocities by pulsed Doppler (typically about 25% lower).
The Sm is also a sensitive marker of mildly impaired left ventricular systolic function, even in people with apparently preserved systolic function and a normal EF, for example in those with diastolic heart failure, or in diabetics without overt heart disease. Reduced annular TDI velocities are also present in subjects with hypertrophic cardiomyopathy, (even in people having the related gene mutations, who are at the stage of subclinical disease, with no cardiac hypertrophy).

Myocardial strain and strain rate imaging

In general, in myocardial segments with diminished systolic function, systolic velocities are typically reduced and there are also reductions in systolic strain and strain rate. Strain is the proportion (percentage) of change in length of the myocardium (units %) and it is negative in systole, since there is a negative change in length (shortening), and positive in diastole (because in diastole the length increases).
 Strain = L-Lo /Lo , where L is the current length and Lo is the original length of a myocardial segment. Strain rate (SR) is the rate of change of the strain value= the proportional change in length per unit of time. SR units are s-1

SR is negative in systole (because it represents the rate of proportional decrease in myocardial length) and positive in diastole (because it represents the rate of increase in length). LV longitudinal velocities measured from an apical window increase progressively from the apical toward the basal myocardial segments. Longitudinal strain and strain rate, however, are essentially similar between apical and basal segments.
The normal value of the peak systolic strain (percentage of shortening) of the left ventricle during systole in the longitudinal axis is greater than 15%. To be more accurate, lets mention that normal  peak systolic strain has a value  more negative than  -15%, usually between -15 and -25%. (The negative sign indicates a decrease in the length of the myocardium, i.e. shortening).
Peak systolic strain is influenced by preload (like the ejection fraction which is also influenced by the ventricular loading conditions) and can be used as an indicator of the total, and of the regional systolic function (when measured at a segment of the left ventricle). 
The normal value for the peak systolic strain rate of the left ventricular myocardium is between  - 1.2  and  - 2  s-1 (sec-1=1/s).
 In normal hearts the value of strain rate and strain is about the same in all myocardial segments from the base to the apex of the heart, (showing no significant difference). Conversely, myocardial velocity recorded by the tissue Doppler (in cm/s), and the displacement (change in position) of a given point of the myocardium (in mm) is greater in the basal portions and is getting smaller towards the apex.
An advantage of the percentage of myocardial deformation (strain) and of the rate of the proportional change in deformation (strain rate) is the following: Strain and strain rate is not affected by translational motion of the heart ("bouncing" movements in the chest during systole). In contrast, the myocardial velocities recorded with tissue Doppler (TDI) are affected by the translational motion of the heart within the chest and not only by the motion of myocardial shortening in systole or lengthening in diastole.
A diminished peak systolic strain, or strain rate is a sensitive marker of an impairment in systolic function.
Need more information about these modern echocardiographic techniques ? In that case, here is a link for you to click on (free review article with option to download PDF) ...

Strain and Strain Rate Imaging by Echocardiography – Basic Concepts and Clinical Applicability

Dandel Μ ,Lehmkuhl H, et al. Strain and Strain Rate Imaging by Echocardiography – Basic Concepts and Clinical Applicability. Current Cardiology Reviews, 2009, 5, 133-148. 

Treatment of systolic heart failure (HF with reduced ejection fraction)

The first step in the treatment of heart failure (HF) with reduced EF usually is starting three medications (an ACE-inhibitor, or an ARB, a beta blocker and a diuretic-see below). The diuretic is indicated if there are signs or symptoms of congestion, because it reduces symptoms, improves exercise tolerance and reduces the risk of hospitalization for HF. The ACE-inhibitor and the beta blocker are very important because they reduce mortality and the risk of HF hospitalization. ARBs are recommended only as an alternative (instead of an ACE inhibitor), in patients intolerant of an ACE-inhibitor.
Important: In every patient with ejection fraction (EF) ≤ 40 % there is a class I indication (i.e. a "strong and clear" indication) for treatment with an ACE-inhibitor, (or an ARB, if the first is not well tolerated) and a beta blocker, because this treatment reduces mortality (rates of death) and the rate of hospitalizations for HF. 
 Diuretics are clearly indicated in parients with HF (systolic or diastolic) if they have symptoms or signs of congestion and provide improvement of symptoms. They have not been shown in trials to reduce mortality.
Angiotensin converting enzyme (ACE)  inhibitors are first line drugs in systolic heart failure (heart failure with reduced EF). ACE-inhibitors prevent conversion of angiotensin I to angiotensin II. This results in lower systemic vascular resistance (since angiotensin II induces vasoconstriction) and less secretion of aldosterone. Use of ACE inhibitors in patients with HFrEF increases survival, improves symptoms, decreases hospitalizations and improves left ventricular systolic function (the EF). 
An Angiotensin receptor blocker (ARB) can be given instead, if the ACE inhibitor is not well tolerated by the patient. ARBs are specific antagonists to the angiotensin II type 1 receptors and so they act by inhibiting the effects of angiotensin II.
Absolute contraindications for an an ACE inhibitor or an ARB include pregnancy and bilateral renal artery stenosis. An absolute contraindication for an ACE inhibitor (and relative contraindication for an ARB) is a history of angioedema. 
When using an ACE-inh or an ARB, caution is required in hyperkalemia (these drugs can cause elevation of potasium levels), in hepatic impairment, in renal dysfunction or unilateral stenosis of the renal artery (in this case there is a risk of causing deterioration of renal function), in aortic or mitral valve stenosis (risk of causing hypotension-if treament with these drugs is needed, one must be cautious to avoid rapid dose increments).
 Relative contraindications for an ACE inhibitor or an ARB  include hypotension (systolic blood pressure < 90 mm Hg), hyperkalemia (potassium > 5.5 mEq/L), severe renal insufficiency (creatinine > 3.0 mg/dL). 
Unique side effects of ACE inhibitors are cough and angioedema. Chronic nonproductive cough associated with ACE inhibitors is caused by elevated levels of bradykinin. All attempts should be made to identify an alternative cause of cough before discontinuing the ACE inhibitor and replacing it with an ARB. 
Angioedema is a rare complication of ACE inhibitors (0.4%) manifested by soft tissue edema of the lips, face, tongue, and, occasionally, the oro- pharynx and epiglottis. This rare complication typically begins in the first 2 weeks of ACE inhibitor therapy, but in some patients it presents months to years after starting therapy.
ARBs are used and monitored in the same manner as ACE inhibitors. ARBs have a similar side-effect profile to ACE inhibitors (e.g.they can induce hypotension, or occasionally they can induce renal insufficiency and hyperkalemia in some patients), but unlike ACE-inhibitors, ARBs do not induce cough and angioedema is a much more rare side effect with ARBs than with ACE inhibitors. Among ARBs, the best studied  in patients with heart failure are valsartan and candesartan and they should be preferred.

A beta blocker (carvedilol, bisoprolol, or metoprolol sustained release tablets, or nebivolol) is initiated with a low dose. 
The dosage of ACE inhibitor or ARB and beta-blocker (starting from a low dosage) should be gradually titrated to the evidence-based dose, used in the major trials, or to the maximum tolerated dose below the evidence based dose. 
Thus, in a symptomatic patient (NYHA II-IV) with HF with reduced left ventricular ejection fraction (EF<40%) according to the current guidelines (ESC-2016) initial treatment must include an ACE inh (or an ARB), a beta blocker and if there are  symptoms or signs of congestion a diuretic (usually loop diuretic, e.g. furosemide). 
 The dose of the ACE inh (or ARB) and of the beta blocker should be gradually increased (up-titrated) to reach the evidence based dosage, or the maximum tolerated dosage below the evience based dosage. If the patient becomes asymptomatic no further medications are added (and we can consider reducing the diuretic dose). 
If a patient with HF with reduced LVEF remains symptomatic (has symptoms NYHA II-IV) despite the above therapy with an ACE-inh and a beta blocker, then there is a clear indication to add a mineralocorticoid receptor antagonist (MRA). Thus, in this case treatment includes ACE-inh+beta blocker+MRA (+diuretic for symptoms or signs of congestion). 
To summarize the indication of an MRA as mentioned in the guidelines : For patients who remain symptomatic (NYHA class II-IV) under treatment with diuretic+ACE inh. (or ARB) + beta blocker and also have an EF ≤ 35 %, a mineralocorticoid receptor antagonist (MRA) is added to this treatment scheme. 
MRAs (spironolactone and eplerenone) are aldosterone antagonists, i.e. they prevent aldosterone from binding to its receptors. In such patients they reduce mortality and hospitalizations for HF.
Contraindications of aldosterone receptor antagonists (MRAs): potassium> 5 mmol / lt before the initiation of treatment, or severe renal failure:  creatinine ≥2,5 mg / dL ,or calculated creatinine clearance ≤30 mL / min / 1,73 m2 body surface area.
 For patients with EF ≤ 40% who remain symptomatic on treatment with a beta blocker, an ACE-inh. and a diuretic, if they cannot tolerate an MRA (or if this drug is contraindicated) an ARB can be added instead of the MRA and so treatment will include a beta blocker, an ACE-inh and an ARB (and a diuretic). 
For patients with EF ≤ 40 % who cannot tolerate an ACE inh. because of cough, the treatment should include a beta blocker plus an ARB plus an MRA.
Note : A combination of three drugs blocking the renin-angiotensin-aldosterone axis, i.e. an ACE-inh plus an ARB plus an MRA should never be used, due to adverse effects.
For patients with systolic HF who remain symptomatic despite the above treatment (including a beta blocker, an ACE-inh or ARB, an MRA and a diuretic = 4 drugs) , if LVEF is ≤ 35 % and the patient can tolerate an ACE-inh or an ARB, then there is an indication to replace the ACE inh or ARB used in the above drug regimen with a new drug : ARNI (angiotensin receptor neprilysin inhibitor). Thus treatment includes then : beta blocker+ diuretic+ARNI+ MRA. ARNI is a new therapeutic class acting on the renin -angiotensin-aldosterone system (RAAS) and the neutral endopeptidase system.  The first drug in this class is LCZ696, a molecule that combines the moieties of valsartan and sacubitril in a single substance. Sacubitril is a  neprilysin inhibitor. By inhibiting neprilysin, the degradation of netriuretic peptides, bradykinin and other peptides is slowed and this has beneficial effects in the course of systolic HF, because natriuretic peptides enhance diuresis, natriuresis and myocardial relaxation, reduce the progress of adverse LV remodelling and inhibit renin and aldosterone secretion. 
Contraindications and precautions regarding the use of ARNI (LCZ696)
 Concomitant treatment with an ACE-inh , or an ARB is contraindicated. Coadministration with direct renin inhibitor (aliskiren) is also not recommended.
Contraindications include: 
Hypersensitivity (allergy) to the active substance or ingredients 
Second and third trimesters of pregnancy 
History of angioedema related to a previous treatment with an ACE inhibitor or an ARB, or history of hereditary or idiopathic angioedema
 Severe hepatic dysfunction or cholestasis
Treatment onset with ARNI should be at least 36 hours after discontinuation of treatment with ACE-inh (due to the potential risk of angioedema).

The addition of ivabradine to the above treatment is indicated to reduce hospitalization rates in patients with EF≤ 35 %, in sinus rhythm with heart rate ≥ 70 beats /minute who remain symptomatic, despite the above drug combination (including an evidence based ,or maximum tolerated dose of a beta-blocker combined with 2 inhibitory drugs of the renin-angiotensin-aldosterone axis: an ACE-inh or an ARB or ARNI plus an MRA / or an ACE inh plus an ARB). Ivabradine has an indication of class IIa.

Digoxin may be considered (indication of class IIb) to reduce the risk of HF hospitalization in patients  with an EF ≤ 45% : 1) in sinus rhythm who are unable to tolerate a beta-blocker (ivabradine is an alternative in patients with symptomatic HF with reduced LVEF unable to tolerate a beta- blocker and sinus rate ≥70/min.), or 2) with persisting symptoms despite optimal treatment (with the above medications) or with atrial fibrilation and inadequately controlled ventricular response (ventricular rate).

Cardiac resynchronization treatment (CRT)

i.e. the implantation of a biventricular pacemaker is generally  recommended for patients with symptomatic systolic HF (despite optimal medical treatment), with  a  QRS duration is  ≥ 130 ms (miliseconds) and left ventricular ejection fraction LVEF≤ 35%. 
 It is not recommended for patients with a QRS duration < 130 ms.
The specific indications are as follows: CRT is recommended for symptomatic patients with HF in sinus rhythm with a QRS duration  ≥ 130 ms and left bundle branch block (LBBB) and with LVEF ≤35% despite optimal medical treatment (a class I indication). 
In patients with systolic HF, (HFrEF) with  LVEF≤ 35% and symptoms despite optimal medical treatment : CRT should/may be considered (class II indication) if :
 QRS ≥ 130 msec with non-LBBB in sinus rhythm, or 
for patients in AF and  QRS ≥ 130 msec with NYHA Class III–IV provided there is a strategy to ensure bi-ventricular capture, or the patient is expected to return to sinus rhythm.

CRT in patients with the above characteristics has been shown in trials to improve symptoms and reduce morbidity and mortality.   Biventricular pacing (CRT) rather than right ventricular pacing is recommended for patients with systolic heart failure (HFrEF) regardless of NYHA class with an indication for ventricular pacing, because of high degree AV block in order to reduce morbidity. This also includes patients with AF.

Indications for an implantable cardioverter-defibrillator (ICD) in patients with heart failure 

to reduce the risk of sudden death and imrove survival are the following:
Primary prevention : In symptomatic patients (NYHA class II-III) with systolic HF an implantable cardioverter-defibrillator (ICD) is indicated if  LVEF≤ 35%, despite ≥3 months of optimal medical treatment provided they are expected to survive longer than one year with good functional status. This indication is for sympomatic patients with EF≤ 35% who have: 
a) ischemic heart disease but they did not have a myocardial infarction in the prior 40 days or 
b) dilated cardiomyopathy DCM.
ICD implantation is not recommended in patients with HFrEF in NYHA class IV with severe symptoms refractory to pharmacological therapy because these patients will not have a survival benefit. Exceptions to this rule are patients with HFrEF class NYHA IV who are candidates for a treatment cabable of improving the course of their end stage HF, such as cardiac resynchronization treatment (CRT), a ventricular assist device, or cardiac transplantation. 
For secondary prevention : If the patient has recovered after an episode of ventricular arrhythmia causing haemodynamic instability (ventricular tachycardia, or ventricular fibrillation) not due to an identifiable reversible cause and  expected to survive for >1 year with good functional status.
An ICD in asymptomatic patients with systolic HF (HFrEF)  is recommended in patients receiving optimal medical treatment with severe systolic dysfunction : LVEF ≤30%  either of ischemic origin, who are at least 40 days after acute myocardial infarction, or of non-ischemic origin (with asymptomatic non-ischemic dilated cardiomyopathy).ICD is recommended in patients: a) with asymptomatic. 
 In patients with the above indications randomized controled trials have shown that an ICD prevents sudden death and prolonsg life.
As mentioned above, since the implantation of an ICD aims to increase survival, it is considered in the absence of other diseases likely to cause death within the following year.
Patients with systolic HF, with one of the above indications for ICD implantation, if they have οn the ECG a QRS duration ≥130 ms should be considered for a defibrillator with biventricular pacing, i.e. with cardiac resynchronization treatment (CRT-D= cardiac resynchronization treatment and defibrillator) rather than ICD.

Treatment of Heart Failure with preserved ejection fraction (HFpEF) and of  Heart Failure with middle range ejection fraction (HFmrEF)

Diuretics are recommended in patients with HFpEF or HFmrEF, who have symptoms or signs of congestion. They are effective in alleviating symptoms. A study has also shown improvement in NYHA class with candesartan.
Patients with HFpEF or HFmrEF should be screened for both cardiovascular and noncardiovascular comorbidities, which, if present, should be treated in order to improve symptoms, well-being and/or prognosis. For example these patients often have hypertension, diabetes mellitus, or coronary artery disease. These conditions, which are also known to cause diastolic dysfunction, should be diagnosed, their severity should be assessed and effectively treated. Coronary reperfusion should be considered if there is  symptomatic coronary heart disease (angina), or in cases where significant ischemia is demonstrated by non invasive diagnostic tests, if ischemia is considered to be involved in symptom worsening.
An important note is that no treatment has yet been shown convincingly, to reduce mortality in patients with HFpEF or HFmrEF. Trials of ACE-inhs, ARBs, beta-blockers and MRAs have failed to show mortality reduction in patients with HFpEF or HFmrEF. However, there is an exception to that general rule : Nebivolol in older patients with HFrEF, HFpEF or HFmrEF,  reduced the combined endpoint of death or cardiovascular hospitalization,with no significant association between treatment effect and left ventricular EF.
Patients with diastolic LV dysfunction often deteriorate in case of a tachycardia or tachyarrhythmia (because the duration of diastole is reduced). Then control of heart rate  (eg with beta-blockers or diltiazem) or restoration of normal sinus rhythm (when possible) is an important aspect of treatment.

Other treatment options for severe acute decompensated or chronic end stage heart failure with reduced EF.

Ventricular assist devices (VADs) 

These devices are used for patients with acutely decompensated heart failure (HF) not responding to medical treatment and also for end stage (ie, ACC/AHA stage D) chronic HF. The left ventricle can be supported with a left ventricular assist device (LVAD), the right ventricle with a right ventricular assist device (RVAD), or both ventricles with a biventricular assist device (BiVAD). Another term for a VAD is a ventricular assist system (VAS).
A LVAD can be placed temporarily in acute refractory left ventricular failure (for example in patients acute, severe myocarditis) as a bridge to recovery. This can be achieved by unloading the dysfunctional heart to allow reverse remodeling ,ie reduction of the left ventricular (LV) dilatation and improvement in systolic function)  
A VAD can also be used in patients with end-stage heart failure, either as a bridge to heart transplantation, or for long term destination (permanent) treatment, especially in patients with severe heart failure who are not transplant candidates and who otherwise would die without treatment.. 
For patients with end stage HF, destination therapy with LVADs compared to medical therapy has shown better results (than medical therapy) in terms of quality of life and longer survival. This has been shown in the REMATCH trial (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) and also confirmed by newer data.
Potential complications of ventricular assist devices (VADs)
Although VADs improve survival and quality of life in patients with end stage HF, complications can occur and patients need expert follow up. Potential complications include mechanical dysfunction, infection, bleeding, and thromboembolic events. .

For a detailed analysis of the management of HF, please use the links to heart failure-guidelines given at the bottom of this page. 

Heart failure and heart disorders due to chemotherapy (cardio-oncology)

This is one of the possible causes of heart failure or left ventricular dysfuction, that often require evaluation from a cardiologist. The major causes of chemotherapy-induced cardiomyopathy are the anthracyclines, daunorubicin and doxorubicin. 
Anthracycline chemotherapeutics and mitoxantrone (a chemically similar antineoplastic medication) can cause irreversible dilated cardiomyopathy that is related to cumulative dose. The dilated cardiomyopathy,induced by these drugs should be treated with the usual therapy for congestive heart failure. Myocyte injury may occur early after anthracycline exposure ( according to data from endomyocardial biopsy and troponin I measurements). However, clinical manifestation occasionaly may not become apparent until months to years after drug exposure due to cardiac
reserves and the activation of compensatory mechanisms. 
The probability of cardiomyopathy due to antracyclines is dependent on the cumulative dose of medication: the risk of cardiomyopathy is less than 1% at a dose < 400 mg/m  of body surface area, but more than 15% at 700 mg/m 2 .
Factors increasing the risk of cardiomyopathy include age >70, preexisting cardiac disease, concomitant use of cyclophosphamide and previous chest irradiation.
Early cardiac side effects, when they occur, are typically reversible and self-limiting and include dysrhythmia, repolarization changes in the ECG, pericarditis, and less frequently myocarditis. However, with a higher cumulative dose irreversible dilated cardiomyopathy can occur.
Because anthracycline chemotherapy can cause left ventricular systolic dysfunction, before beginning such chemotherapy, all patients should have an initial evaluation of ventricular function by echocardiography.
Chemotherapy should not be initiated if the ejection fraction (EF) is
< 30%, but it may be administered to patients with high-risk malignancies and an EF 30%-50%.
 If EF is 50% or more, the risk of cardiomyopathy is low. However, the EF should be assessed again after dose levels of 300 mg/m and 400 mg/m  and after each subsequent dose.
Discontinuation of chemotherapy is indicated if the EF decreases from baseline by 10% or more, or if the EF decreases to less than 50%, in patients who previously had a normal EF.

Anthracyclines and mitoxandrone may also cause acute toxicity, characterized by ECG changes: QT interval prolongation and nonspecific ST-segment and T- wave changes.  
Other drugs used for the treatment of malignant disease (cancer etc) that can cause cardiotoxicity are the following:
The second most common cause of cardiotoxicity (next to anthracyclines) among these drugs is fluorouracil. It can induce coronary vasospasm, resulting in angina or myocardial infarction. It can also cause myocarditis, or arrhythmia.
Trastuzumab (Herceptin), used in the treatment of breast cancer can cause reversible cardiomyopathy with reduced ejection fraction (EF). The risk of heart failure during treatment with trastuzumab as adjuvant therapy is approximately 5%, but may reach 25% in combination with anthracyclines.
Cyclophosphamide in high doses can induce acute cardiomyopathy ( a dilated cardiomyopathy similar to that induced by anthracyclines, with similar treatment) or hemorrhagic myopericarditis. This toxic effect is not related to the cumulative dose. 
Paclitaxel can cause heart block or it may result in cardiomyopathy when combined with an anthracycline.

 The best strategy for treatment and prevention of further deterioration of cardiomyopathyi nduced by chemotherapy is withdrawal of cardiotoxic drugs or use of fewer cardiotoxic agents. This should always be balanced against the need to treat the malignant disease. A few studies suggest that treatment with ACE- inhibitors, angiotensin II receptor blockers, or beta-blockers as a single-drug therapy may protect against chemotherapy-induced cardiomyopathy. The beta-blocker carvedilol may exert its protective effect in part through a potent antioxidant effect, thus targeting one of the mechanisms of anthracycline-induced cardiomyopathy. A combined preventive treatment of patients receiving intensive chemotherapy for hematologic malignancies ACE- inhibitor (enalapril), plus a beta-blocker (carvedilol) can reduce the detrimental effects of this treatment in LV ejection fraction,(as shown in a small study, the OVERCOME trial). Furthermore, the extensive documentation that the combination an ACE- inhibitior and a beta-blocker can markedly reduce mortality in the general heart failure population suggests that this strategy should be used, but also further tested,  during cancer therapy.
Current guidelines state that treatment of chemotherapy-induced heart failure should follow the same principles as in treating heart failure due to other cardiomyopathies.The current main strategy is to stop ongoing chemotherapy with cardiotoxic drugs, to avoid further use of anthracyclines and administer to the patient traditional heart failure therapy. There are still unresolved issues, such as the question: "what degree of heart dysfunction, or heart failure, is acceptable as a prize for the cure of a malignant disease?"

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

Smiseth O, et al. Cardioprotection During Chemotherapy Need for Faster Transfer of Knowledge From Cardiology to Oncology and Role for a Cardio-Oncologist. Journal of the American College of Cardiology 2013;61: 2363-2364. 


Okwuosa IS, Princewill O, Nwabueze C, et al.The ABCs of managing systolic heart failure: Past, present, and future. Cleve Clin J Med. 2016 Oct;83:753-765.

Link : The ABCs of managing systolic heart failure: Past, present, and future.

Reed BN, Sueta CA .A practical guide for the treatment of symptomatic heart failure with reduced ejection fraction (HFrEF). Curr Cardiol Rev. 2015;11:23-32.
Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. European Heart Journal (2011) 32, 670–679.

Sanderson J E. Heart failure with a normal ejection fraction.Heart 2007;93:155-158. doi:10.1136/hrt.2005.074187

Rose-Jones LJ, Rommel JJ, Chang PP. Heart failure with preserved ejection fraction: an ongoing enigma. Cardiol Clin. 2014; 32:151-61.

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Guidelines ESC Heart failure acute and chronic -2012


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


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


Coronary artery disease

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. 

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 useful to assess left ventricular ejection fraction (LVEF), which is an important prognostic factor that influences therapeutic decisions.

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. 

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.


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 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 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 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.


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:

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 ?


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).

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
 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.

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
Bleeding diathesis or INR

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).

Bibliography and links

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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.

Fathala A.  Myocardial Perfusion Scintigraphy: Techniques, Interpretation, Indications and Reporting Ann Saudi Med. 2011; 31: 625–634.

Noninvasive Testing for Coronary Artery Disease. 
Agency for Healthcare Research and Quality (AHRQ)Publication No. 16-EHC011-EF March 2016 .

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

Sianos G, Morel MA,, et al. The SYNTAX score: an angiographic tool grading the complexity of CAD. EuroInterv 2005; 1: 219-227

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.

2013 ESC guidelines on the management of stable coronary artery disease

ACC/AHA Guideline : Stable ischemic heart disease -2012

2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

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

ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation (2012)

2014 ESC/EACTS Guidelines on myocardial revascularization

Third universal definition of myocardial infarction

2016 ESC/EAS Guidelines for the Management of Dyslipidaemias

2016 European Guidelines on cardiovascular disease prevention in clinical practice

ESC Guidelines on the diagnosis and treatment of peripheral artery diseases

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