Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Huda A. Karman, M.D.

System leader: Sahar Memar Montazerin, M.D.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Listed in alphabetical order:

• Angiotensin
• Aortic body
• Autoregulation
• Baroreceptor
• Baroreflex
• Blood pressure
• Blood vessel
• Cardiac action potential
• Cardiac output
• Cardiac pacemaker
• Carotid body
• Central venous pressure
• Chronotropic
• Compliance
• Diastolic pressure
• Dromotropic
• Ejection fraction
• Electrical conduction system of the heart
• Electrocardiogram
• End-diastolic volume
• End-systolic volume
• Fick’s law of diffusion
• Frank-Starling law of the heart
• Heart
• Heart rate
• Inotropic
• Juxtaglomerular apparatus
• Mean arterial pressure
• Microcirculation
• Poiseuille’s law
• Pressure volume diagram
• Pulse pressure
• Renin
• Renin-angiotensin system
• Skeletal-muscle pump
• Starling equation
• Stroke volume
• Systolic pressure
• Total peripheral resistance
• Wiggers diagram

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The heart is the first functional organ in a vertebrate embryo. There are 5 stages to heart development.

The lateral plate mesoderm delaminates to form two layers: the dorsal somatic (parietal) mesoderm and the ventral splanchnic (visceral) mesoderm. The heart precursor cells come from the two regions of the splanchnic mesoderm called the cardiogenic mesoderm. These cells can differentiate into endocardium which lines the heart chamber and valves and the myocardium which forms the musculature of the ventricles and the atria.

The heart cells are specified in anterior mesoderm by proteins such as Dickkopf-1, Nodal, and Cerberus secreted by the anterior endoderm. Whether Dickkopf-1 and Nodal act directly on the cardiac mesoderm is the subject of research, but it seems that at least they act indirectly by stimulating the production of additional factors from the anterior endoderm. These early signals are essential for heart formation such that removal of the anterior endoderm blocks heart formation. Anterior endoderm is also sufficient to stimulate heart differientation since it can induce non-cardiogenic mesoderm from more posterior positions in the embryo to form heart.

The secretion of Wnt inhibitors (such as Cerberus, Dickkopf and Crescent) by the anterior endoderm also prevents Wnt3a and Wnt8 secreted by the neural tube from inhibiting heart formation. The notochord secretes BMP antagonists (Chordin and Noggin) to prevent formation of cardiac mesoderm in inappropriate places.

Other cardiogenic signals such as BMP and FGF activate the expression of cardiac specific transcription factors such as homeodomain protein Nkx2.5. Nkx2.5 activates a number of downstream transcription factors (such as MEF2 and GATA) which activate the expression of cardiac muscle specific proteins. Mutations in Nkx2.5 result in heart development defects and congenital heart malformations.

The cardiac precursor cells migrate anteriorly towards the midline and fuse into a single heart tube. Fibronectin in the extracellular matrix directs this migration. If this migration event is blocked, cardia bifida results where the two heart primordia remain separated. During fusion, the heart tube is patterned along the anterior/posterior axis for the various regions and chambers of the heart.

The heart tube undergoes right-ward looping to change from anterior/posterior polarity to left/right polarity. The detailed mechanism is unknown however the looping requires the asymmetrically localized transcription factor Pitx2. It is possible that the asymmetry is caused by the clockwise rotation of cilia in dispersing this transcription factor. Looping also depends on heart specific proteins activated by Nkx2.5 such as Hand1, Hand2, and Xin.

The cell fates of the heart chambers are characterized before heart looping but can not be distinguished until after looping. Hand1 is localized to the left ventricle while Hand2 is localized to the right ventricle.

Proper positioning and function of the valves is critical for chamber formation and proper blood flow. The endocardial cushion serves as a makeshift valve until then.

The human heart beats more than 3.5 billion times in an average lifetime.

The human embryonic heart begins beating approximately 21 days after conception, or five weeks after the last normal menstrual period (LMP), which is the date normally used to date pregnancy. The human heart begins beating at a rate near the mother’s, about 75-80 beats per minute (BPM). The embryonic heart rate (EHR) then accelerates linearly for the first month of beating, peaking at 165-185 BPM during the early 7th week, (early 9th week after the LMP). This acceleration is approximately 3.3 BPM per day, or about 10 BPM every three days, an increase of 100 BPM in the first month.^[1]

After peaking at about 9.2 weeks after the LMP, it decelerates to about 150 BPM (+/-25 BPM) during the 15th week after the LMP. After the 15th week the deceleration slows reaching an average rate of about 145 (+/-25 BPM) BPM at term. The regression formula which describes this acceleration before the embryo reaches 25 mm in crown-rump length or 9.2 LMP weeks is:

Age in days = EHR(0.3)+6

There is no difference in male and female heart rates before birth.^[2]

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Discomfort in the chest which can be squeezing, a heaviness, a tightness, a burning or an aching.

Recurring burning, aching, fatigue, or heaviness in the leg muscles with predictable level of walking, that resolves with a predictable duration of rest.

• Cough is defined as being a reflex explosive expiration that promotes the removal of secretions and foreign particles from the lungs, while preventing aspiration
• Coughing can take on two forms:

  • Nonproductive
  • Productive

• A cough can either be chronic or acute (coughing lasting less than three weeks)
• The production of sputum is important when assessing a cough
• The quality, quantity and circumstances of the sputum production surrounding the coughing episodes are also important

Dyspnea is an uncomfortable awareness of breathing, shortness of breath, or difficulty or distress in breathing. It is often associated with cardiac or pulmonary disease.

Orthopnea is dyspnea which occurs when lying flat, causing the person to have to sleep propped up in bed or sitting in a chair. Orthopnea is generally a symptom of heart failure. It can also occur in those with asthma and chronic bronchitis, as well as those with sleep apnea or panic disorder. The condition is often due to left ventricular failure and/or pulmonary edema. It is also associated with Polycystic Liver Disease. Patients with orthopnea often complain of waking up suddenly during the night ‘unable to breathe’ if they have slipped down from their pillows into the supine position. They may run to the window to ‘get some air’. It is commonly measured according to the number of pillows needed to prop the patient up to enable breathing (Example: “3 pillow orthopnea”). See also: Paroxysmal Nocturnal Dyspnea which means that a patient wakes up short of breath.

Paroxysmal nocturnal dyspnea (PND) is a medical symptom wherein people with congestive heart failure develop difficulties breathing after lying flat. PND commonly occurs several hours after a person with heart failure has fallen asleep. PND resolves quickly once a person awakens and sits upright.

PND is caused by increasing amounts of fluid entering the lung during sleep and filling the small, air-filled sacs (alveoli) in the lung responsible for absorbing oxygen from the atmosphere. This fluid typically rests in the legs during the day when the individual is walking around and redistributes throughout the body (including the lungs) when recumbent. PND is a sign of severe heart failure

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• Introduction to EKG
• How to read an EKG
• Normal sinus rhythm
• QRS axis and voltage
• Overall overview on electrocardiography

• P wave
• QRS complex
• ST segment
• T wave

• PR interval
• QRS interval
• QT interval
• ST interval

• Delta wave
• H wave
• K wave
• Low QRS voltage
• Nonspecific ST-segment and T-wave changes
• NSSTW changes
• Osborn wave
• P wave alternans
• Poor R wave progression
• PR interval alternans
• QRS complex alternans
• QT prolongation
• Retrograde P wave
• Sine wave pattern
• T wave alternans
• T wave inversion
• Tombstone ST elevation
• U wave

• Cardiac pacemaker
• SA node
• AV node
• Bundle of His
• Purkinje fibers

• Atrial fibrillation
• Atrial flutter
• Ectopic atrial rhythm
• Multifocal atrial tachycardia (MAT)
• Paroxysmal atrial tachycardia (PAT) with block
• Premature atrial contractions (PAC)
• Sinus tachycardia
• Supraventricular tachycardia
• Wandering atrial pacemaker

• Accelerated idioventricular rhythm
• Ventricular fibrillation
• Ventricular parasystole
• Ventricular tachycardia
• Wide complex tachycardias

• Sinus bradycardia
• First degree AV block
• Second degree AV block
• Complete or third-degree AV block
• Concealed conduction
• AV junctional rhythms
• Wolff-Parkinson-White syndrome
• Left bundle branch block
  • Left anterior hemi-block
  • Lefo posterior hemi-block
• Right bundle branch block
• Trifascicular block

• Left ventricular hypertrophy (LVH)
• Right ventricular hypertrophy (RVH)
• Biventricular hypertrophy
• Left atrial enlargement
• Right atrial enlargement
• Biatrial enlargement

• NSTEMI
• STEMI
• Tombstone ST elevation
• Right ventricular myocardial infarction
• Atrial infarction

• Wolff-Parkinson-White syndrome
• Lown-Ganong-Levine syndrome
• Mahaim type preexcitation

• Arrhythmogenic right ventricular dysplasia
• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy

• Dextrocardia
• Atrial septal defect
• Ventricular septal defect
• Tetralogy of Fallot
• The heart in conjoined twins
• Congenital heart block

• Brugada syndrome

• Pericarditis
• Myocarditis
• Cardiac tamponade
• Sick sinus syndrome
• Long QT syndrome

• CNS disease
• Cardiac transplantation
• Trauma
• Hypothermia
• Insect bites

• Hyperkalemia
• Hypokalemia
• Hypercalcemia
• Hypocalcemia

• Left axis deviation
• Right axis deviation
• Q wave in lead III
• T wave inversion
• Increased R/S ratio in V1 and V2
• ST-segment depression (usually after anesthesia for C-section)

• Adenosine
• Amiodarone
• β-blockers
• Bretylium
• Calcium channel blockers
• Digitalis
• Disopyramide
• Encainide
• Flecainide
• Lidocaine
• Lithium
• Phenothiazines
• Phenytoin
• Procainamide
• Propafenone
• Quinidine
• Tocainide
• Tricyclic antidepressants

• EKG Artifacts
• EKG lead placement errors
• EKG in a patient with a pacemaker
• EKG in athletes
• Persistent juvenile T-wave pattern
• Postprandial EKG changes

• History of the EKG
• SCP-ECG
• 80 lead ECG

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Editor(s)-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Ernest Gervino, Ph.D.; Brenna Southern, M.D.; Kapil Kumar, M.D.; Bruce D. Nearing, Ph.D.; Richard L. Verrier, Ph.D.

To read more about Exercise Tolerance Test Time as an Endpoint for Clinical Trials Evaluating Therapies for Refractory Angina, click here.

An exercise stress test (EST) is an evaluation modality used in cardiology in which the ability of the heart to respond to stress, either actually induced by exercise or stimulated by pharmacologic maneuvers, is measured in a controlled clinical setting. The image created by its recording is known as an electrocardiogram or ECG.

The test is typically included in the initial evaluation of suspected ischemic heart disease, and as a prognostic indicator after myocardial infarction.^[1]

• Low cost
• Short duration
• Functional status evaluation
• High sensitivity in 3 VD or left main disease
• Useful prognostic information

• Sub-optimal sensitivity in the detection of single vessel disease (50%), 85% in the presence of three vessel disease
• In all patients, overall sensitivity 68%, specificity 77%
• Beta blocker use is associated with a higher rate of false negatives (fail to achieve rate pressure product)
• Non diagnostic in patients with abnormal baseline EKG (dig, LVH, WPW)
• Poor specificity in certain patient populations: premenopausal women, LVH, dig, IVCD, hypokalemia, hyperventilation, severe hypertension, resting ST abnormalities
• The negative predictive value in women of low to intermediate risk is high, the positive predictive value in men is high
• Need to achieve > 85% of maximum heart rate for maximizing accuracy
• Its main values lies in excluding CAD in patients with a low pre-test probability of CAD based on gender and age.

• Simultaneous evaluation of perfusion and function with gated SPECT

• Higher sensitivity and specificity than exercise EKG: For exercise or pharmacologic SPECT imaging with Tl or Tc, in patients with chest pain the sensitivity for the detection of CAD is 85% to 90%. Specificity for excluding CAD is in the 90% range. Good in patients with LVH, dig, IVCD etc. ST segment depression response higher rate pressure product than does a perfusion abnormality with tracers. Therefore they are more sensitive. Adding stress perfusion imaging to the exercise ECG stress test greatly assists in differentiating true positive from false positive ETT ST segment depression. For single vessel disease, the sensitivity is 25% higher with SPECT imaging compared with exercise testing. The sensitivity for detecting 3VD with exercise SPECT is 95% to 100%.

• High specificity with Tc labeled agents: Half life is shorter than Tl, therefore dose is higher, therefore image is brighter and better. Also allows gated assessment of LV thickening.

• Studies can be performed in almost all patients
• Significant additional prognostic information, can quantitate LV function
• Comparable accuracy with pharmacologic stress testing
• Viability and ischemia when assessed simultaneously
• Quantitative image analysis

• Suboptimal specificity with thallium imaging, with a high false positive rate in many labs, particularly among women and obese patients.

• Long procedure time with Tc agents, higher costs than ETT
• Radiation exposure
• Poor images in obese patients

• Pharmacologic stress testing: sensitivity and specificity are similar for persantine and adenosine. Dobutamine is used in those patients with a history of bronchospasm, or for those patients who have consumed coffee before the procedure. Pharmacologic testing is the preferred method in patients with LBBB.

• Women with chest pain who are referred for exercise or pharmacologic stress testing benefit the most from the enhanced accuracy of Tc imaging. Both Tl and Tc had a sensitivity of about 70%, but the specificity rose to 92% with Tc. Most labs now use Tc because of its improved specificity, the ability to gait the images and assess regional wall thickening. Mild non reversible defects that show preserved systolic thickening usually represent attenuation artifacts, however, if there is abnormal wall thickening, then this is most likely scar.

• Higher sensitivity and specificity than exercise EKG: Metanalysis showed sensitivity of 84%, specificity 86%. Marked variation across trials though, highly operator dependent. If the max heart rate is < 85% of age predicted, then sensitivity drops to 42%. Sensitivity is 10% lower in women than in men, specificity is the same across genders. In women with single vessel disease the sensitivity was only 40%, if there was 2 or 3 vessel disease, this number increased to 60%.

• Additional prognostic value over exercise EKG
• Dobutamine stress has higher sensitivity than does pharmacologic stress
• Time to complete examination is short
• Identification of co-existent structural cardiac abnormalities (valvular disease)
• Simultaneous evaluation of perfusion with contrast agents
• Relatively lower costs than with other techniques
• No radiation

• Decreased sensitivity for the detection of single vessel disease or mild stenosis with post exercise imaging
• Inability to image the entire ventricle in some patients
• Highly operator dependent in the analysis of images
• No quantitative image analysis
• Poor windows in patients with COPD
• Infarct zone ischemia less well detected

• Both have a higher sensitivity and specificity than regular exercise EKG testing
• Both provide functional information that EKG testing does not
• Both provide information about myocardial viability, which the angiogram does not

Noninvasive, safe and repeatable, no radiation exposure, quick, little sophisticated equipment and portable, low costs, can identify co-existing valvular heart disease

Images are difficult to obtain at peak exercise, an ischemic response is required to observe wall motion abnormalities, wall motion can recover quickly in the presence of mild ischemia, detection of residual ischemia is difficult in an akinetic wall zone, the technique is highly operator dependent, good quality images were only acquired in 70% of cases.

Does not require an ischemic response to be abnormal, just requires an abnormality in flow reserve, sensitivity is slightly higher by about 8-10 percentage points (mostly because the ability to detect single vessel disease or mild stenoses of 50-70% is not as good with stress Echo), can see defects in areas that contain scar and viable myocardium, acquisition of images is not operator dependent, in virtually 100% of patients diagnostic images are obtained, with Tc simultaneous assessment of perfusion and function is obtained, resting LV ejection fraction can be obtained, vasodilator SPECT has significantly higher sensitivity than vasodilator stress ECHO, dobutamine ECHO is associated with higher sensitivity and specificity than vasodilator ECHO.

Longer imaging protocols, greater expense of equipment, must inject and store radiopharmaceuticals, inability to visualize the heart in real time, lower spatial resolution than ECHO, higher costs to patients.

In general, the sensitivity is lower for stress ECHO while the specificity is higher.

• 1 mm or more of horizontal or downsloping ST depression is associated with a poor prognosis
• Failure to achieve 6 METS is associated with an elevated mortality rate over the next 2.5 years.
• Failure of heart rate to rise is associated with higher mortality, even after adjusting for perfusion defects.
• Failure to reach 85% of age adjusted max HR is associated with a RR of 1.85 in mortality.
• Limitation of ETT is the fact that the magnitude of ST depression is not strongly associated with the extent of CAD
• Exercise testing alone has excellent prognostic ability among patients with atypical chest pain or non anginal pain who have a normal EKG at baseline. If these patients have a normal ETT, the prognosis is excellent.

• The following are associated with a poor prognosis:

  • 20% of the LV is a perfusion defect
  • Defects in more than one distribution suggestive of multivessel CAD
  • A large number of non reversible defects
  • Transient LV cavitary dilation
  • Increased lung uptake
  • Resting LVEF of < 40%

• Normal thallium: Mortality 1% per year
• Normal Tc: annual mortality 0.6%, 12 fold higher if there is a Tc defect
• The positive predictive value of stress myocardial perfusion imaging and stress ECHO is low: That is the percentage of people who die or sustain an MI is low among patients with abnormal findings. On the other hand the negative predictive value is high and exceeds 95%.

^[2]

Rest and delayed redistribution is the most common radionuclide method used to assess viability. Uptake of Tl is related not only to blood flow, but also to membrane integrity. Myocardial stunning or hibernation does not result in a reduction in Tl extraction as long as the sarcolemmal membrane does not sustain irreversible ischemic damage. 60 to 70% of asynergistic segments will show > a 50% improvement after revascularization.

Same as above, as usual a better signal with Tc, can also assess regional wall thickening. If thickening is present, then viability is likely.

• Considered by many to be the gold standard. Can be used to assess perfusion and metabolism simultaneously. If there is mismatch in perfusion and metabolism, then the tissue is viable. If there is a match, then there is scar.

• Dobutamine: Enhanced systolic contractility with low dose dobutamine is associated with recovery.

Stress testing has frequently been used to assess adult patients with suspected or known coronary artery disease (CAD) based on pre-test probability. Pre-test probability is the assessment of a patient and their likelihood of CAD based on clinical history and symptoms. Stress testing to diagnose myocardial ischemic syndrome is usually indicated only in patients with an intermediate pre-test probability.^[3]

The average age of a patient who undergoes a stress test is typically between 45-60 years. Increasing age is one of many positive risk factors for CAD. However, there have been several cases in which young adults and adolescents have presented with chest pain and were found to have had a myocardial infarction (MI). ^[4] Since chest pain can be a complaint among children, the question becomes whether or not an emergent stress test is needed.

The most common reason for stress testing is chest pain. All patients who present with acute or chronic chest pain need to be evaluated to determine the course or urgency of further non-invasive vs. invasive testing. Inpatient stress testing can be done if a recent MI or an acute unstable coronary syndrome has been excluded.

Among children presenting with chest pain, the symptoms often tend to be benign. ^[5] Given the fact that the majority of children have no probable cardiac risk factors, their pre-test probability is already very low. Yet there are several conditions that can cause ischemic chest pain and other cardiac abnormalities so a thorough careful history and physical examination should always be performed. The presenting symptom can be secondary to congenital defects as well as acquired diseases. Kawasaki disease has a common manifestation of coronary artery aneurysms which can progress to coronary stenosis. ^[6] Acute MI is one of the main causes of death in children with Kawasaki disease. Another acquired condition is sickle cell disease in which children can frequently present with chest pain, have an MI and have normal coronary arteries. ^[7] Other issues that could cause ischemic chest pain are coronary vasospasm, pericarditis or myocarditis, cocaine use, or other conditions causing anatomic congenital cardiovascular abnormalities.

Acute symptoms in children should be dealt with accordingly to rule out an MI, congenital defects or diseases. Based on above indications, an emergent stress test may not be warranted. To help determine the etiology of the symptom, ECG, echocardiogram, MRI, cardiac enzymes, drug screening, blood testing for hypercoagulability and coronary angiograms may be more useful. Or for chronic chest pain associated with exertion, an outpatient stress test could also be helpful.

Whether or not stress testing is emergent in children should again be considered similarly to adult emergent stress testing. Comprehensive assessment of acute or chronic problems and the consideration of the child’s pre-test probability being significantly low are compelling points that an emergent stress test may not be necessary.

Across the past decade, a sizeable body of evidence has been amassed indicating that measurement of T wave alternans (TWA), a beat-to-beat fluctuation in the morphology of the T wave, during exercise is useful in assessing risk for life-threatening arrhythmias.

TWA is a marker of repolarization instability and an indicator of a vulnerable myocardial substrate. This electrocardiographic phenomenon parallels the beat-to-beat oscillation of action potential duration (APD) at the level of cardiac myocytes. The cellular mechanism has been linked primarily to an aberration in intracellular calcium, which results in fluctuation of calcium transients from one beat to the next. This oscillation in APD can be solely a temporal event (concordant alternans) or both a temporal and spatial occurrence (discordant alternans). Discordant alternans has the potential to create steep repolarization gradients leading to transient unidirectional block, a pre-requisite for reentrant arrhythmias ^{[8] [9]}

Until recently, TWA analysis has largely involved frequency-domain based spectral analysis. The spectral method (SM) requires provocative testing to raise and plateau the heart rate. The level of TWA detected is in the range of a few microvolts and thus cannot be observed by visual inspection. SM is the first and most widely studied commercially available algorithm (Cambridge Heart, Inc.). It employs a fast Fourier transformation of the electrocardiogram (ECG) across 128 consecutive beats into the frequency domain and employs specialized electrodes to minimize noise. The power of the spectrum at 0.5 cycle per beat (occurring on every other beat) between the JT segment is defined as the alternans power. An alternans level (Valt) >1.9 μV, greater than 3 times the standard deviation of noise (k score), and sustained for at least one minute at stable heart rates <110 beats per minute is considered a positive test, indicating that TWA is present. A negative test is defined as one that has a Valt of <1.9 μV at a heart rate >105 bpm without significant noise or premature beats. Tests that do not strictly meet the positive or negative test definitions are referred to as indeterminate ^[10] and occur in 20 to 40% of all cases. Most recent studies using SM have grouped positive and indeterminate tests together as “abnormal” or “non-negative,” since the risk of death or sustained ventricular arrhythmias in patients with indeterminate tests due to patient factors is as high as that of patients with positive tests. ^[11]

A recently developed, FDA cleared commercial method (GE Healthcare, Inc.) is time domain modified moving average (MMA) developed at Beth Israel Deaconess Medical Center (Nearing and Verrier 2002). This technique was developed to circumvent the stationarity requirements of SM, which mandates stabilization of heart rate for several minutes given the fast Fourier transform. The requirement for specialized electrodes is also eliminated through the use of advanced noise reduction algorithms. The MMA method separates odd and even beats into separate bins and creates median templates for both the odd and even complexes every 15 seconds. ^[12] These templates are then superimposed and the entire JT segment is analyzed for alternation. The peak difference between the odd and even median complexes at any point within the JT segment is defined as the TWA value. These templates of superimposed complexes may be examined visually to verify TWA presence and magnitude. Noise measurements are in part derived from mismatch of the median templates outside of the JT segment. The moving average allows control of the influence of new incoming complexes on the median templates with an adjustable update factor. A lower update factor provides greater sensitivity in detecting transient surges in TWA.

Results from SM and MMA are highly comparable, although the TWA values reported with the MMA algorithm are consistently larger by a factor of 4 to 10. This difference is mainly attributable to the fact that SM reports the average TWA level across the entire JT segment for 128 beats that is above the noise level, while MMA method reports the peak TWA level at any point within the JT segment for each 15-second beat stream, with the noise level reported separately.

The majority of clinical studies focusing on TWA as a risk stratification tool have enrolled CAD patients with EF 40% and employed the SM. In 2005, Gehi and colleagues ^[13] conducted a meta-analysis of 19 prospective studies of exercise-based TWA testing with SM that enrolled a total of 2608 patients. The majority of these patients had CAD, and half had depressed EF, but only a small percentage had a history of ventricular arrhythmias. Positive TWA test results conveyed an average 3.77-fold risk of future ventricular tachyarrhythmic events when compared to patients with negative TWA test results. The negative predictive value (NPV) of TWA was 97.2%. However, its positive predictive value (PPV) was quite poor, generally <30% for all subgroups.

By virtue of its excellent NPV, TWA testing has been presented as a means of identifying those patients who are least likely to experience a future ventricular tachyarrhythmic event and thus least likely to benefit from ICD implantation.

Only one large prospective observational trial has investigated TWA in a broader population. The incidence of SCD in this subgroup of patients, however, is relatively low; rendering it even more difficult to identify those most likely to benefit from ICD implantation even though the absolute number of SCD events is higher in this population than in those with depressed EF. ^[14] Nieminen and coworkers (2007) provided evidence that TWA is also suitable as a screening tool in the general population of patients with preserved ejection fraction and can be performed during routine exercise stress testing. They applied the MMA method in 1037 consecutive patients referred for exercise testing and reported that TWA 65μV recorded in the precordial leads predicted all-cause death (RR= 3.3), cardiovascular mortality (RR=6.0), and sudden cardiac death (RR=7.4) across the 44 ±7 month follow-up. The analysis window was restricted to heart rates 125 beats/min in order to minimize the effects of noise.

Most recently, the REFINE study ^[15] enrolled 322 post-MI patients with ejection fraction 50% and measured TWA at 10 to 14 weeks. Spectral analysis was performed during the specialized exercise protocol, and MMA was employed during post-exercise recovery. Exner and colleagues (2007) determined that the predictivity of the spectral and MMA methods for TWA analysis is similar, with hazard ratios in the range of 2.75-2.94 for cardiac death or arrest during 47 months following the index event. Combining the TWA test results with heart rate turbulence, a noninvasive marker of autonomic tone, accurately predicted risk of cardiac death or arrest with a hazard ratio of 5.2 and identified the majority of patients destined to suffer serious events.

Collectively, sound scientific and clinical evidence support the utility of TWA testing for sudden death risk stratification during exercise. With the advent of time-domain based TWA analysis, this measurement can be performed seamlessly during the course of routine clinical exercise stress testing as well as ambulatory ECG monitoring. While TWA testing has been focused largely on guiding ICD implantation for primary prevention, there may be a greater role for TWA analysis in screening the broader, low-risk population and for evaluating the effectiveness of medical therapy.

Since sudden cardiac death results from diverse pathologic mechanisms, involving derangements in myocardial substrate and altered autonomic function, it is unlikely that any single parameter will adequately represent the complex factors that lead to lethal ventricular arrhythmias. Therefore, it will be valuable to examine whether combinations of several risk stratification parameters may be more effective than any individual parameter as observed in the REFINE study.^[16]

• Electrocardiogram
• Cardiology
• Myocardial infarction
• Emergent Stress Testing in Young People [2]
• T Wave Alternans for Risk Stratification during Exercise Stress Testing [3]

• Modified Gervino Protocol
• Emergent Stress Testing in Young People [4]
• T Wave Alternans for Risk Stratification during Exercise Stress Testing [5]

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• Cardiac electrophysiology (also referred to as clinical cardiac electrophysiology , or electrophysiology) is the science of the mechanisms, functions, and performance of the electrical activities of specific regions of the heart.
• The normal electrical conduction in the heart allows the impulse that is generated by the sinoatrial node (SA node) of the heart to be propagated to (and stimulate) the myocardium (Cardiac muscle). The myocardium contracts after stimulation. It is the ordered stimulation of the myocardium that allows efficient contraction of the heart, thereby allowing blood to be pumped throughout the body.

• Proper cardiac function heavily depends on the ability of the cardiomyocytes to receive and propagate an electrical impulse allowing the heart to contract.
• These impulses, known as action potentials, originate and travel through the cardiac conduction system.
• A time-ordered propagation of the electrical impulse through the myocardium allows efficient contraction of all four chambers of the heart, starting with the atria pumping the blood toward the ventricles, followed by the ventricles which contribute to the pulmonary and systemic circulation.

• The sinus (sinoatrial) node
• The internodal tracts
• The atrioventricular (AV) node
• The His/AV bundle
• The right and left bundle branches,
• The Purkinje fibers.

• The initial cardiac impulse, produced by pacemaker cells, originates in the sinoatrial (SA) node at the intersection of the right atrium and the superior vena cava.
• This action potential is the trigger of every cardiac cycle, initiating the atrial then ventricular contractions; it is henceforth responsible for the rhythmic beating of the heart.
• This action potential then propagates as a wave of depolarization through the internodal tracts initiating atrial contraction and then converging at the AV node.
  • The convergence occurs because, in a normal heart, the AV node is the only electrical connection between the atria and the ventricles.
  • The conduction of this potential is delayed at the AV node mainly due to the slower depolarization in these cells.
  • This delay is represented as the PR interval of the ECG.
• The electrical impulse then moves to the ventricles by means of the AV or His bundle located in the superior portion of the interventricular septum.
• It then continues moving apically and propagating through both [[]]ventricles via the right and left bundle branches, and the Purkinje fibers.^[1][2][3][4]

• 
  Section of the heart showing the ventricular septum.
• 
  Schematic representation of the atrioventricular bundle of His.

• Similarly to skeletal muscle cells which are also striated muscles, the cardiomyocytes contract in response to a rapid alteration in the cell membrane’s potential.
• However, the cardiomyocytes differ from skeletal muscle cells by three important variations that are essential for cardiac function:
  • 1) They can self-generate a change in cell membrane potential.
  • 2) The action potential can be transmitted directly from cell to cell.
  • 3) The action potentials have a significantly longer duration.

• All cells including cardiomyocytes have a resting membrane potential that is maintained assuming there is no electrical charge crossing the membrane from the intracellular towards the extracellular milieu or vice versa.
• This potential is estimated to be –80 to –90 mV.

• The most crucial ions that determine this resting potential are:
  • Sodium (Na+)
  • Calcium (Ca2+)
  • Potassium (K+)
• Sodium (Na+) and calcium (Ca2+) are most present in the interstitial fluid, while potassium (K+) is more present in intracellularly.

• These ions are lipid insoluble which prevents them from crossing the lipid bilayer or the cell membrane.
• Alternatively, ions cross via specific protein structures in the cell membrane that may be either: ion channels, ion pumps, or ion exchangers.
• These transmembrane proteins are highly specific and allow only one type of ion to pass through which allows good maintenance of the membrane potential.
• Ion channels can be opened, inactivated or closed depending on complex factors that modulate their activity.

• The cardiac contraction action potential is divided into 5 phases.

• The initial rapid increase in the transmembrane potential from -80mV to approximately +30mV constitutes the Phase 0 or the depolarization phase.
• This depolarization results from a rapid increase in the membrane permeability to Na+ ions via opening of voltage-dependent fast Na+ channels allowing Na+ ions to move intracellularly according to their electrochemical gradient.
• Following the conduction of an action potential, a recovery phase is attained where a large number of Na+ channels are inactivated, preventing the conduction of a second action potential.
• When the membrane is fully repolarized, these channels are reactivated and allow the conduction of the following action potential.

• The phase I of the action potential, known as the initial rapid repolarization ensues, resulting from K+ and Cl- ion flux across the membrane.
• This forms the notch seen in the action potential following the depolarization.

• Phase II, almost exclusive to cardiomyocytes, represents a plateau in the membrane potential as an outcome of the equilibrium between Ca2+ influx and K+ outflow.
• The channels responsible for this Ca2+ influx are known as the L-type calcium channels, which are activated rapidly when the membrane potential reaches -50mV, but are slowly inactivated thereafter.
• Throughout this plateau phase, few Na+ channels also remain active.
• These are Na+/Ca2+ exchangers that allow 1 ion of calcium to move outside the cell for every 3 molecules of sodium moving inside the cell.

• The third phase, also known as rapid repolarization, depicts the restoration of a resting membrane potential.
• It is initiated by inactivation of the L-type calcium channels and an increase in K+ outflow.
• This change in potassium across the membrane is related to 3 K+ currents:
  • 1) Inwardly rectifying K+ current (IK1) à Produces the resting membrane potential
  • 2) Transient outward K+ current (ITO) à Accounts for initial part of repolarization
  • 3) Delayed outward K+ current (IK) à Responsible for final part of repolarization

• After repolarization has occurred, intracellular Na+ and extracellular K+ are rearranged via the Na+/K+ ATPase pump.
  • The ATPase moves 3 sodium ions out for every 2 potassium ions moved intracellularly.
• Equilibrium of ions across the membrane is also achieved via the Na+/Ca2+ exchangers.

• The phase IV of the action potential is characterized by a diastolic depolarization that is both spontaneous and slow.
• This phase provides cardiac cells with features of automaticity.
• In a normal functioning heart, only the sinoatrial node is able to reach a threshold potential during phase IV making it the pacemaker of the heart.
• Nevertheless other cells including those in the AV node, the His bundle, and the Purkinje fibers are able to reach a threshold and fire automatically if they are not suppressed by the SA node, which is true in some disease entities.

• Inward Ca2+ current
• Delayed outward K+ current
• IF Currents – Inward sodium-potassium currents activated if membrane repolarizes below the If threshold
• T-type Ca2+ channel – Releases calcium from internal stores

• 1) The slope of diastolic depolarization
• 2) The maximal diastolic potential
• 3) The threshold potential

• All these factors are controlled by the autonomic nervous system allowing for the modulation of the rate of SA node firing and subsequently the heart rate.^[1][5][3][4]

• An electrophysiologic study is a term used to describe a number of invasive (intracardiac) and non-invasive recording of spontaneous electrical activity as well as of cardiac responses to programmed electrical stimulation.
• These studies are performed to assess arrhythmias, elucidate symptoms, evaluate abnormal electrocardiograms, assess risk of developing arrhythmias in the future, and design treatment.
• These procedures increasingly include therapeutic methods (typically radiofrequency ablation) in addition to diagnostic and prognostic procedures.
• Other therapeutic modalities employed in this field include antiarrhythmic drug therapy and implantation of pacemakers and implantable cardioverter-defibrillators.

• A specialist in cardiac electrophysiology is known as a cardiac electrophysiologist, or (more commonly) simply an electrophysiologist. Cardiac electrophysiology is considered a subspecialty of cardiology, and in most countries requires two or more years of fellowship training beyond a general cardiology fellowship. They are trained to perform interventional cardiac EP procedures as well as surgical device implantations.

• Ambulatory electrocardiographic monitoring (Holter recording and interpretation; loop recording and interpretation)
• Tilt table testing
• Signal-averaged electrocardiogram (SAECG) interpretation, also referred to as “late potentials” reading
• Electrophysiologic study (EPS)
  • Pacing and recording electrodes are inserted either in the esophagus (intra-esophageal EPS) or, through blood vessels, directly into the heart chambers (intra-cardiac EPS) in order to measure electrical properties of the heart. In addition, intra-cardiac EPS electrically stimulates the heart and induces arrhythmias for diagnostic purposes (“programmed electrical stimulation”).

Electrophysiologists play a role in:

• The initial administration and monitoring of the effect of drugs for treatment of heart rhythm disorders
• The management of severe or life threatening arrhythmias
• The management of arrythmias requiring multiple drugs use

• Ablation therapy is the catheter based creation of lesions in the heart with radiofrequency energy, cryotherapy (destructive freezing), or ultrasound energy in order to cure or control arrhythmias (see radiofrequency ablation). Ablation is usually performed during the same procedure as the electrophysiology study which induces and confirms the diagnosis of the arrhythmia for which ablation therapy is sought.

• It includes ablation for arrhythmias such as: AV nodal reentrant tachycardia, accessory pathway mediated tachycardia and atrial flutter.
• This procedure is usually performed using intracardiac catheters , fluoroscopy (a real-time X-ray camera), and electrical recordings from the inside of the heart.

• It includes ablation for arrhythmias such as: multifocal atrial tachycardia, atrial fibrillation, and ventricular tachycardia.
• In addition to the apparatus used for a “non-complex” ablation, these procedures often make use of sophisticated computer mapping systems to localize the source of the abnormal rhythm and to direct delivery of ablation lesions.

• Implantation of single and dual chamber pacemakers and defibrillators
• Implantation of “biventricular” pacemakers and defibrillators for patients with congestive heart failure
• Implantation of loop recorders (implanted ECG recorders for long term monitoring of ECG to allow for diagnosis of an arrhythmia)
• Clinical follow up and reprogramming of implanted devices

• Mechanism of Arrhythmias
• Diseases of the Conduction System and Bradyarrhythmias
• Narrow Complex Tachycardias
  • Atrial Flutter
  • Atrial Fibrillation
  • Atrial Tachycardia
  • AV Nodal Reentrant Tachycardia
  • Circus Movement Tachycardia
• Wide Complex Tachycardias
  • WPW Syndrome
  • Ventricular Tachycardia
    • Ventricular Tachyarrhythmias in Structurally Normal Hearts
  • Brugada Syndrome
  • Long QT Syndrome
• Ventricular Tachyarrhythmias, Cardiac Arrest and Sudden Cardiac Death
• Arrhythmias in Pregnancy

• Antiarrhythmic Medications
• Indications for Pacemakers
• Indications for an ICD
• Cardiac Resynchronization Therapy
• Catheter ablation

• Clinical cardiac electrophysiology
• Electrical conduction system of the heart
• Electrocardiogram (EKG)
• Basic Principles of ECG Interpretation
• Electrophysiologic study
• Cardiology
• Cardiac arrhythmia

• Cardiac Electrophysiology Society
• Heart Rhythm Society
• International Winter Arrhythmia School

Template:WikiDoc Sources CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; David E. Winchester M.D. M.S.

This chapter presents a brief overview of cardiac imaging techniques. For a detailed discussion of each of the imaging technoloies, please view the chapter on that imaging technology.

• Least expensive, most versatile.
• Portable, immediately available
• Preferred initial technique to diagnose heart muscle disease of unknown etiology.
• Regional thickening can be assessed on ECHO and not other techniques and this is a better marker of regional function than is regional wall motion (cant be seen on nuclear or angio studies, MRI can assess though)
• ECHO is not as good at assessing quantitative ejection fraction (SPECT, angio, RVG are better at this).
• More sensitive than EKG in diagnosis of LVH.
• Excellent in estimating LV mass

• Good for quantitating LV and RV EFs. Excellent for following the wall motion in patients treated with chemotherapeutic agents.
• Good for wall motion.
• In MI does not tell you about infarct expansion, MR, LV thrombus, regional thickening abnormalities.

• Permits evaluation of regional thickening, global LV function and myocardial perfusion.

• Good regional and global cardiac function.
• With contrast agents, good perfusion data
• Superior for congenital, aortic disease, anomalous coronary arteries, and RV dysplasia
• Cost benefit ratios of echo and nuclear make them superior for LV function assessment
• May be best technique for quantitating LV mass
• As a research tool may be useful in the assessment of LV remodeling

• Gold standard in the assessment of wall motion but not in the assessment of wall thickening.
• LVEF and absolute volumes are highly reproducible
• LVH and LV mass are better quantitated with echo and MRI
• Left to right shunts are most accurately quantitated with cardiac cath over echo and MRI

• Strengths

  • Low cost
  • Short duration
  • Functional status evaluation
  • High sensitivity in 3 VD or left main disease
  • Useful prognostic information

• Limitations
• Suboptimal sensitivity in the detection of single vessel disease (50%), 85% in the presence of three vessel disease
• In all patients, overall sensitivity 68%, specificity 77%
• Beta blocker use is associated with a higher rate of false negatives (fail to achieve rate pressure product)
• Non diagnostic in patients with abnormal baseline EKG (dig, LVH, WPW)
• Poor specificity in certain patient populations: premenopausal women, LVH, dig, IVCD, hypokalemia, hyperventilation, severe hypertension, resting ST abnormalities
• The negative predictive value in women of low to intermediate risk is high, the positive predictive value in men is high
• Need to achieve > 85% of maximum heart rate for maximizing accuracy
• Its main values lies in excluding CAD in patients with a low pre test probability of CAD based on gender and age.

• Strengths

  • Simultaneous evaluation of perfusion and function with gated SPECT
  • Higher sensitivity and specificity than exercise EKG: For exercise or pharmacologic SPECT imaging with Tl or Tc, in patients with chest pain the sensitivity for the detection of CAD is 85% to 90%. Specificity for excluding CAD is in the 90% range. Good in patients with LVH, dig, IVCD etc. ST depression response higher rate pressure product than does a perfusion abnormality with tracers. Therefore they are more sensitive. Adding stress perfusion imaging to the exercise ECG stress test greatly assists in differentiating true positive from false positive ETT ST segment depression. For single vessel disease, the sensitivity is 25% higher with SPECT imaging compared with exercise testing. The sensitivity for detecting 3VD with exercise SPECT is 95% to 100%.
  • High specificity with Tc labeled agents: Half life is shorter than Tl, therefore dose is higher, therefore image is brighter and better. Also allows gated assessment of LV thickening.
  • Studies can be performed in almost all patients
  • Significant additional prognostic information, can quantitate LV function
  • Comparable accuracy with pharmacologic stress testing
  • Viability and ischemia when assessed simultaneously
  • Quantitative image analysis

• Limitations

  • Suboptimal specificity with thallium imaging, with a high false positive rate in many labs, particularly among women and obese patients.
  • Long procedure time with Tc agents, higher costs than ETT
  • Radiation exposure
  • Poor images in obese patients
  • Pharmacologic stress testing: sensitivity and specificity are similar for persantine and adenosine. Dobutamine is used in those patients with a history of bronchospasm, or for those patients who have consumed coffee before the procedure. Pharmacologic testing is the preferred method in patients with LBBB.
  • Women with chest pain who are referred for exercise or pharmacologic stress testing benefit the most from the enhanced accuracy of Tc imaging. Both Tl and Tc had a sensitivity of about 70%, but the specificity rose to 92% with Tc. Most labs now use Tc because of its improved specificity, the ability to gait the images and assess regional wall thickening. Mild non reversible defects that show preserved systolic thickening usually represent attenuation artifacts, however, if there is abnormal wall thickening, then this is most likely scar.

• Strengths

  • Higher sensitivity and specificity than exercise EKG: Metanalysis showed sensitivity of 84%, specificity 86%. Marked variation across trials though, highly operator dependent. If the max heart rate is < 85% of age predicted, then sensitivity drops to 42%. Sensitivity is 10% lower in women than in men, specificity is the same across genders. In women with single vessel disease the sensitivity was only 40%, if there was 2 or 3 vessel disease, this number increased to 60%.
  • Additional prognostic value over exercise EKG
  • Dobutamine stress has higher sensitivity than does pharmacologic stress
  • Time to complete examination is short
  • Identification of co-existent structural cardiac abnormalities (valvular disease)
  • Simultaneous evaluation of perfusion with contrast agents
  • Relatively lower costs than with other techniques
  • No radiation

• Limitations

  • Decreased sensitivity for the detection of single vessel disease or mild stenosis with post exercise imaging
  • Inability to image the entire ventricle in some patients
  • Highly operator dependent in the analysis of images
  • No quantitative image analysis
  • Poor windows in patients with COPD
  • Infarct zone ischemia less well detected

• Both have a higher sensitivity and specificity than regular exercise EKG testing
• Both provide functional information that EKG testing does not
• Both provide information about myocardial viability, which the angiogram does not

• Noninvasive, safe and repeatable, no radiation exposure, quick, little sophisticated equipment and portable, low costs, can identify co-existing valvular heart disease

• Images are difficult to obtain at peak exercise, an ischemic response is required to observe wall motion abnormalities, wall motion can recover quickly in the presence of mild ischemia, detection of residual ischemia is difficult in an akinetic wall zone, the technique is highly operator dependent, good quality images were only acquired in 70% of cases.

• Does not require an ischemic response to be abnormal, just requires an abnormality in flow reserve, sensitivity is slightly higher by about 8-10 percentage points (mostly because the ability to detect single vessel disease or mild stenoses of 50-70% is not as good with stress Echo), can see defects in areas that contain scar and viable myocardium, acquisition of images is not operator dependent, in virtually 100% of patients diagnostic images are obtained, with Tc simultaneous assessment of perfusion and function is obtained, resting LV ejection fraction can be obtained, vasodilator SPECT has significantly higher sensitivity than vasodilator stress ECHO, dobutamine ECHO is associated with higher sensitivity and specificity than vasodilator ECHO.

• Longer imaging protocols, greater expense of equipment, must inject and store radiopharmaceuticals, inability to visualize the heart in real time, lower spatial resolution than ECHO, higher costs to patients.

In general, the sensitivity is lower for stress ECHO while the specificity is higher.

• 1 mm or more of horizontal or downsloping ST depression is associated with a poor prognosis
• Failure to achieve 6 METS is associated with an elevated mortality rate over the next 2.5 years.
• Failure of heart rate to rise is associated with higher mortality, even after adjusting for perfusion defects.
• Failure to reach 85% of age adjusted max HR is associated with a RR of 1.85 in mortality.
• Limitation of ETT is the fact that the magnitude of ST depression is not strongly associated with the extent of CAD
• Exercise testing alone has excellent prognostic ability among patients with atypical chest pain or non anginal pain who have a normal EKG at baseline. If these patients have a normal ETT, the prognosis is excellent.

• Nuclear Stress Myocardial Perfusion Imaging, often abbreviated MPI or MPS, is a technique for measuring perfusion of myocardial tissue using externally injected radioactive tracers. Photons, or positrons emitted from these tracers are then detected with specialized imaging equipment and software. The most common methods are single photon emission computed tomography (SPECT) and positron emission tomography (PET). SPECT can be performed with radiotracers based on thallium or technetium 99-m. PET is commonly performed with rubidium-82, although some centers use ammonia (NH3) or radiolabeled oxygen in water. Cardiac PET with fluorodeoxyglucose (FDG) is useful for other investigations such as evaluation of infections, sarcoidosis activity, and viability/hibernation. Flurpiridaz, is a PET tracer based on fluorine-18 (F-18) and was approved for use by the FDA in 2025.
• The following are associated with a poor prognosis:

  • 20% of the LV is a perfusion defect
  • Defects in more than one distribution suggestive of multivessel CAD
  • A large number of non reversible defects
  • Transient LV cavitary dilation
  • Increased lung uptake
  • Resting LVEF of < 40%

• Normal thallium: Mortality 1% per year
• Normal Tc: annual mortality 0.6%, 12 fold higher if there is a Tc defect
• The positive predictive value of stress myocardial perfusion imaging and stress ECHO is low: That is the percentage of people who die or sustain an MI is low among patients with abnormal findings. On the other hand the negative predictive value is high and exceeds 95%.

• Tl Imaging

  • Rest and delayed redistribution is the most common radionuclide method used to assess viability. Uptake of Tl is related not only to blood flow, but also to membrane integrity. Myocardial stunning or hibernation does not result in a reduction in Tl extraction as long as the sarcolemmal membrane does not sustain irreversible ischemic damage. 60 to 70% of asynergistic segments will show > a 50% improvement after revascularization.

• Tc Imaging

  • Same as above, as usual a better signal with Tc, can also assess regional wall thickening. If thickening is present, then viability is likely.

• PET

  • Considered by many to be the gold standard. Can be used to assess perfusion and metabolism simultaneously. If there is mismatch in perfusion and metabolism, then the tissue is viable. If there is a match, then there is scar.

Dobutamine: Enhanced systolic contractility with low dose dobutamine is associated with recovery.

Template:WikiDoc Sources CME Category::Cardiology

Editors-in-Chief: Eli V. Gelfand, M.D.[1], and Matthew W. Parker, M.D.[2] (Beth Israel Deaconess Medical Center, Harvard Medical School)

The plain film radiograph of the chest is the most commonly performed radiologic test, with approximately 150 million performed in the USA every year, accounting for 45% of all radiologic exams chestxraydotcom. Chest radiography is widely available, inexpensive, and carries low risk to the patient being examined. Therefore it is often the first test to image the heart and great vessels in patients with suspected cardiovascular disease, although much of the information about the cardiovascular system obtained from a chest x-ray is indirect and non-specific.

The test is performed by placing an x-ray film (or digital detector) parallel to the chest wall and then exposing the film to x-rays generated from a source on the opposite side of the patient’s body. The standard views most useful for evaluating cardiovascular structures are the postero-anterior (PA) view, in which the film is placed anterior to the chest and x-rays travel through the patient from posterior to anterior before reaching the film, and the antero-posterior (AP) view, in which the film is against the patient’s back and the x-ray generator is anterior to the patient’s body. The PA view places the heart closer to the x-ray film, resulting in less x-ray scatter and a more accurate representation of the cardiac size, but the AP view is often advantageous because it does not require any active participation from the patient and can be performed with a portable x-ray generator; that is, the film cartridge can be placed in bed behind a patient too unstable to travel to the radiology exam room and stand up in front of the x-ray apparatus. Because the plain-film is a 2-dimensional projection of the body, a lateral view, when feasible, is required to determine the location of structures along the AP axis of the body.

Fig. 1. PA Chest X-ray of a Normal Adult. Because the heart and other structures in the mediastinum have similar densities, there are only modest differences in their x-ray appearance. Thus, the most reliable information about the heart and vascular structures comes from the interfaces where they meet the aerated lung fields. Prior knowledge of the cardiovascular anatomy allows the interpreter to approximate the location of the heart structures and great vessels:

Fig. 2. PA Projections of Right Heart Stuctures. SVC is superior vena cava; PA are the pulmonary arteries, right and left; RA is right atrium; RV is right ventricle; and IVC is the approximate position of the inferior vena cava. The venae cavae are poorly visualized with plain film x-ray, however, the right border of the mediastinum is generally accepted as the right border of the SVC, which should not extend laterally beyond the right border of the heart in a normal individual. The RV is an anterior structure, so it is superimposed on the RA and left ventricule. Additionally, the interventricular septum lies obliquely in the body, so that its projection in this diagram is arbitrary.

Fig. 3. PA Projections of the Left Heart Structures. Ao is the aortic arch, which then continues as the descending aorta, indicated by the dotted line. LAu is the auricle of the left atrium, which itself sits posteriorly at the base of the heart. PV are the pulmonary veins converging on the left atrium. LV is the left ventricle, which is partially posterior to the right ventricle.

• Cardiac chamber dilation and hypertrophy

– Left ventricular hypertrophy

– Left atrial enlargement:

This radiograph of a patient with mitral stenosis shows a prominent left atrial appendage caused by pressure overload of the left atrium.

– Right ventricular/bi-ventricular hypertrophy

• Abnormalities of pulmonary vasculature

– mitral stenosis, pulmonary hypertension

• Heart failure

– examples of upper lobe vascular redistribution,

– Cardiogenic Pulmonary Edema

Radiograph of patient with congestive heart failure, showing pulmonary edema with Kerley lines and perihilar engorgement.

• Pericardial pathology

– pericardial effusion

First image, above, shows a patient with an enlarged, globular cardio-mediastinal silhouette representing a large pericardial effusion and a large right-sided pleural effusion one month after aortic valve replacement. The second image is the same patient after pericardiocentesis, which yielded one liter of pericardial fluid, and thoracentesis.

• Congenital cardiovascular anomalies

– Tetralogy – patent ductus arteriosus – coarctation of aorta – atrial septal defect – Eisenmenger syndrome

– Situs Inversus

This patient has situs inversus; the viscera including the heart developed in mirror-image fashion relative to their usual positions in the body. This can occur sporadically or as part of Kartagener’s syndrome.

• Cardiac fluoroscopy: Indications and procedural description

• Chest Imaging Tutorial at Michigan State University Department of Radiology
• Case-Based Introduction to Chest X-rays at the University of Liverpool School of Medicine.
• Overview of a systematic approach to reading Chest Radiographs at Everything2.
• Patient information about chest radiography from the American College of Radiology.

• Thoracic Imaging Information

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Editor(s)-In-Chief: C. Michael Gibson M.S., M.D. [1] Phone:617-525-6884 ; Eli V. Gelfand, M.D. [2]

• Echocardiography (echo) is a test that uses sound waves to create a moving picture of your heart. The picture shows how well your heart is working and its size and shape. There are several types of echo, including stress echo.

• Stress echo can show whether you have decreased blood flow to your heart, a sign of coronary heart disease. Another type of echo is transesophageal (tranz-ih-sof-uh-JEE-ul) echo, or TEE.

• TEE provides a view of the back of the heart. For this test, a sound wave wand is put on the end of a special tube. The tube is gently passed down your throat and into your esophagus (the passage leading from your mouth to your stomach). Because this passage is right behind the heart,

• Basic physical principles of ultrasound
• Quantification of pressure gradients
• Echocardiographic evaluation of ventricular dyssynchrony
• Echocardiography terminology
• Guidelines for echocardiography

• Transthoracic echo (TTE): standard views and measurements
• Transesophageal echocardiography (TEE): standard views
• M-mode echo: principles and classic findings
• Doppler echocardiography
• Tissue Doppler imaging
• Contrast echocardiography
• Stress echocardiography
• Three-dimensional echocardiography
• Myocardial contrast echocardiography
• Intraoperative echocardiography

• Echo in emergencies
• Echo in coronary artery disease
• Echo in pericardial diseases: effusion, cardiac tamponade, constriction
• Echo in dilated cardiomyopathies
• Echo in hypertrophic cardiomyopathy
• Echo in restrictive cardiomyopathies
• Echo in pulmonary hypertension
• Echo in pulmonary embolism
• Endocarditis (TTE and TEE)
• Echo in patients with atrial fibrillation
• Echo in cardiac tumors and masses
• Echo in diseases of the aorta
• Echo in congenital heart disease
• Echo in non-cardiac systemic disease

• Incidental cardiac findings on echocardiography
• Noncardiac findings on echocardiography

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Section editor: Eli V. Gelfand, M.D. (Beth Israel Deaconess Medical Center, Harvard Medical School) [1]

General overview of Nuclear Cardiology

• Basic physical principles of single-photon emission computed tomography (SPECT)
• Basic physical principles of positron emission tomography (PET)
• Commonly used radiopharmaceuticals
• Selecting appropriate candidates for myocardial perfusion imaging
• Standard exercise stress protocols
• Standard pharmacologic stress protocols
• Imaging protocols
• Combining myocardial perfusion imaging with coronary CT
• Radionuclide angiography
• Molecular imaging and related novel technologies

Clinical use of stress myocardial perfusion imaging (MPI)

• ACCF/ASNC appropriateness criteria for SPECT-MPI (2005)
• ACC/AHA guidelines for cardiac radionuclide imaging (2003)

Coronary Disease

• Assessment of patients presenting with chest pain to the Emergency Department
• Detection of CAD
• Management, risk assessment and prognosis of patients with chronic CAD
• Detection of acute MI
• Risk assessment of patients following ST-elevation MI
• Risk assessment of patients following non-ST elevation acute coronary syndrome

Heart Failure

• Assessment of LV systolic function
• Assessment of etiology of heart failure
• Detection of CAD in patients with heart failure
• Determination of myocardial viability

Specific patient populations

• Patients with an “uninterpretable” resting ECG
• Elderly patients
• Asymptomatic patients with diabetes
• Patients following up after a coronary calcium screening
• Patients before and after coronary revascularization
• Patients undergoing elective noncardiac surgery

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: coronary arteriography, cardiac arteriography, cardiac angiogram, coronary angio, coronary artery angio, coronary cath, cardiac cath

• Overview
• Historical perspective
• Contraindications
• Appropriate Use Criteria for Revascularization
• Complications
• Technique
• Film Quality

• Coronary arteries
• Left coronary artery | Left main coronary artery | Left anterior descending artery | Left circumflex artery | Ramus intermedius
• Right coronary artery
• Coronary artery dominance

• Separate ostia
• Anomalous origins of the coronary arteries
• Coronary artery fistula

• Standard angiographic views
• Left coronary artery
• Right coronary artery

• TIMI flow grade (TFG): TIMI flow grade 0 | TIMI flow grade 1 | TIMI flow grade 2 | TIMI flow grade 3
• TIMI frame count (TFC)
• Pulsatile flow
• Deceleration

• TIMI myocardial perfusion grade (TMPG): TIMI myocardial perfusion grade 0 | TIMI myocardial perfusion grade 0.5 | TIMI myocardial perfusion grade 1 | TIMI myocardial perfusion grade 2 | TIMI myocardial perfusion grade 3

• ACC-AHA characteristics of type A, B, and C coronary lesions
• SCAI Lesion Classification System

• TIMI thrombus grade: TIMI thrombus grade 0 | TIMI thrombus grade 1 | TIMI thrombus grade 2 | TIMI thrombus grade 3 | TIMI thrombus grade 4 | TIMI thrombus grade 5 | TIMI thrombus grade 6

• Quantitative angiography
• Definitions of Preprocedural Lesion Morphology
• Irregular lesion
• Disease extent
• Arterial foreshortening
• Infarct related artery (Culprit lesion)
• Restenosis
• Degenerated saphenous vein graft
• Collaterals
• Coronary artery ulceration
• Coronary artery aneurysm
• Coronary artery bifurcation
• Coronary artery trifurcation

• Technique
• Quantification of LV Function
• Quantification of Mitral Regurgitation
• Left Ventricular Ejection Fraction Assessment by Visual Estimation

Left Internal Mammary Artery

Risks stratification and benefits of PCI | Conscious Sedation | Preparation of the Patient for Diagnostic Catheterization | Technical Aspects of the Cardiac Catheterization Laboratory | Obtaining Venous and Arterial Access | Equipment Used in Diagnostic Cardiac Catheterizaiton | Hemodynamic Assessment in the Cardiac Catheterization Laboratory | Radiation Safety

Therapeutic procedures | Advances in catheter based physical treatments

Classification of the Lesion | The Calcified Lesion | The Ostial Lesion | The Angulated or Tortuous Lesion | The Bifurcation Lesion | The Long Lesion | The Bridge Lesion | Vasospasm | The Chronic Total Occlusion | Multivessel Disease | Distal Anastomotic Lesions | Left Main Intervention | The Thrombotic Lesion

Vessel Perforation | Dissection | Distal Embolization | No-reflow | Abrupt Closure | Restenosis | Late Acquired Stent Malapposition | Loss of Side Branch | Multiple Complications | Coronary stent thrombosis | Slow flow | Pulsatile flow | Deceleration | Ectasia | Intimal flap | Staining | Coronary air embolism

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Eli V. Gelfand, M.D.[2]; Caitlin J. Harrigan [3]

• CMR-Related Definitions
• ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 Appropriateness Criteria for Cardiac Magnetic Resonance Imaging
• ACR Practice Guideline for the Performance and Interpretation of Cardiac Magnetic Resonance Imaging (MRI)
• Basic MRI Physics
• CMR Image Acquisition Protocols
• Standard Image Orientation
• Normal Cardiac Anatomy as Viewed by CMR
• Contrast CMR
• Cine CMR
• Myocardial Tagging
• Flow Quantification by CMR
• CMR in Valvular Heart Disease

• CMR in Dilated Cardiomyopathy, Hypertrophic cardiomyopathy, myocarditis, amyloidosis, other infiltrative heart diseases and arrhythmogenic right ventricular dysplasia

• CMR in Cardiac Masses

• CMR in Pericardial Disease

• CMR in Congenital heart Disease

• CMR in Athlete’s Heart
• Coronary MRI
• Peripheral Vascular MRA
• Atherosclerosis/Plaque Imaging with CMR
• CMR Risk Factors: NSF
• CMR in Heart failure

• CMR in Coronary artery disease

• CMR in Ischemic heart disease

• CMR in Myocardial infarction

• CMR in Pulmonary angiography

• CMR in atrial fibrillation

• CMR in peripheral arterial disease

• CMR in Carotid artery disease

• CMR in thoracic aortic disease

• CMR in renal artery disease

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Editors-In-Chief: Joanna J. Wykrzykowska, MD; Alexander Morss, MD; Roger J. Laham, MD; Melvin Clouse, MD

• CT angiography is emerging as the imaging modality of choice to rule out significant coronary artery disease in patients with low pretest probablity of disease. Good negative predictive value of the test (Garcia et al., 2006) promises to obviate the need for cardiac catheterization in patients with atypical chest pain
• The entire coronary tree can be examine in one breath hold
• Temporal resolution is 100 ms allowing for almost motion free imaging in the diastolic phase
• Spatial resolution is determined by the so called pitch=travel/x-ray beam width which currently ranges between 0.25-0.5 mm
• 64 slice/detector scanner can cover in a helical fashion 12.5 cm in 5 secs; new 256 detector MDCT will allow single beat aquisition thereby reducing any motion artifact and reducing the radiation dose
• As the technology improves with new post-processing software MDCT may allow for non-invasive screening for in-stent restenosis, especially after left main stenting

• Electron Beam CT was developped in the 1980s
• It is performed before coronary CTA and if calcium score is above 1000, the CTA postion of the exam is aborted, due to inerpretable results
• EBCT and calcium score correlated with overall atherosclerosis burden and high calcium scores confer a 10 fold risk of future coronary events
• It is an independent risk factor of the Framingham Health Study Risk Score
• More importantly, calcium score progression on serial EBCT in the same patient confers the highest risk of future cardiac events
• Basic calcium score is calculated by simply adding the calcified areas slices by slice in each coronary artery examined

• Patient preparation (heart rate and breath hold)
  • Upper heart rate limits are 65 beats/min and thus beta-blockers IV and/or po need to be administered to achieve an optimal heart rate
  • Usual protocol is to give 100 mg of metoprolol for HR> 65 1 hour before the scan
  • For frequent PVCs IV lidocaine can be considered
  • If the patient has a pacer that should be interrogated before the scan
  • Usually 80 cc of contrast dye are needed for coronary imaging and 100 cc for SVG grafts with a 40-50 cc saline flush
  • The scan is triggered when a selected area in the aorta reaches a peak signal in Hounsfield Units (HU)
• ECG gating
• Spatial and Temporal resolution
• Basics of reconstruction: diagnostic qualty of the images largely depends on chosing the reconstruction time within the cardiac cycle; usually 60-70% of the RR interval is chosen
  • • axial images are usually not used primarily for detection of coronary stenosis but maybe used to confirm the findings from maximum intensity projections
    • MPR = multiplanar recoonstructions
    • MIP = maximum intensity projections: simulate three different cardiac catheter projections: MIP planes reconstructed along the atria-ventricular groove to create in the left anterior oblique projection show the left circumfelx and right coronary artery; MIP reconstruction along the interventricular groove in the right anterior oblique projection show the left anterior descending artery
    • VRT = volume rendering technique
• Hounsfield units:
  • Water = 0
  • Air and Bone = 1000

• Image processing and Post-processing
• Results from the 16 slice MDCT:

This randomized trial of 238 patients assessed 1629 coronary segments, of which 71% were evaluable. Detection of > 50% stenosis in the evaluable segments had a sensitivity: 89% specificity: 65% and 54% in a patient-based analysis positive predictive value: 13% negative predictive value: 99%

High percentage of non-evaluable segments and false positive results (low specificity and positive predictive value) in this study lead to the conclusion that MDCT 16 should not be used routinely for angiographic assessment. The main reasons for inability to evaluate the segments were respiratory or cardiac motion, excessive calcification, poor opacification and small vessel size (< 2 mm). This is after beta-blocker administration to optimize the heart rate and after exclusion of patients with calcium scores > 600. There were 10 false negative results. Out of the patients with non-evaluable segments 38% were found to have significant coronary artery disease on angiography (Garcia MJ et al. for the CATSCAN Study Investigators; JAMA 2006).

The multicenter trial Coronary Evaluation using 64-Row Multi-detector CT Angiography completed recently will show us the accuracy of 64-slice scanner in identifying significant stenosis.

• Stents: The major limitation of the MDCT has been in imaging of coronary stents due to partial volume effects and beam hardening. Accuracy of stent lumen analysis by the 4 and 16 slice scanner has been quite limited. However with sharp kernels and post-processing software on 64 slice scanners, stents 3.0 mm and greater appear to be possible to adequately evaluate.

Follow up of patients after multivessel stenting would greatly benefit from CTA technology. Particularly that in stent restenosis presents as non-ST elevation MI in 20% of cases. Recently published papers suggest that the technology may have improved accuracy. Cademartini et al. (JACC, 2007) evaluated 182 patients with previously placed stents. Only 14 segments in that study were unevaluable (7%).Of the 20 stents with significant in-stent restenosis by angiography, 19 were correctly identified by MDCT. This gave overall: sensitivity: 95% specificity: 93% positive predictive value: 63% negative predictive value: 99% To achieve these results tube voltage of 120 KeV was used and a sharp convulition kernel as well as particular window settings. While the readers were blinded to the angiographi results, they were aware of prior stenting history (? type of stent). Most importantly, unlike in the previous trials stents <3.0 mm, = 3.0 mm and >3.0 mm had comparable assessability and the rate of false positives was the same across the stent sizes. The trial did not comment specifically on stent type as predictor of assessability. We know from prior investigations that stents with thick struts and closed-cell stents such as Cypher stents tend to be more difficult to assess that thinner strut cobalt chromium or Taxus stents. These promising results await verification in a larger multicenter trial.

• Left main stents
• Bypass-grafts
• Chronic total occlusions and planning of interventions

• Perfusion imaging
• Valvular disease
• LV function

For 16 detector multi slice CTs the radiation dose is 8 m Sev which is 2-3 times that of coronary cardiac catheterization and comparable to the nuclear imaging dose. This is reduced with 64 slice scanner and will be further reduced with dual source and 256 detector scanners.

Similarly, given the 5 second acquisition rate for 256 slices scanners, contrast bolus dose will be further reduced to 40-60 ml.

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Editor-in-Chief: Thomas F. Heston, MD, PhD

Positron emission tomography (PET) is a nuclear medicine medical imaging technique which produces a three-dimensional image or map of functional processes in the body. The concept of emission and transmission tomography was introduced by David Kuhl and Roy Edwards in the late 1950’s. Their work later led to the design and construction of several tomographic instruments at the University of Pennsylvania. The technique was further developed by Michel (Michael) Ter-Pogossian, Michael E. Phelps and others at the Washington University School of Medicine ^[1][2]

To conduct the scan, a short-lived radioactive tracer isotope, which decays by emitting a positron, which also has been chemically incorporated into a metabolically active molecule, is injected into the living subject (usually into blood circulation). There is a waiting period while the metabolically active molecule becomes concentrated in tissues of interest; then the research subject or patient is placed in the imaging scanner. The molecule most commonly used for this purpose is fluorodeoxyglucose (FDG), a sugar, for which the waiting period is typically an hour.

As the radioisotope undergoes positron emission decay (also known as positive beta decay), it emits a positron, the antimatter counterpart of an electron. After travelling up to a few millimeters the positron encounters and annihilates with an electron, producing a pair of annihilation (gamma) photons moving in almost opposite directions. These are detected when they reach a scintillator material in the scanning device, creating a burst of light which is detected by photomultiplier tubes or silicon avalanche photodiodes (Si APD). The technique depends on simultaneous or coincident detection of the pair of photons; photons which do not arrive in pairs (i.e., within a few nanoseconds) are ignored.

The most significant fraction of electron-positron decays result in two 511 keV gamma photons being emitted at almost 180 degrees to each other; hence it is possible to localize their source along a straight line of coincidence (also called formally the “line of response” or LOR). In practice the LOR has a finite width as the emitted photons are not exactly 180 degrees apart. If the recovery time of detectors is in the picosecond range rather than the 10’s of nanosecond range, it is possible to calculate the single point on the LOR at which an annihilation event originated, by measuring the “time of flight” of the two photons. This technology is not yet common, but it is available on some new systems [1]. More commonly, a technique much like the reconstruction of computed tomography (CT) and single photon emission computed tomography (SPECT) data is used, although the data set collected in PET is much poorer than CT, so reconstruction techniques are more difficult (see section below on image reconstruction of PET). Using statistics collected from tens-of-thousands of coincidence events, a set of simultaneous equations for the total activity of each parcel of tissue along many LORs can be solved by a number of techniques, and thus a map of radioactivities as a function of location for parcels or bits of tissue (“voxels”), may be constructed and plotted. The resulting map shows the tissues in which the molecular probe has become concentrated, and can be interpreted by a nuclear medicine physician or radiologist in the context of the patient’s diagnosis and treatment plan.

PET scans are increasingly read alongside CT or magnetic resonance imaging (MRI) scans, the combination (co-registration”) giving both anatomic and metabolic information (i.e., what the structure is, and what it is doing biochemically). Because PET imaging is most useful in combination with anatomical imaging, such as CT, modern PET scanners are now available with integrated high-end multi-detector-row CT scanners. Because the two scans can be performed in immediate sequence during the same session, with the patient not changing position between the two types of scans, the two sets of images are more-precisely registered, so that areas of abnormality on the PET imaging can be more perfectly correlated with anatomy on the CT images. This is very useful in showing detailed views of moving organs or structures with higher amounts of anatomical variation, such as are more likely to occur outside the brain.

PET is both a medical and research tool. It is used heavily in clinical oncology (medical imaging of tumors and the search for metastases), and for clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias. PET is also an important research tool to map normal human brain and heart function.

PET is also used in pre-clinical studies using animals, where it allows repeated investigations into the same subjects. This is particularly valuable in cancer research, as it results in an increase in the statistical quality of the data (subjects can act as their own control) and substantially reduces the numbers of animals required for a given study.

Alternative methods of scanning include x-ray computed tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI), ultrasound and single photon emission computed tomography (SPECT).

While some imaging scans such as CT and MRI isolate organic anatomic changes in the body, PET scanners, like SPECT are capable of detecting areas of molecular biology detail (even prior to anatomic change). The PET scanner does this via the use of radiolabelled molecular probes that have different rates of uptake, depending on the type and function of tissue involved. The changing of regional blood flow in various anatomic structures (as a measure of the injected positron emitter) can be visualized and relatively quantified with a PET scan.

PET imaging is best performed using a dedicated PET scanner. However, it is possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence detector. The quality of gamma-camera PET is considerably lower, and acquisition is slower. However, for institutions with low demand for PET, this may allow on-site imaging, instead of referring patients to another center, or relying on a visit by a mobile scanner.

Radionuclides used in PET scanning are typically isotopes with short half lives such as carbon-11 (~20 min), nitrogen-13 (~10 min), oxygen-15 (~2 min), and fluorine-18 (~110 min). Due to their short half lives, the radionuclides must be produced in a cyclotron which is not too far away in delivery-time to the PET scanner. These radionuclides are incorporated into compounds normally used by the body such as glucose, water or ammonia and then injected into the body to trace where they become distributed. Such labelled compounds are known as radiotracers.

PET as a technique for scientific investigation in humans is limited by the need for clearance by ethics committees to inject radioactive material into participants. The minimization of radiation dose to the subject is an attractive feature of the use of short-lived radionuclides. Besides its established role as a diagnostic technique, PET has an expanding role as a method to assess the response to therapy, in particular, cancer therapy (e.g. Young et al. 1999), where the risk to the patient from lack of knowledge about disease progress is much greater than the risk from the test radiation.

Limitations to the widespread use of PET arise from the high costs of cyclotrons needed to produce the short-lived radionuclides for PET scanning and the need for specially adapted on-site chemical synthesis apparatus to produce the radiopharmaceuticals. Few hospitals and universities are capable of maintaining such systems, and most clinical PET is supported by third-party suppliers of radiotracers which can supply many sites simultaneously. This limitation restricts clinical PET primarily to the use of tracers labelled with F-18, which has a half life of 110 minutes and can be transported a reasonable distance before use, or to rubidium-82, which can be created in a portable generator and is used for myocardial perfusion studies. Nevertheless, in recent years a few on-site cyclotrons with integrated shielding and hot labs have begun to accompany PET units to remote hospitals. The presence of the small on-site cyclotron promises to expand in the future as the cyclotrons shrink in response to the high cost of isotope transportation to remote PET machines ^[3]

Because the half-life of F-18 is about two hours, the prepared dose of a radiopharmaceutical bearing this radionuclide will undergo multiple half-lives of decay during the working day. This necessitates frequent recalibration of the remaining dose (determination of activity per unit volume) and careful planning with respect to patient scheduling.

The raw data collected by a PET scanner are a list of ‘coincidence events’ representing near-simultaneous detection of annihilation photons by a pair of detectors. Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred.

Coincidence events can be grouped into projections images, called sinograms. The sinograms are sorted by the angle of each view and tilt, the latter in 3D case images. The sinogram images are analogous to the projections captured by computed tomography (CT) scanners, and can be reconstructed in a similar way. However, the statistics of the data is much worse than those obtained through transmission tomography. A normal PET data set has millions of counts for the whole acquisition, while the CT can reach a few billion counts. Furthermore, PET data suffer from scatter and random events much more dramatically than CT data does.

In practice, considerable pre-processing of the data is required – correction for random coincidences, estimation and subtraction of scattered photons, detector dead-time correction (after the detection of a photon, the detector must “cool down” again) and detector-sensitivity correction (for both inherent detector sensitivity and changes in sensitivity due to angle of incidence).

Filtered back projection (FBP) has been frequently used to reconstruct images from the projections. This algorithm has the advantage of being simple while having a low requirement for computing resources. However, shot noise in the raw data is prominent in the reconstructed images and areas of high tracer uptake tend to form streaks across the image.

Iterative expectation-maximization algorithms are now the preferred method of reconstruction. The advantage is a better noise profile and resistance to the streak artifacts common with FBP, but the disadvantage is higher computer resource requirements.

Attenuation correction: As different LORs must traverse different thicknesses of tissue, the photons are attenuated differentially. The result is that structures deep in the body are reconstructed as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray CT equipment, however earlier equipment offered a crude form of CT using a gamma ray (positron emitting) source and the PET detectors.

While attenuation corrected images are generally more faithful representations, the correction process is itself susceptible to significant artifacts. As a result, both corrected and uncorrected images are always reconstructed and read together.

2D/3D reconstruction: Early PET scanners had only a single ring of detectors, hence the acquisition of data and subsequent reconstruction was restricted to a single transverse plane. More modern scanners now include multiple rings, essentially forming a cylinder of detectors.

There are two approaches to reconstructing data from such a scanner: 1) treat each ring as a separate entity, so that only coincidences within a ring are detected, the image from each ring can then be reconstructed individually (2D reconstruction), or 2) allow coincidences to be detected between rings as well as within rings, then reconstruct the entire volume together (3D).

3D techniques have better sensitivity (because more coincidences are detected and used) and therefore less noise, but are more sensitive to the effects of scatter and random coincidences, as well as requiring correspondingly greater computer resources.

PET is a valuable technique for some diseases and disorders, because it is possible to target the radio-chemicals used for particular bodily functions.

1. Oncology: PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), called FDG-PET, is widely used in clinical oncology. This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly-growing malignant tumours). A typical dose of FDG used in an oncological scan is 200-400 MBq for an adult human. Because the oxygen atom which is replaced by F-18 to generate FDG is required for the next step in glucose metabolism in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the phosphate added by hexokinase. This means that FDG is trapped in any cell which takes it up, until it decays, since phosphorylated sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the brain, the liver, and most cancers. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin’s disease, non Hodgkin’s lymphoma, and lung cancer. Many other types of solid tumors will be found to be very highly labeled on a case-by-case basis– a fact which becomes especially useful in searching for tumor metastasis, or for recurrence after a known highly-active primary tumor is removed. Because individual PET scans are more expensive than “conventional” imaging with computed tomography (CT) and magnetic resonance imaging (MRI), expansion of FDG-PET in cost-constrained health services will depend on proper health technology assessment; this problem is a difficult one because structural and functional imaging often cannot be directly compared, as they provide different information. Oncology scans using FDG make up over 90% of all PET scans in current practice.
2. Neurology: PET neuroimaging is based on an assumption that areas of high radioactivity are associated with brain activity. What is actually measured indirectly is the flow of blood to different parts of the brain, which is generally believed to be correlated, and has been measured using the tracer oxygen-15. However, because of its 2-minute half-life O-15 must be piped directly from a medical cyclotron for such uses, and this is difficult. In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer’s disease greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to differentiate Alzheimer’s disease from other dementing processes, and also to make early diagnosis of Alzheimer’s disease. The advantage of FDG-PET for these uses is its much wider availability.

   Several radiotracers (i.e. radioligands) have been developed for PET that are ligands for specific neuroreceptor subtypes (e.g. dopamine D2, serotonin 5-HT1A, etc.), transporters (such as [(11)C]McN5652, [(11)C]DASB or other novel tracer ligands for serotonin in this case), or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses. A novel probe developed at the University of Pittsburgh termed PIB (Pittsburgh Compound-B) permits the visualization of amyloid plaques in the brains of Alzheimer’s patients. This technology could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies.

3. Cardiology, atherosclerosis and vascular disease study: In clinical cardiology, FDG-PET can identify so-called “hibernating myocardium“, but its cost-effectiveness in this role versus SPECT is unclear. Recently, a role has been suggested for FDG-PET imaging of atherosclerosis to detect patients at risk of stroke [2].
4. Neuropsychology / Cognitive neuroscience: To examine links between specific psychological processes or disorders and brain activity.
5. Psychiatry: Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. Radioligands that bind to dopamine receptors (D1,D2, reuptake transporter), serotonin receptors (5HT1A, 5HT2A, reuptake transporter) opioid receptors (mu) and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in schizophrenia, substance abuse, mood disorders and other psychiatric conditions.
6. Pharmacology: In pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals. The uptake of the drug, the tissues in which it concentrates, and its eventual elimination, can be monitored far more quickly and cost effectively than the older technique of killing and dissecting the animals to discover the same information. PET scanners for rats and apes are marketed for this purpose. The technique is still generally too expensive for the veterinary medicine market, however, so very few pet PET scans are done. Drug occupancy at the purported site of action can also be inferred indirectly by competition studies between unlabeled drug and radiolabeled compounds known apriori to bind with specificity to the site.

PET scanning is non-invasive, but it does involve exposure to ionizing radiation. The total dose of radiation is small, however, usually around 7 mSv. This can be compared to 2.2 mSv average annual background radiation in the UK, 0.02 mSv for a chest x-ray, up to 8 mSv for a CT scan of the chest, 2-6 mSv per annum for aircrew (data from UK National Radiological Protection Board).

In Canada, availability varies from province to province [3]. In Ontario, PET scan costs are not covered under the government-funded public health system (OHIP), but scans are available from a few public and private facilities at a cost equivalent of approximately $2500 USD. [4]

• Diffuse optical imaging

• Young H, Baum R, Cremerius U; et al. (1999). “Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations”. European Journal of Cancer. 35 (13): 1773–1782.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Bustamante E. and Pedersen P.L. (1977). “High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase”. Proceedings of the National Academy of Sciences USA. 74 (9): 3735–3739.
• Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergstrom M, Savitcheva I, Huang GF, Estrada S, Ausen B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, and Langstrom B. (2004). “Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B”. Annals of Neurology. 55 (3): 306–319.CS1 maint: Multiple names: authors list (link)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The following is a list of genetic disorders and their origins. Besides, most disorders are a code that indicates the type of fertilization and the chromosome involved.

• P – Point mutation, or any insertion/deletion entirely inside one gene
• D – Deletion of a gene or genes
• C – Whole chromosome extra, missing, or both – see chromosomal aberrations
• T – Trinucleotide repeat disorders – gene is extended in length