Cardiology Database

Biochemical markers of myocardial necrosis

2010-02-16T18:07:00.007+02:00

The Damage of myocytes results in release of several proteins into the circulation. The estimation of the serum level of these proteins can be used as a marker of myocardial necrosis. These proteins include:

Myoglobin
Creatine kinase (CK) and its isozyme myocardial band creatine kinase (CK-MB)
Cardiac troponins I and T (cTnI and cTnT)
Lactate dehydrogenase
Aspartate aminotransferase (AST) or (SGOT)
Ischemia modified albumin
Heart Fatty acid binding protein
Myosin light chain

The criteria for ideal biomarker for myocardial necrosis are:

High sensitivity: abundant in myocardial tissue.
High specificity: not present in extramyocardial tissues.
Rapid release from damaged cells
Cost effective detection
Can be detected precisely

Elevation of biochemical markers is essential for diagnosis of myocardial infarction. From the definition of myocardial infarction "it is the typical rise and fall of biomarkers of myocardial ischemia with at least a single value above the 99^th percentile of the upper reference limit, combined with the presence of any of ischemia symptoms, ischemic ECG changes (Q-waves, ST elevation or ST depression) or coronary intervention". However this definition considers only 2 of the cardiac biomarker, namely troponins and CK-MB. Due to the lag between the onset of chest pain and appearance of biochemical markers in blood, a second sample should be obtained and tested after 6 hours of the presentation before exclusion of myocardial infarction.

Myoglobin:

It is a small heme protein found in myocardium and skeletal muscles.
The earliest marker to rise (within 1-2 hours) because of its small molecular weight that facilitates its diffusion from the damaged tissue to circulation.
Peaks after 6-8 hours
Returns to normal after 24 hours
It is highly sensitive.
It is not specific to myocardium because it is found also in greater amounts in the skeletal muscles. So, not used in clinical practice to detect myocardial necrosis.
Normal level is 30-90 ng/ml in males and 10-55 ng/ml in females.

Creatine kinase (CK) and its isoenzyme (CK-MB):

It is found within the striated muscle (skeletal and cardiac) cells and is essential for ATP production (creatine phosphate shuttle).

It is a dimer formed of two subunits. In the skeletal muscle the two subunits are of M type. In the cardiac muscle there is one M subunit and the other is of B type.
The CK-MB isozyme is abundant in the cardiac myocytes (40%). The CK-MM isozyme is dominant in skeletal muscle (97%).
Detection of total CK is less sensitive and less specific than detection of CK-MB.
Both CK and CK-MB are elevated in other causes than MI, e.g. rhabdomyplysis. In such cases, CK-MB to total CK fraction of >10% is diagnostic of MI.
CK-MB is detectable after 4-6 hours of onset of chest pain in MI, peaks after 24 hours and remains elevated for 3-4 days.
CK-MB is more useful in detection of re-infarction because of its faster return to normal value as compared with troponins.
Normal CK: 15-170 U/L
Normal CK-MB: 0-15 U/L

Troponins:

Troponin complex is a regulatory protein responsible for regulation of myocyte contraction. It is formed of 3 subunits. Troponin C binds to the calcium, troponin T binds to tropomyosin and troponin I inhibits actin and myosin interaction.

The bulk of troponin is found within the contractile apparatus but a small fraction is found free in the cytoplasm (cytosolic) and it is the first part that detected in the plasma.
Normal cTnI is <0.1>
- It is elevated 4-6 hours after the onset of MI.
It peaks after 24 hours.
It remains elevated for 1-2 weeks after onset (TnT longer than TnI).
It is highly sensitive and specific for myocardial damage.
It adds prognostic value to the diagnosis as patients with negative troponins are considered of low risk. Also, the level of elevation is correlated to the risk. Patients with elevated troponins <6>
Troponins are not useful for diagnosis of re-infarction because it takes long duration to return to the normal value. So, concomitant estimation of CK-MB is needed.
Elevation of troponins with normal CK-MB levels identifies the patients who will gain greatest benefits of GP IIb/IIIa inhibitors.

other conditions that cause elevation in cardiac troponins are:

- other causes of cardiac injury:

cardiac contusion

Pulmonary embolism

Acute decompensated heart failure

Coronary spasm

Hypertensive crisis

Myocarditis

DC cardioversion/defibrillation/ablation procedures

- Renal failure: elevated troponins level is found in high percentage of asymptomatic patients with end stage renal disease. cTnI is much more specific than cTnT in this group of patients.

- Other infrequent causes:

Subarachnoid hemorrhage and cerebrovascular accidents.

Endocrinal diseases.

Hematological malignancies.

Skeletal muscle diseases: dermatomyositis and polymyositis.

Sepsis

Lactate dehydrogenase (LDH):

This enzyme is widely distributed in many tissues and organs.
It is not specific for myocardial injury as it is found also in RBCs WBCs, lungs, kidneys, liver, skeletal muscles, pancreas, placenta and other tissues.
It is elevated in MI after 24 hours, peaks after 3-4 days and returns to normal after 14 days.
The isoenzyme LDH₁ is the form found in cardiac myocytes and RBCs. Normally LDH₂ is the abundant form. So, flipped LDH pattern (LDH₁>LDH₂) is found in MI and hemolytic and megaloblastic anemias.
Normal LDH range: 100-225 U/L

Aspartate aminotransferase (AST also SGOT):

This enzyme is found in myocardial cell, skeletal muscle cells and liver cells. It is elevated in injury to any of these tissues, so, it is not specific to myocardial injury.
In MI, the AST level is increased after 6-8 hours of onset, peaks after 24 hours and returns to normal within 5-7 days. The AST level reaches 4-10 times the upper limit of normal in MI.
The normal value is 5-30 U/L.

Heart Fatty acid binding protein (H-FABP):

It is a small protein (14.5 KDa) responsible for transport of hydrophobic long chain fatty acids from cell membrane to mitochondria. The H-FABP is immunologically different from the corresponding protein found in liver and intestines.
It is released rapidly (1-3 hours) and appears early in urine. Its urinary level correlates to the extent of infarction.
It peaks at 6-8 hours from onset.
It returns rapidly to normal level after 24-36 hours (excellent for detection of re-infarction and perioperative infarction).

Myosin light chain 1 (MLC1):

Myosin is a part of the sarcomere (the basic contractile unit of the skeletal and cardiac muscles).
Myosin is heteropolymer formed of 2 heavy chains and 2 pairs of light chains. There are 2 types of myosin light chains: MLC1 and MLC2.
MLC2 is very labile and can not be measured clinically. Thus, it is not clinically significant.
MLC1 appears after 3-6 hours and peaks after 4 days. It remains elevated for 10-14 days.
Its peak level correlates to the infarction size and prognosis.
It can not be used as a marker of reperfusion or re-infarction.

Ischemia modified albumin (ILA):

Albumin loses its ability to bind some metals such as cobalt, after exposure to ischemic myocardium due to some conformational changes to its N-terminus.
This test poorly discriminates between myocardial ischemia with and without infarction.

N.B.: The normal levels mentioned above may vary with different methods of estimation and between different populations.

Carotid sinus massage

2010-02-08T16:50:00.004+02:00

Carotid sinus massage (CSM)

It is a vagal maneuver with diagnostic and therapeutic values.

How to do CSM?

- The patient is placed in supine position with neck extended by a pillow under his shoulders. The head is turned away from the side to be massages.

- Palpate the carotid artery pulsation at the angle of the mandible.

- Auscualtate the artery to be massaged looking for bruit.

- While monitoring ECG, apply gentle pressure with rolling from side to side for no more than 5 seconds. The artery is pressed aganist the transverse process of the opposite cervical vertebra.

- The test can be repeated on the opposite side but never do the test on both sides simultaneously.

Effects of CSM:

- cardioinhibitory response: decreasing both sinus rate, atrial rate and AV-nodal conduction.

- Vasodepressor response.

Value of CSM:

A) Diagnostic:

- In arrhythmias: Termination of arrhythmia indicates that in involves the AV node as a part of its reentry circuit (i.e. AV node dependent tachycardia) such as AVNRT and AVRT. In other supraventricular tachycardias, the heart rate will slow down temporarily due to the increase of the AV nodal block. This slowing of ventricular response may reveal hidden flutter waves or abnormal P waves in cases of atrial tachycardias. Gradual and temporary decrease of heart rate occurs with sinus tachycardia. Abrupt and temporary decrease of the heart rate occurs with atrial tachycardias. There will be no effect in ventricular tachycardias. In ventricular tachycardia with retrograde atrial activation, the CSM will cause the retro grade P waves to disappear or to decrease in frequency (due to increased V-A block). (Thanks to my dear colleague, Dr. Mohammed Saber for adding the last sentence).

- In syncope: inducibility of the syncope by CSM is very important unless there is another clear cause. Blood pressure should be monitored during the test. The protocol is different from the above mentioned. A sinus pause of 3 seconds or more, or a drop in blood pressure of 50 mmHg or more are diagnostic of cardotid sinus hypersensitivity.

- In ACS: relieve of chest pain by CSM is diagnostic for angina pectoris (Levine's test). This can be applied also for several minutes. Also, in the presence of LBBB, CSM may cause disappearance of the LBBB and reveal underlying ST elevation.

B) Therapeutic:

- CSM can be used for termination of AVNRT and AVRT.

- CSM may be applied for several minutes to treat acute pulmonary edema with hypertension and myocardial ischemia.

When not to do CSM?

- In patients with know or highly suspected carotid artery disease such as patients with history of stroke or TIA's or carotid artery bruit.

- Patients with previous unfavorable outcome with CSM.

- Be very cautious with elderly patients.

N.B.: The CSM may provoke exaggerated response in cases of digitalis toxicity, even before any other sign of toxicity.

Is IST a form of dysautonomia?

2009-12-03T20:13:00.003+02:00

IST = inapropriate sinus tachycardia

Back in the 19th century, there used to be a condition called “neurasthenia”. Young women (the beautiful but delicate ones, according to the romance novels of the time) would find themselves suddenly unable to function due to a host of inexplicable symptoms, often including fatigue, weakness, strange pains, dizziness, and passing out. Doctors would not find anything to explain these symptoms, so they were attributed to a “weak nervous system”, or neurasthenia. Victims were often confined to their beds, where they would either recover or, eventually (and tragically) die. And while nobody knew what caused this condition, everyone —doctors and laymen alike—took it seriously; the condition and its sufferers were treated with great respect.

Today’s doctors shake their heads in wonder at the notion of such a condition, and tend to put neurasthenia in the same bucketas the witchcraft hysteria of a few centuries earlier. But patients who would have been called neurasthenics 150 years ago are still around; they’re just given different labels. These labels include chronic fatigue syndrome (CFS), vasovagal or neurocardiogenic syncope, panic attacks, anxiety, irritable bowel syndrome (IBS), postural orthostatic tachycardia —and, quite possibly, IST. While most syndrome (POTS), fibromyalgia doctors still tend to think of these various syndromes as stand-alone conditions, they are all part of a general class of conditions called the dysautonomias.

In dysautonomia the autonomic nervous system loses its normal balance, and at various times the parasympathetic or sympathetic systems inappropriately predominate. Symptoms can include frequent, vague but disturbing aches and pains, faintness or frank syncope, fatigue and inertia, severe anxiety attacks, sinus tachycardia, hypotension, poor exercise tolerance, gastrointestinal disturbances, sweating, dizziness, blurred vision, numbnessand tingling, anxiety and (quite understandably) depression.

Sufferers of dysautonomia can experience all these symptoms or just a few of them. They can experience one cluster of symptoms at one time—and another at other times. And since people with dysautonomia are usually normal in every other way, a physical exam most often does not reveal any abnormalities. Patients are often labeled hysterical and are accorded little of the respect they received during the 19th century. (Fortunately, doctors no longer prescribe bed rest, so the risk of mortality is now very low.) When patients do get an actual diagnosis, the one they receive does often depend on their recently dominant symptoms and on which specialist they are referred to.

What causes dysautonomia? The dysautonomias do not have a single cause. Some patients inherit the propensity to develop dysautonomia syndromes, and variationsof dysautonomia often run in families. Viral illnesses can trigger a dysautonomia syndrome. So can exposure to chemicals. (Gulf War Syndrome is, in effect, dysautonomia—low blood pressure, tachycardia, fatigue and other symptoms—that, government denials aside, appears to have been triggered by exposure to toxins.) Dysautonomia can result after various types of trauma, especially trauma to the head and chest. (It has been reported to occur for example after breast implant surgery.) Dysautonomias caused by viral infections, toxic exposures, or trauma often have a rather sudden onset. CFS, for instance, most classically begins following a typical viral-like illness (sore throat, fever, muscle aches, and so on), but any of the dysautonomia syndromes can have a similar onset.

Is IST one of the dysautonomias? Obviously we do not know for sure, but it certainly shares many of the characteristics of dysautonomia, including that its onset is frequentlypreceded by a viral illness or trauma; that the patient profile is typical; and that “extra” symptoms frequently occur which are consistent with other forms of dysautonomia. (Indeed, many IST patients might have beenlabeled as suffering from IBS, POTS or CFS if they had seen someone other than an electrophysiologist.) Further, the fact that something stimulates the successfully ablated SA nodes to regenerate in IST patients suggests a more systemic problem than intrinsic SA nodal disease. And finally, electrophysiologists have noted that symptoms consistent with dysautonomia often persist even after successful SA nodal ablation (i.e., during the period of time that normal heart rates have been restored).

From: Richard N. Fogoros, Electrophysiologic testing, 4th ed.,2006.

Assessment of the Left ventricular function in the presence of mitral regurge

2009-11-29T10:37:00.006+02:00

The assessment of the rate of rise of LV pressure (dP/dt) can predict the intrinsic left vemtricular systolic function in a load-independent from. Thus it can be used in the assessment of left ventricular systolic function in the presence of mitral regurge. In fact, this method is under utilized in the daily practice.

To take this measure you must have good picture of the maximum regurgitant jet. Then take a continuous wave doppler spectral profile with high sweep speed (100mm/sec or more). Then measure the time taken for the velocity to rise from 1m/sec to 3m/sec. From Bernolli equation: the pressure change in this time is 32mmHg (4(3)² – 4(1)² = 36 – 4 = 32). Then dP/dt = 32/the measured time in seconds. Normally this value is > 1200. A dP/dt value from 800-1200 suggests mild systolic impairment. A dP/dt value <800>

LV systolic function	dP/dt	Time taken by LV to generate 32 mmHg
Normal	>1200	<27 msec
Mild-moderate impairment	800 – 1200	27 – 40 msec
Sever impairment	<800	>40 msec

(click on the images to view full size)

The major advantage of this method is that it is independent from changes in the afterload as the measures are taken in the isovolumetric contraction phase (before the opening of the aortic valve. Also, this method is well-validated in comparison with cardiac catheterization results. Unfortunately this method is unreliable in cases of left ventricular dysynchrony as in cases of LBBB. Also, it is affected by left atrial compliance. So, it can not be used in cases of acute mitral regurge as the left atrial pressure is elevated and the left atrium is noncompliant. If the regurgitant jet is eccentric, excess care should be taken to make the cursor line at the direction of the jet and at its center to avoid false measurements. However sever aortic stenosis and systemic hypertension was found to affect the reliability of this method.

The dP/dt was found to have prognostic value in the course of chronic heart failure. It is also used to predict the postoperative left ventricular function before valve repair and replacement.

The same principle can be used in the assessment of the right ventricular systolic function with some modification. On the tricuspid valve the time is measured time interval is between the velocities 0 and 2 m/sec (due to the lower pressures on the right side). Thus the dP/dt value on the right side is calculated by dividing 16 on the time interval taken to raise the tricuspid regurge velocity from 0 to 2 m/sec. But this method is not well-validated to assess RV systolic function.

On the opposite side the –ve dP/dt, which is the rate of decline of left ventricular pressure, can be used as a measure for diastolic dysfunction.

References:

1- http://www.criticalecho.com/content/tutorial-5-assessment-lv-systolic-function

2- Feigenbaum's Echocardiography, 6th Edition

3- Echocardiography: the normal examination and echocardiographic measurements, by Bonita Anderson 2002.

4- The practice of clinical echocardiography, by Catherine M. Otto‏, 2007

5- Echocardiography Review Guide, by Catherine M. Otto and Rebecca Gibbons Schwaegler, 2007

6- Doppler-derived dP/dt and –dP/dt predict survival in congestive heart failure, Theodore J. Kolias, Keith D. Aaronson, and William F. Armstrong, 2000;36;1594-1599 J. Am. Coll. Cardiol.

7- A new method for estimating left ventricular dP/dt by continuous wave Doppler-echocardiography. Validation studies at cardiac catheterization, GS Bargiggia, C Bertucci, F Recusani, A Raisaro, S de Servi, LM Valdes-Cruz, DJ Sahn and L Tronconi, 1989;80;1287-1292 Circulation

Systolic and diastolic currents of injury

2009-09-13T16:18:00.007+02:00

Why and How myocardial ischemia causes the ST segment changes?

Did you ask yourself this question before?

To answer such a question you need to go back to the physiological basics of electrocardiography. You must remeber that the ECG is the surface recording of electrical changes caused by electrical activity of the heart. At the culluar level those electrical changes are known as the action potential, which represents the potential differences across the cellular membrane as a result of a proper stimulus. The ischemia causes less negative resting membrane potential and loewr amplitude and longer duration of the action potential.

The ischemia is affecting a localized area and the rest of the myocardium is healthy and has normal action potential. This generates an electrical difference between the ischemic myocardium and the nearby healthy myocardium.

Systolic injury current:

During electrical systole (QT interval) the ischemic myocardium is less positive than the healthy myocardium (due to less amplitude of the action potential. This causes the electrical current to run from the healthy myocardium (more positive) to the ischemic myocardium. This is known as the systolic injury current. It is reflected in the ECG tracing as ST-segment elevation or depression according to the thickness and location of the ischemic area. If the ischemia affects the subendocardial area then the systolic injury current will be running from epicardium towards the endocardium (i.e. away from the body surface). The result will be ST-segment depression in the ECG leads corresponding to the ischemic territory. If the injuried area is whole thickness (transmural), then the systolic injury current will be running from the neighboring healthy myocardium towards the injured area. The summation vector of the resultant current will be directing outwards and causes ST-segment elevation in the leads representing the affected area.

Diastolic injury current:
The theory of diastolic current of injury is somewhat different. It is based on the fact that the resting membrane potential in the ischemic area is less negative in comparison with the healthy areas. This generates the diastolic injury current during the electrical diastole (TQ-interval). The direction of this current is from the ischemic area towards the healthy area. Thus it causes elevation of the TQ-segment in case of subendocardial infarction and depression of of TQ-segment in transmural infarction. But the TQ-segment is representing the base line for the ECG recording. So the net result will be apparent ST-segment depression and elevation respectively.

Images are from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed.

Smoking paradox

2009-09-12T06:17:00.005+02:00

Do you know about smoking paradox?

I first heard of this was during a clinical round a week ago. The professor asked us about it and nobody knew the answer. He told us the answer. It was noted that the incidence of in-stent stenosis following PCI was lower in smokers than non-smoker. He explained that by activation of CYP450 by smoking. This enzyme is responsible for transformation of clopidogrel to its active form. This lowers in-stent thrombosis and also lowered clopidogrel resistance.

However I have done my own search on the web to know more about that topic. I found some additional information. There are more explanations not mentioned by our professor. One explanation is the younger age of smokers in the studies revealing that paradox. Another one is the relectunce of smokers toseek medical advice when such problems occur. However, the long term mortality is still higher in smokers despite this claimed paradox.

I found two other paradoxes related to smoking. One was the lower mortality of somkers hospitalized for heart failure in OPIMIZE-HF study compared with non-smokers. However, the age of the smokers in the study was also younger, and this may be a resonable explanation. Another explanation is the difference in drug handling by smokers due to enzyme induction and inhibition. The third paradox related to smoking was noted in the study of lung cancer. It was noted the Japanese population has lower incidence of lung cancer compared with western populations, despite the higher incidence of smoking in the Japanese. This time the explanations were multiple. The main explanations were genetic difference, the different cigarette types and different filters, and the more healthy lifestyles led by the Japanese (less fat and less alcohol consumption).

The term "Paradox" may be deceiving or misleading. It gives the false impression that smoking is benfitial in this disease. The fact is exactly the opposite. Smoking causes the disease process to happen in an earlier age. And the real cause for the paradox is the younger age of the smokers, not the smoking itself, I guess. However it is still established that nonsmokers have longer and more healthy lives.

If you would like to read in more details follow these links:
1, 2 and 3.

Another case

2009-06-06T21:27:00.002+03:00

Here is another case met by our hospital few weeks ago. The patient is a 25 year old male admitted to our hospital because of comminuted fracture of the humerus in a motor vehicle accident and internal fixation by plate and screws was done. 2 days after operation, the patient suffered of dyspnea and tachypnea of sudden onset. His blood pressure was 80/40 and heart rate was 145 bpm. He was transferred to the ICU. His oxygen saturation was low (in 80's) and the chest exam revealed generalized sibilant rhonchi. The followinf ECG was obtained.

Pulmonary embolism was suspected but, unfortunately there was no availible CT or echocardiography in our hospital by that time. The attending physician thought he might loose the patient if he referred him to another hospital because the patient's condition was getting worse despite i.v. fluids oxygen inhalation and bronchodilators. He decided to give thrombolytic therapy. After receiving the streptokinase the patient's condition improved markedly. Here is the ECG obtained after finishing streptokinase infusion.

A case of arrhythmia

2009-05-26T01:56:00.007+03:00

50-year old male patient came to our hospital complaining of palpitations. He had steted that the onset was about 45 minutes ago and was relater to a fall from a ladder. The patient showed no dyspnea or chest pain. He was not on any medications. There was no signs of distress. His BP was 100/60 and heart rate was 140 bpm and irrregularly irregular. 12-lead ECG was done and here it is:
Click on it to enlarge

What do you thin is the diagnosis and what should we do?

Update: see the tracing after cardioversion below

Uncommon case of chest pain CME on medscape

2009-05-15T18:28:00.003+03:00

Here is a new CME case from CME medscape.
It is a nice case of chest pain due to an uncommon cause. Just try to guess the answer without looking at the multiple choices at the bottom and see if you can expect it. Look carefully in the X-ray. The link is here.

http://cme.medscape.com/viewarticle/702661

Statins

2009-05-14T11:02:00.012+03:00

Members:

- Atorvastatin
- Lovastatin
- Fluvastatin
- Pravastatin
- Simvastatin
- Rosuvastatin

Chemistry:

Simvasatin and Lovastatin are prodrugs containing lactone ring which is hydrolysed in the GIT into beta-hydroxy derivatives. Pravastatin is active as given as it has an open lactone ring.
Atorvastatin, Fluvastatin and Rosuvastatin are fluorine containing cogeners and are also active as given.

Pharmacokinetics:

Absorption: variable from 40 - 75 %. Only Fluvastatin is absorbed 100%. All members are susciptible to 1st pass metabolism.

Excretion: Mainly hepatic excretion in bile. Only 5 -20 % are excreted in urine.

Half-life: Atorvastatin and Rosuvastatin have relatively long half-lives (14 and 19 hours respectively). Others agents have short half-lives (1-3 hours).

Mechanism of action:

Competetive inhibition of the enzyme HMG-CoA reductase, which is the key enzyme in cholesterol synthesis (it catalyzes the rate limiting reaction). This causes marked reduction in LDL-cholesterol level, elevation of HDL-cholesterol level and slight reduction in triglycerides level.

There is also some other actions (most are of unknown mechanisms) that do not depend on the lipid lowering effect of statins. These are called "pleotropic" actions and they include:

inhibition of the inflammatory response.
improvement in the endothelial function.
platelet stabilization.
fibrinogen lowering effect

Adverse effects:

GIT disturbances: in the form of nausea, abdominal colic, diarrhea or constipation and flatulence.
Headache.
Pruritus.
Fatigue, myalgia or even myopathy can occur with statins. It is advisable to do CK level and stop statin if the level is 10-times the normal. The addition of oral coenzyme Q10 may decrease the symptoms. If the patient has developped myopathy, stop the statins and rechallenge later on with lower dose. It may be preferable to shift to Simvastatin or Fluvastatin which has lower incidence of myopathy. If the symptoms recurred, statins should be avoided and non-statin lipid modifying drugs are used instead.
Liver damage: it is a serious but rare side effect. transaminase level should be measured before starting treatment and after 3 months of initiation of statins. Later on, semiannual liver enzymes are advised. Elevation of liver enzymes to 3-folds the baseline is an indication to stop statins.
Drug interactions: Pravastatin and Fluvastatins are not metabolized by ctochrome oxidase P450, so, they are not susciptible to major drug interactions. Other agents are dependent on this enzyme for their metabolism. Enzyme inhibitors increase the risk of myopathy when used with such statins. Examples of those enzyme inhibitors are: erytheromycin, azole antifungals, cimetedine, methotrexate, cyclosporin, gemfibrozil, verapamil and amiodarone.

Indications:

Secondary prevention of coronary heart disease and cerebrovascular disease.
Treatment of some dyslipidemias such as:

- primary hypercholesterolemia
- mixed dyslipidemias
- homozygous familial hypercholesterolemia
- selected cases of heterozygous familial hypercholesterolemia

Contraindications:

Pregnancy and lactation: statins should not be given even to those women planning to get pregnant (statins should be stopped 6 months before getting pregnant).
Active liver disease.
Mypathies.

The following table summarizes the dosing of different statins:

Click on table to view

Mitral valve . . . Where did this name come from?

2009-05-13T23:48:00.006+03:00

Have you asked yourself this question. Why the left atrioventricular valve (or the bicuspid valve as some old books say) is commonly known as the mitral valve. In fact the name mitral is now the most commonly use name and it may sound strange somewhat if you use any either of the other 2 forementioned names. Then what does mitral mean. The word "mitre" is used to name the hat worn by catholic bishops and cardinals in ceremonies. Here is some mitre.

When you turn the open mitral valve upsidedown you will find it looking like the mitre. They say a picture worth 1000 word, so let us save the words. Here is the piture.

Lipoprotein Metabolism

2009-04-20T03:07:00.007+02:00

Lipoprotein Metabolism

Basic definitions and terms:

- Lipoproteins: complex compounds formed of lipids bound to proteins to facilitate the transfer of lipids between different tissues.

- Apoproptein: (also called apolipoprotein) the protein ingredient of lipoproteins.

- Integral protein: it is an essential component protein which is penetrating through the whole thickness of the phospholipid layer of lipoprotein particle. Examples: apoA, apoB100 and apoB48.

- Peripheral protein: surface protein component of the lipoprotein which can be exchanged between different types of lipoproteins and act as enzyme activator or receptor binding site.

- Centrifugal transport: transport of lipids from liver to the peripheral tissues, e.g. adipose tissue and muscles.

- Centripetal transport: transport of lipids from peripheral tissues to the liver.

Chylimicrons:

Synthesis: in the epithelial cells of the small intestines (enterocytes)

- The lipid component is synthesized from the absorbed dietary fatty acids, monoacyl glycerol and cholesterol.

- The apolipoprotein part (apoB48 and apoA) is synthesized in the rough endoplasmic reticulum by the ribosomes.

- The assembly of lipids with apolipoproteins takes place in the Glogi apparatus then they are packed into secretory vesicles where they are secreted by exocytosis into the intercellular space.

- The chylimicrons in this form are called nascent and are drained into the lacteals. They reach the thoracic duct and enter the venous circulation where they receive apoC and apoE from HDL to become mature chylimicrons.

Structure: mature chylimicrons are about 1µ in diameter and consist of 2% proteins (apoB48, apoA. apoC and apoE) and 98% lipids (mainly triglycerides).
Fate: the mature chylimicrons reach the peripheral tissues (adipose tissue and skeletal and cardiac muscles) where they are acted upon by the enzyme plasma lipoprotein lipase (LPL) which needs apoCII for its activation. This enzyme is present anchored with heparin sulfate to the capillary endothelium of the fore mentioned tissues. The action of this enzyme results in hydrolysis of triglycerides into glycerol and free fatty acids. The fatty acids are taken up by the cells in these tissues and are either used in the production of energy (skeletal and cardiac muscles) or used in the synthesis of tissue or milk fat (adipose tissues and lactating mammary glands. After losing the main bulk of its triglycerides, the chylimicrons returns the apoA and apoC back to the HDL and become chylimicron remnants. These particles give most of the remaining triglycerides to the HDL in exchange for cholesterol esters by means of CETP (cholestryl ester exchange protein also known as apoD). Then they are recognized by the liver through their apoE component and become endocytosed by the liver cells where they are hydrolyzed into amino acids, cholesterol and fatty acids.
Function: transport of the absorbed dietary (exogenous) triglycerides to the tissues. They also transport dietary cholesterol and fat soluble vitamins to the liver.

N.B's:

- Plasma lipoprotein lipase is called clearing factor because it clears the plasma from its turbidity caused by the presence of chylimicrons.

- Plasma lipoprotein lipase is activated by insulin and heparin.

- The chylimicrons are called so because they are 1µ in diameter and present in lymph (chyle).

- ApoB48 is encoded by the same gene for apoB100 with the addition of termination code to the mRNA by RNA editing enzymes. It has 48% of the molecular weight of apoB100.

- The neonatal liver has the enzyme LPL.

- Normally chylimicrons can not be detected in the plasma in the fasting state (>12 hours after meals).

Very low density lipoproteins (VLDL):

Synthesis: in the liver cells (hepatocytes)

- The triglyceride component is synthesized de novo or by re-esterification of free fatty acids.

- The apolipoprotein (apoB100) is synthesized in the microsomes.

- The VLDL in this form is called nascent and is secreted into the sinusoids. They venous circulation where they receive apoC and apoE from HDL to become mature VLDL.

Structure: VLDL consists of 10% proteins (apoB100, apoC and apoE) and 90% lipids (mainly triglycerides).
Fate: the mature VLDL reaches the peripheral tissues (adipose tissue and skeletal and cardiac muscles) where it is acted upon by the enzyme plasma lipoprotein lipase (LPL) which needs apoCII for its activation. The action of this enzyme results in hydrolysis of triglycerides into glycerol and free fatty acids. The fatty acids are taken up by the cells in these tissues and are either used in the production of energy (skeletal and cardiac muscles) or used in the synthesis of tissue or milk fat (adipose tissues and lactating mammary glands. After losing the main bulk of its triglycerides, the VLDL returns the apoC back to the HDL and become VLDL remnants (IDL). These particles give most of the remaining triglycerides to the HDL in exchange for cholesterol esters by means of CETP (cholestryl ester exchange protein also known as apoD). Then VLDL remnants give their apoE back to the HDL and become LDL.
Function: centrifugal transport or the endogenous triglycerides.

Low density lipoproteins (LDL):

Synthesis: LDL is formed of IDL (VLDL remnants) after exchange of triglycerides for cholesterol ester with HDL and loss of apoE.
Structure: LDL consists of 20% proteins (apoB100) and 80% lipids (mainly cholesterol).
Fate: the LDL binds to specific LDL receptors in the liver and peripheral tissues, then it is uptaken and hydrolyzed to give cholesterol.
Function: important source of cholesterol for peripheral tissues.

High density lipoproteins (HDL):

Synthesis: HDL is synthesized in the cells of liver and small intestine as discoidal HDL.
Structure: HDL consists of 32-55% proteins (apoA, apoC, apoE and apoD) and 45-68% lipids (phospholipids and cholesterol).
Fate: the HDL receives free cholesterol from tissues. This cholesterol may get esterified with fatty acids by means of LCAT (licethine cholesterol acyl transferase). The cholesterol esters are stored between the phospholipid bilayer transforming discoidal HDL to spheroidal HDL. Later on cholesterol esters may be given to chylimicron remnants or VLDL remnants in exchange for triglycerides by means of apoD (CETP cholesterol ester transfer protein).
Function: - centripetal transport of cholesterol (reverse cholesterol transport pathway).

- reservoir for apoE and apoC needed for maturation of chylimicrons and VLDL.

Pathology of cardiomyopathy

2009-03-09T12:58:00.011+02:00

While I am preparing for my master degree exam - 1st part, I noticed the topic of cardiomyopathy is much frequently encountered in pathology exams. I also noticed that our Egyptian pathology books are very deficient when dealing with this important topic. So, I decided to write it myself collecting data from different Pathology texts. It was "Robin's basic pathology, 8th ed" which I found most informative and well-organized and most of data here are derived from it.

Cardiomyopathy

Definition

Group of diseases that primarily involve the myocardium and produce myocardial dysfunction (or intrinsic disease of the cardiac muscle)

Types of cardiomyopathy

1. Dilated (congestive)

2. Hypertrophic

3. Restrictive

click image to enlarge

Dilated cardiomyopathy

Epidemiology

Incidence: Most common cardiomyopathy (90% of cases)

The incidence of this disorder in Europe and North America is 2-8 cases per 100 000 per year. The median age at presentation is about 50 years but young adults may be affected.

Etiology:

Idiopathic (most common)
Genetic causes (25-35%)
Myocarditis (usually postviral myocarditis with coxsackievirus B)
Toxic: e.g., doxorubicin(adriamycin), cocaine and cobalt.
Postpartum state
Alcoholism:can cause thiamine deficiency in addition to the acetaldehyde (alcohol metabolite) which is toxic to the myocardium.

Pathophysiology

Decreased contractility with a decreased EF (<40%)>
Systolic dysfunction type of left ventricular failure

Gross picture:

Global enlargement of the heart (the heart is 2-3 times the normal size and flobby)

All chambers are dilated.
Echocardiography shows poor contractility and mural thrombi may be present.
No significant 1ry valvular disease (except for functional regurgitation 2ry to ventricular chamber enlargement)
No significant affection of the coronary arteries.

Microscopic picture:

The histologic abnormalities in DCM are nonspecific. Microscopically most myocytes are hypertrophied with enlarged nuclei, but many are attenuated, stretched, and irregular. There is variable interstitial and endocardial fibrosis; scattered scars are also often present, probably marking previous myocyte ischemic necrosis caused by reduced perfusion (due to poor contractile function) and increased demand (due to myocyte hypertrophy). The extent of the changes frequently does not reflect the degree of dysfunction or the patient's prognosis.

Complications:

Biventricular CHF
Bundle branch blocks
Atrial and ventricular arrhythmias
Mural thrombi and systemic embolisation

Prognosis: poor and only 50-60% of patients survive 2 years after presentation.

click image to enlarge

Hypertrophic cardiomyopathy

Epidemiology

Most common cause of sudden death in young individuals
Familial form (autosomal dominant) in young individuals (majority of cases)

Due to mutations in heavy chain of β-myosin and in the troponins

Sporadic form in elderly people

Pathophysiology

Hypertrophy of the myocardium

Disproportionately greater thickening of the interventricular septum than of the free left ventricular wall

Obstruction of blood flow is below the aortic valve

Anterior leaflet of the mitral valve is drawn against the asymmetrically hypertrophied septum as blood exits the left ventricle.

Aberrant myofibers and conduction system in the interventricular septum

Conduction disturbances are responsible for sudden death.

Decreased diastolic filling: Muscle thickening restricts filling.

Gross picture:

- massive myocardial hypertrophy without ventricular dilation

- disproportionate thickening of the ventricular septum relative to the left ventricle free wall

- On longitudinal sectioning, the ventricular cavity loses its usual round-to-ovoid shape and is compressed into a "banana-like" configuration

- an endocardial plaque in the left ventricular outflow tract is often present with thickening of the anterior mitral leaflet. This is correlated to contact between the anterior mitral valve leaflet and the septum during late systole (dynamic obstruction)

Microscopic picture:

- severe myocyte hypertrophy

- myocyte (and myofiber) disarray

- interstitial and replacement fibrosis

Complications and Prognosis:

Heart failure: due to impaired diastolic filling and dynamic outflow tract obstruction (in 25% of cases).
Arrythmias: atrial and ventricular arrhythmias and heart block.
Infective endocarditis of the mitral valve.
Sudden cardiac death: the most common cause of SCD in young adults.

click image to enlarge

Restrictive cardiomyopathy

Etiology

Tropical endomyocardial fibrosis: the most common cause worldwide
Infiltrative diseases

Examples-Pompe's glycogenosis, amyloidosis, hemochromatosis

Endocardial fibroelastosis in a child (thick fibroelastic tissue in the endocardium), sarcoidosis

Pathophysiology

a. Decreased ventricular compliance

b. Usually secondary to infiltrative disease of the myocardium

c. Diastolic dysfunction type of LHF

Gross picture:

- The ventricles are of approximately normal size or slightly enlarged, the cavities are not dilated, and the myocardium is firm.

- Biatrial dilation is commonly observed.

Microscopic picture:

- interstitial fibrosis, varying from minimal and patchy to extensive and diffuse

- disease-specific features can be seen on endomyocardial biopsy (e.g., amyloid, iron overload, sarcoid granulomas).

Prognosis and complications: CHF and Arrhythmias (conduction defects)

Swanton's Cardiology

2009-02-14T19:01:00.004+02:00

This is a really good book for cardiology. I recommend it to all fellows.

Swanton's Cardiology
By R. Howard Swanton, Shrilla Banerjee

Publisher: Wiley-Blackwell
Number Of Pages: 696
Publication Date: 2008-04-11
ISBN-10 / ASIN: 1405178191
ISBN-13 / EAN: 9781405178198

You can download it from here:

Download link

Back to basics: ECG criteria of atrial enlargement

2009-01-14T12:14:00.006+02:00

Righ Atrial Enlargement (RAE):

In lead II: Peaked P wave (A-like appearance)
Normal P-wave duration
Increase in the maximal amplitude of the P wave to >0.20 mV in leads II and aVF, and to >0.10 mV in leads V1 and V2

Left Atrial Enlargement (LAE):

In lead II: gives a notch in the P-wave followed by a second hump (M-like appearance)
Prolonged P-wave duration(>0.12s) and prollongation of the negative terminal portion of P-wave in lead V1
Increase only in the amplitude of the terminal negatively directed portion of the P-wave in lead V1 to >0.10 mV

ECGs of patients with atrial enlargement. Arrows, P-wave changes in atrial enlargement; asterisks, left-atrial enlargement.(click image to enlarge)

Good book: ACLS Review: Pearls of Wisdom

2009-01-14T06:18:00.004+02:00

ACLS Review: Pearls of Wisdom

A very nice book that will help you to master all knowledge needed for ACLS in almost every possible situation. It is in the form of Q&A which makes it more interesting. You can download the 6mb pdf document from either links below.

link 1

link2

New guidelines for appropriateness for coronary revascularization

2009-01-14T06:10:00.003+02:00

These are the recently released guidelines to help in decision making regarding coronary revascularization. They ilustrate 180 possible scenarios and help with appropriate decision in each. you can download the pdf file from here:

http://content.onlinejacc.org/cgi/reprint/j.jacc.2008.10.005v1.pdf.

And do not forget to get your CME credit from medscape here:

http://www.medscape.com/viewarticle/586383

Echocardiography Basics explained by video

2009-01-08T17:14:00.005+02:00

Here is a basic echocardiography course presented by some Indian university as a part of postgraduate diploma on cardiology. The resolution is not so good but acceptable. The videos is a very good start as I think.
part 1

part 2

part 3

part4

The way you think about COPD may change after you read this

2009-01-08T09:28:00.001+02:00

Here is an interesting article about the relation between COPD and cardiovascular risks. I think it may change your way of thinking when you dealing with COPD patients either with associated cardiovascular disease or not.

Impact of Cancers and Cardiovascular Diseases in Chronic Obstructive Pulmonary Disease CME