Dr.S.Venkatesan MD

Archive for 2010

The mystery drug called Ranalozine !

Posted in cardiac drugs, tagged late sodium ion blocker, merlin timi 36, metabolic modulators ion cad, ranalozine, trimetazidine on September 4, 2010| Leave a Comment »

A drug with a peculiar mode of action is recently making waves across the globe (At least some parts of it !) Basically , when the world was looking for an anti anginal drug without much hemodynamic effects Trimetazidine fitted this slot .While it’s popularity soared in Europe and Japan , the Americans thought there was a need for a similar drug but supposedly different mechanism of action . Thus Ranalozine was born.It is a piperazine derivative.

How does Ranalozine act ?

There are three important actions for Ranlozine ( 4th one a real surprise !)

Antianginal
Anti arrhythmic
Possible lusiotropic effect
Anti diabetic*

*It is surprising to note Ranalozine was reducing Hb A1 c . This is incidental or a simple statistical fairy tale we do not know !

Anti anginal

It acts on the late Na ion channel in phase 2 of action potenial .
This facilitates excess Ca to be removed from the cells by the NA/Ca exchanger
Calcium exit improves ischemic myocyte’s metabolic performance as cell injury is prevented .

This makes this drug an effective anti anginal.

The MERLIN TIMI 36 in NSTEMI population became a big dampener against the enthusiasm for this drug.But it did not affect much the sale of the drug !

Antiarrhythmic

A drug , which acts on phase 2 Na channel , it is not at all a surprise to have anti arrhythmic properties .

It can reduce phase 2 reentry like EADS

pro-arrhythmic action

Paradoxically by blocking Na channels it stretches the phase 2 and hence QT interval is prolonged

Lusiotropic action

By preventing the calcium from accumulating from the cytosol it has a theoretical ! lusiotropic action.

It is funny , even theoretical action is enough , for many drugs to enter the standard cardiology literature !

What is major advantage of Ranalozine over other drugs ?

It virtually has no hemodyanmic effects .

Unlike other anti-arrhythmic drugs it acts , only if the late Na channels are abnormally active .

(Which is a case during episodes of ischemia .) This prevents QT interval to prolong in normal persons

In spite of all these meaningful actions and less side effects , FDA approval why cardiologists in the back of the mind think this drug is not based on strong scientific principles , and it could simply represent an industry sponsored placebo ?

I do not know the answer to this question , but I do share the same feeling.

Will it succeed the test of time ?

In this context , I recall a famous statement by my professor “A drug , which has least side effects , is very unlikely to have any desired effect also”

But with world , taking a commercial avatar a success of a drug lies , not in having a desired action but in how many million packs are ultimately sold in the market. It is akin to a bad movie succeeding phenomenally in box office while a good one lying silently unnoticed

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A new “Avatar” in Jugular venous pulse examination

Posted in Cardiology - Clinical, tagged angle of lewis, cvp, jugular venous pressure, jugular venous pulse, sternal angle, two scale vs one scale in jvp, ultrasound and jvp, vertical column of blood on September 3, 2010| 2 Comments »

Looking at the neck veins for hours together has been a favorite pastime of our cardiology ancestors.Thanks to those sharp intellect , that has led us to this height of cardiovascular revolution. Measuring JV pressure by itself was considered a big science. Putting a patient in 45 degrees , marking the sternal angle, identify the oscillating venous column, measuring the vertical distance etc . . .

Now in 2010 , with bedside hand-held echo one can rapidly rule out an elevated central venous pressure by imaging the jugular vein directly . Here is an article from American heart journal

http://www.ncbi.nlm.nih.gov/pubmed/20211304

Simon MA, Kliner DE, Girod JP, et al. Detection of elevated right atrial pressure
using a simple bedside ultrasound measure. Am Heart J 2010; 159:421–427.

Soon , your mobile will double up as ultra-portable echocardiogram

Read this related article in this blog .

Coronary care in your pocket

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What are the clinical signs of obstruction in HOCM ?

Posted in Cardiology - Clinical, cardiology -congenital heart disease, Cardiology -unresolved questions, Uncategorized, tagged hcm, hocm, hypertrophic obstructive cardiomyopathy on September 2, 2010| Leave a Comment »

Hypertrophic cardiomyopathy (HCM) manifests with or without obstruction. Obstructive HCM , (ie HOCM) is more often symptomatic .However , the risk of arrhythmias, sudden death, and some degree of diastolic dysfunction are common in both.

ECG, clinical examination are generally not sensitive to identify obstruction in HCM .Echocardiogram is the easiest way to identify the obstruction (gradients> 3o mmhg across LVOT are considered significant ).LV angiogram ,MRI, CT scans are rarely necessary today.

However , the following clinical clues will help us to suspect significant obstruction in HCM

History

Class 2 or 3 dyspnea.
Exertional syncope
Exertional angina

Pulse

Pulsus bisferiens (Two peaks in systole )

LV apex

Sustained , double apical impulse often indicate obstruction.
Presence of Mitral regurgitation ( 20% can have MR without obstruction due to intrinsic abnormalities of mitral valve )

* It should be realised , valsalva induced MR /LVOTO may occur in many of the non obstructive HCM.

What happens to clinical signs of obstruction with medical therapy(Beta blockers etc)

One would expect these signs to regress or disappear, but it rarely happens. The pulse , the murmur show little change . This implies , the main mechanism of beneficial effect could be in heart rate reduction , and improvement in the diastolic properties of left ventricle.

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Why ACE inhibitors are contraindicated in bilateral renal artery stenosis ?

Posted in Cardiology hypertension, Infrequently asked questions in cardiology (iFAQs), Uncategorized, tagged ace inhibitor, acute reanl failure, aniotensin 2, bilateral renal artery stenosis, bowman's capsule, chronic renal failure, ckd, efferent arteriolar tone with acei, efferent arteriole and ace, gfr, hyper filtration, intra glomerular hypertension, renal toxicity of acei, reno protective effects of acei, serum creatinine eelvation with ace inhibitor on September 1, 2010| 5 Comments »

It is traditionally believed , renal blood flow is critically determined by the luminal diameter of renal artery.But in reality there are more important factors other than renal arterial diameter that determine the glomerular blood flow. As in any vascular bed, it is the arterioles that determine the resistance and hence the flow . These arterioles form the critical resistance points and acts as check valves in this “vascular highway” flowing across the renal terrain !

Unlike other micro-circulations , the kidney has a special job to do , ie filtering the toxic molecules. Hence, for the blood entering the kidneys , even nourishing the kidney seems , a less important function ! The nephrons of the kidneys are probably the most “high – tech” cells in human body (Of course ,next only to brain cells ) .The vascular tuft of glomerulus located within the bowman’s capsule is perfused by afferent arteriole and drained by efferent arteriole .

The entry of blood into glomerulus is regulated both by afferent and efferent arteriolar tone .These two micro-circulaoty units are under the sensitive control of both neural and humoral signals. Glomerular circulation is meticulously regulated by renal juxta glomerular apparatus.It modulates the glomerular blood flow by secreting renin which acts through Anigiotensin 2 on the efferent arteriole .

The tone of the efferent arteriole is thought to be the single important factor in this servo control mechanism.

What happens in bilateral renal arterial stenosis ?

When there is bilateral renal arterial stenosis the effective renal blood flow is not significantly reduced , but maintained at the cost of increasing the efferent arteriolar constrictor tone. It is like a check valve at the exit point of a dam , which is partially closed to maintain the adequate pressure head (Here , intra-glomerular pressure head )

What happens when ACEI are introduced ?

Once ACE inhibitor is administered , the efferent arteriolar tone is removed , this triggers the intra glomerular pressure to drop suddenly and filtration pressure reduces .

Note: ACEI does not reduce the renal blood flow directly but the glomerular perfusion pressure drops hence precipitating acute renal function deterioration.

What is your comment about the reno-protective effects of ACEI ?

The medical science’s most crucial moments occur , when we confront two diagonally opposite views are debated and both suggest , there is definite benefit for the patient ! Cardiologists and nephrologists were always made to believe , ACEI are unfriendly to kidneys . But ,we now have evidence , ACEI is not an untouchable molecule in renal dysfunction.

This is based on the observations made , over the years that excess Angiotensin 2 is ultimately a liability for the kidneys !

Looking at a long term perspective , AT 2 increases the intra -glomerular hypertension and ACEI inhibitors reduce it.This pr0tects the nephrons from hyper-filtration mode , that accelerates the glomerular injury . So , the current thinking is ACEI has a definite role in arresting the progress of renal cell injury .

This is akin to beta blocker story in CHF which was initially contraindicated in CHF later became a definite indication

The only issue for ACEI is , it should not be continued if an ARF like picture sets in .(Acute deterioration ). Otherwise , in CRF at any basal level of serum creatinine , ACEI can be continued . Some think even an increase by few mg of creatinine can be allowed .

So the following can be a working guideline *

ACEI can be started or continued at any level of creatinine in stable CKD with or without dialysis

But ,ACEIs need to be stopped in all of the following

Acute renal failures
Acute on chronic renal failure
Accelerated elevation of creatinine (As in bilateral renal artery stenosis)

How much elevation of creatinine is allowed in CKD with ACEI ?

This is not answered yet .

*Caution : The above conclusions on ACEI and creatinine was derived by me , based on with personal discussions with my Nephrology colleagues. It may be subjected to correction.

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When will you suspect reno vascular hypertension ?

Posted in Cardiology hypertension, Infrequently asked questions in cardiology (iFAQs), Tutorial in clinical cardiology, Uncategorized, tagged astral reanl artery bruit, renal artery stenosis, renal hypertension, renal parenchymal hypertension, reno vascualr hypertension on September 1, 2010| Leave a Comment »

The much fancied criteria “suspect secondary HT” if the onset of hypertension is before 30 years later than 55 years ,may be useful .But a caution about this criteria : It does not mean you should not hesitate to diagnose renal HT between 30 -55 years. The real onset may be < 30years , but the patient may report to the physician late in his /her 40 or 50s !

Diastolic blood pressure > 120
Sudden acceleration blood pressure
Blood pressure which is resistant to control with three or 4 drugs ,that shall typically include a diuretic.
An episode of left ventricular failure (Often referred to as called flash pulmonary edema)
Presence of Hypertensive retinopathy
Para umbilical bruit
HT associated with significant CAD
Marked LVH in echocardiography
Finally , most importantly , worsening of renal function with ACE inhibitor is a strong clue the kidney is under perfused and the renal circulation is dependent on elevated angiotenisn 2 (Which ,if blocked worsens the GFR ).This implies every physician should take a baseline serum creatinine and urea before starting them on ACEI.(Which is rarely followed , as far as my country is concerned !)

Is there any simple way to differentiate reno vascular from renal parenchymal HT ?

It is very difficult to differentiate between these two clinically. It makes things more difficult , as combination of both occurs. Prolonged renal ischemia can result in parenchymal damage as well.

The simplest way is to do a rapid ultrasound imaging to assess kidney size and texture (Loss of cortical-medullary differentiation indicating early renal contraction phase ).Of course , our nephrology colleagues are always there to help you out .

* It need to be remembered the functional renal HT -Renal tubular acidosis, Adrenal HT (Conn’s /chromo-pheocytomas has to be ruled out , as these entities also occur in the same age group ).The combination of hypokalemia and mild alkalosis is a good clue to rule out many of these defects.

* The CT scan image used in the above illustration courtesy

http://www.ajronline.org/cgi/content-nw/full/189/3/528/FIG21

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It is heard loud and clear ! Death knell for routine stenting for renal artery stenosis !

Posted in Cardiology -Interventional -PCI, Cardiology hypertension, Uncategorized, tagged acc aha, astral study, consensus statement on reanl angioplasty, fibromuscualr dysplasia, medcial vs stenting in ras, reanl angioplasty, renal artery stenting on August 31, 2010| Leave a Comment »

For medical science to defy logic , is a not a great new discovery . “Diabetes is a major risk factor for heart disease but controlling diabetes may not remove this risk factor” Similarly severe mulitvessel CAD occurs without any symptoms and compromise on LV function . It is a natural human instinct to open of any thing that is obstructing on their path . The same logic applies in physicians when we encounter blocks in the vascular highways .

For a moment compare it with an express way .

We realise many roads have a reserve capacity . Even if the road is half blocked , traffic congestion rarely happens as the original road’s width is sufficiently large for the projected traffic . Some other roads have emergency service lanes (Collaterals) that can take care the flow of traffic.

Another question to ask is , Where does the road lead to ? and why we are traveling ?

If it leads to a “dead sea” or a “bottom less cliff’ there is no purpose to travel further . Similarly , when you find a destructed kidney with little nephron mass( or dead myocardium ) there is absolutely no purpose in opening the block . (Some may believe the act of opening block , by itself is a success / sorry- story !)

This is what happened in the lase decade . Interventional radiologists , vascularologists , cardiologists started opening renal artery obstructions , at their whims and fancies, in many elderly and middle-aged population .To their surprise (This surprise is due to ignorance ) they found no worthwhile benefit either in the BP reduction or worsening renal function .

Now comes the evidence in 2009 as ASTRAL trial from UK . ( As usual the evidence came late after , few lakhs of kidneys been injured !*

* Renal interventions are notorious for many complications , which is often not reported . Read this article to know it better.

http://www.nejm.org/doi/pdf/10.1056/NEJMoa0905368

Final message

Common sense can work great wonders than the much hyped RCTs . (Except ASTRAL of course !) In this era of scarcity of such sense we can expect another study soon , to nullify ASTRAL and give us further license to pursuit the good old human instinct ! Already silent noises are made in interventional corridors questioning the outcome of ASTRAL.

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How common it is , for an “Acute STEMI” to present with stable ventricular tachycardia ?

Posted in cardiology -Therapeutics, Cardiology -unresolved questions, cardiology- coronary care, Cardiology-Arrhythmias, Uncategorized, tagged ischemic ventricualr tachycardia, ischemic vt, primary ventricualr fibrillation, primary ventricular tachycardia, primary vf, scar induced vt, stable vt, stemi presenting as vt, vt in stemi on August 31, 2010| 2 Comments »

Acute MI and ventricular tachycardia are closely related entities.In fact , the earliest response to ischemia could be a VT .But what is peculiar about this VT is, it almost always degenerates into VF within a minute or so.(Unlike idiopathic VTs /RVOT/LVOT VTs)

This arrhythmia in every sense can be called as “primary VT“ which is the cause for “primary VF”

It is strongly believed VF cannot occur without a brief episode of VT preceding it .Logic would also suggest the ischemic myocardium can not suddenly become chaotic “with the first beat “. There is little documentation available to unprove this presumption.

In spite of this intimate relationship between VT and STEMI , it is very rare for a STEMI patient to enter ER with a sustained stable ventricular tachycardia . While many VTs are known for it is hemodyanmic stability and immunity against degeneration into VF , it is extremely rare for VT to remain as VT in acute STEMI.

*Note : NSVT can be common in hospitalised patient in the coronary care unit . In our experience a sustained VT in STEMI will enter the VF mode within 60 seconds .If not , it is a highly unusual phenomenon .

“But surprise is the other name of medicine ”

Here is case report, a patient walked into coronary care unit with sustained( relatively stable) VT with LBBB morphology .We thought it was a non- ischemic VT (cardiomyopathy , RVOT etc) .As we were examining him, he became unstable and was shocked 50 J biphasic .To our surprise a classical STEMI was unmasked and he was immediately thrombolysed.

* It is possible , the patient had suffered a old MI which got infarcted again and the VT was scar mediated .

But it is still uncommon for it not to degenerate into VF with fresh STEMI

Final message

Nearly all episodes of ventricular tachycardia , that occur in the early minutes/ hours of STEMI would degenerate into VF.This includes VTs that occur within the CCU . Most of the times , the CCU physicians and staffs revert this VT promptly and deny the ventricles from performing the dance of death !

It is extremely rare for an acute ischemic VT associated with STEMI to walk in to the hospital, which our patient did !

Further reading and unanswered questions

What determines a VT to degenerate into VF ?
Why macro-reentrant , scar dependent VTs often are well tolerated ? ( In spite of LV dysfunction !)

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Left atrial pressure volume loop

Posted in echocardiography, Infrequently asked questions in cardiology (iFAQs), Uncategorized, tagged atrial compliance, atrial distensibility, atrial stiffness, left atrial fucntion, pressure volume loop of left atrium on August 28, 2010| Leave a Comment »

We have read extensively about LV pressure volume loops . What about Left atrial pressure volume relationship ?

This could be vitally important to understand left atrial failure . While, it is often taught that , LA comes to the rescue of left ventricle at time of stress , we rarely talk about left atrial failure !

Where will the LA look for help when it is stressed ?

Pulmonary veins ? , No , the LA simply succumb and patient deteriorates.The only way it can react is by a panic response and starts fibrillating !. This is what happens in many cases of dilated cardiomyopathy and late stages of aortic valve disease . This AF is very poorly tolerated . ( Of course , we do not understand fully , why AF is relatively well tolerated in severe mitral stenosis , inspite of very high LA pressures Often >40mmHg?)

The importance of left atrium as a mechanical chamber is well recognised .It is supposed to empty the blood it receives from pulmonary veins within a narrow pressure zone of 8-12mmhg within a fraction of a second. Even a slight increase in LA pressure may result in pulmonary venous regurgitation and the incoming venous tides are reversed(“a” reversal in pulmonary vein echo ) that results in the so called pulmonary congestion /Pulmonary venous hypertension.

If only god has created additional pulmonary venous valves** at it’s entry , LA can perhaps a relax a little bit . But it is not the case . So, LA function becomes as vital as LV.

(**Can we create pulmonary venous check valves ? . . . will it be an answer for preventing recurrent LVF in cardiomyopathies etc)

Here is an article from European heart journal , which gives great insight into Left atrial function.

The one that has fascinated me is the LA pressure volume loop.

The two pressure waves in left atrium reflect distinct properties . “v” wave is a volume dependent wave and “a” wave a pressure generated wave . Surprisingly the volume dependent wave generates more pressure than the atrial contraction wave.(Note in LA v > a while in RA a>v)

http://eurheartj.oxfordjournals.org/content/22/1/22.full.pdf

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Ascites precox

Posted in Uncategorized, tagged ascites precox, constrictive pericarditis, pericardial reflection over ivc on August 28, 2010| Leave a Comment »

Fluid retention is a classical sign of cardiac failure . (Elevated JVP, hepatomegaly , edema legs ) The mechanism of fluid retention are many .But, traditionally we have given importance to venous back pressure (Hydrostatic pressure) . Equally important (if not more !) is the renal sodium and fluid conservation in response to reduced effective renal blood flow.

How common is ascites in cardiac failure ?

While we see hydrothorax little more frequently it is rare to get ascites in cardiac failure .However ascites often manifests late in the pre terminal phase of cardiac failure *. This is due to congestive hepatomegaly, secondary hyperaldosteronism and renal dysfunction .

When does ascites come early before edema of extremities in cardiac failure ?

It is classically reported in constrictive pericarditis. The reason why ascites precedes edema legs is long been speculative . Now we have evidence , the pericardial pathology , has a direct effect on the hepatic venous morphology. There can be a selective , partial constrictor effect on at least one of the hepatic vein as it enters the right atrium .In fact , the entry point of hepatic vein is delicately close to IVC/RA junction.

*It should be remembered in the current era we are expected to diagnose cardiac failure even before the onset of edema !

Anatomical constriction has a mechanical effect on the hepatic venous drainage and subsequently alters the hepatic function . Segmental hepatic dysfunction is thought to ooze out the ascitic fluid from the surface of liver .Ultimately severe raise of hepatic venous pressure results in congestive hepatomegaly and could result in now obsolete , cardiac cirrhosis.

Other mechanisms of ascites in constrictive pericarditis , include

Hypoprotenimia
Common infection of peritoneum and pericardium( like tueberculosis)

Is ascites precox an exclusive feature of constrictive pericarditis ?

Not necessarily so . Even though , it was first described in this condition ,clinical experience suggest, any congestive cardiac failure with predominate right sided pathology like organic tricuspid valve stenosis or regurgitation, right ventricular endomyocardial fibrosis , all can result in significant ascites which may precede edema legs.

What is effect of of severe TR on hepatic venous hydrodynamics ?

TR like MR can be eccentric and some times hits upon the hepatic veins directly

and result in disproportionate elevation of hepatic venaous presure than even IVC pressure

which may contribute to early ascites in organic tricuspid valve disease.

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