Archive for the ‘cardiac drugs’ Category

This cartoon succinctly  depict all the options we have in our fight against end stage heart failure .We know , a failing heart is often compared to a sick , aged and tired horse.

cardiac failure cartoon tired horse whicpping lionel opie book

Image courtesy Heart Physiology: From Cell to Circulation :Lionel H. Opie Lippincott Williams & Wilkins, 2004


1.Don’t whip the horse (Except in emergency)

  • Avoid all Inotropics ( Doubutamine and Milrinone were shown to improve quality of life marginally but  with dramatic reduction in quantity of life ! However , the same thing does not apply for Digoxin as it is the  the only Inotropic with a soothing para-sympathetic comfort  !
  • Please be reminded, CRT wires could act as  “multiple whip equivalents” right inside the heart , especially in advanced class 3 or just recovered class 4 patients. Beware!

2.Unload the horse



3.Slow the horse

  • Never exert too much (Not more than 70% of capacity)
  • Beta blockers
  • Ivabradine (Slow the sinus node and expect a reduction in MVO2 )

4.Change the horse

  • Heart transplant may be the best solution

5.Switch to an Artificial Horse(Tractor )

  • ie  LV assist device

6.Finally try to heal the horse (Still largely in research labs!)

  • Genetic engineering
  • Tissue repairing
  • Stem cells
  • Holistic and spiritual healing etc (Has really  worked in few )

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This was question thrown at me ,  in one of the  patient -physician meet .

“I am a 58 year old business man . I am taking tab Atenolol 50mg for over  6  years .I am comfortable with that .My  BP hovers around 130 /80 mmhg .My heart rate is 64/mt . I have recently  moved to a popular city in south India  . Now , my cardiologist thinks Tablet Atenolol  for hypertension is useless  . . . what do you say sir ?

My answer went on like this  . . . causing much  displeasure  to my  colleagues !

Atenolol  is a  wonder drug for management of both hypertension and angina for more than 2 decades .  It is  still useful in majority of patients with HT .

The reason for  current generation of cardiac physicians   shunning  away  from this drug  is  largely  for  non academic reasons . A drug which is  in market for more than  a decade ,  generally becomes a generic one. Generic drugs are  like  orphan drugs !   and patients  who consume generics are inferior ones .This is how market economics want us to think .

Physicians are sincere followers of  science and science is not sacred ,  often times  . . .  it is the creation  of   corporate gimmicks .

Few small  studies ,  one major publication  , few guideline   from  influential    scientific bodies  , cocktail of   seminars  , symposiums   all that  is required to disseminate  a concept !

The second major reason is every physician wants to behave in unique way . He fears loosing  his prestige and  charm  if  he  continues the same drug prescribed by another physician  . Many patients also do not like to continue the same drug for long time  !

And now a few words for the cardiac scientists !

*The concept of central aortic pressure and beta blocker’s lack of control over it are all concocted .Beta blocker is most powerful agent to reduce the shearing stress in the walls of aorta . We know that and we believe in that and we prescribe it for aortic dissection to attenuate the intimal tear . Can it do this  . . . without lowering central aortic pressure ? Think for a moment !

Atenol and Metoprolol : The curious  companions .

Both being   closely related beta blockers ,  what makes  Atenolol  to be frowned  upon   and  still   Metoprolol  is  alive and kicking  !

 My final answer to your question !

Atenolol is still useful in the management  of HT. If your BP is well controlled ,  and you have no side effects,  there is absolutely no need to change  the drug   . . .  if  you are  insisted  , you may consider  changing  your doctor   . . . . . .  rather !

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What happens to  bleeding time  with   antiplatlet drugs ?

  1. Does not have any effect
  2. Prolongs  it marginally  .(This can not be detected accurately by the conventional  Ivy  bleeding time)
  3. BT is  significantly prolonged at therapeutic doses .Bleeding time is useful to monitor efficacy of these drugs.
  4. Prolongs only with loading dose hence it has no clinical  utility .

Answer :

I have been struggling to find an answer in the literature .  Response 2 seems to be  correct .

Back to basics

We are taught reverently  in the first clinical year  at  medical schools ,   platelets are primarily responsible for   stopping  the capillary bleeding . Clot formation follows later . The coagulation cascade occurs over the platelet plug with number of mediators  from platelet  taking part in the clotting process.

If  anti-platelet drugs  functionally  paralyse the platelets ,  it  must  prolong the bleeding time . If that is so ,  why  we  are simply not bothered about measuring bleeding time  to assess the efficacy of anti-platelet drugs ?

Surgeons tell us every other  day about the  ooze in a patients pretreated with aspirin. In fact there is very good evidence for this . Following data is taken from  the journal  “Blood” in 1969 .

There are few  important reasons why bleeding time  is  not in vogue to monitor anti-platelet efficacy

  • A marginal elevation (  say  . . .  from 6 minutes to  8 minutes  ) may not convey any  meaning (Is it really  so ?)
  • The method of bleeding time measuring is  primitive one ( Ivy ) and it is time-consuming (Since the normal bleeding time can be up to 3-9 minutes   ,it is too long period for the  modern day cardiologist )
  • A prick  has  to be made  and the patient  may  feel awkward.(While he can very  well tolerate  the nicks in radials and femorals !)
  • Simple BT  costs nothing and can be readily done in bed side , while digital platelet  reactivity testing adds  spice ! It  would be humiliating  for   a  cardiologist  (who lands to the cath lab in  a Audi saloon )  to order for simple bleeding time

So what does the  newer platelet assay tools do ?

Ironically  , the currently available   sophisticated point of care platelet function test is   grossly error prone .Currently they are not recommended  for routine use . So what is the big deal ?  Modern  physicians  has no right to ridicule the  age-old tests ! . In fact  should try to  give a new lease of life  to  the conventional  BT .

I personally feel  there could be a role  for  conventional BT in    an  occasional   patient   after  complex angioplasties . Confirming the  adequacy  of  anti platelet  drug is critical   .  A simple   one time  monitoring of  bleeding time  24-48 hours  after  a PCI  with full dose of anti-platelet  drugs  should help us track and monitor the efficacy  these drugs .  My  guess is  it can be kept  at upper border of normal or slightly above it . If we know the basal  bleeding time it will be added advantage as one can prolong  it  more objectively.

We plan to undertake a simple study of effect of loading dose of clopidogrel  on the  bleeding time . The results will be reported .

Final message.

Ignoring age-old basic medical concepts is  a  serious  threat  facing  the  current   medical professionals . Can we afford to  ignore a  grossly elevated ESR   in a patient with fever , since it is cheap and primitive investigation . Similarly a   low bleeding time   in a patient with  dual anti-platelet therapy   and a drug eluting stent   would  convey a  serious message ,  (All is not well   In  terms of adequacy of platelet inhibition.   ! )


  1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995097/pdf/nhj1529900.pdf (Point of care instant platelet function testing)
  2. http://bloodjournal.hematologylibrary.org/content/34/2/204.full.pdf
  3. http://en.wikipedia.org/wiki/Bleeding_time

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Magnesium   is a powerful anti-arrhythmic drug . It has a well  established role in controlling VT when administered  Intravenously   especially in polymorphic VT .

Mechanism of action

  • It acts at the cell membrane.
  • It has a unique action of blocking calcium channels  that reduces the number of oscillations of  both  early and late  after potentials

Link for more  on mechanism  of action


How often cardiologists administer oral magnesium for long-term control of VT ?

As for as I know ,  no one uses it ! but dietary  supplements are used for general well  being .

Why ? Is it because

  1. Magnesium does not get absorbed in the gut
  2. Magnesium levels are un- predictable in plasma if administered orally

Answer : No one has really tried  it as a  chronic therapy in VT  yet  !

Final Message

Tablet Magnesium can give a tough fight to Amiodarone and Flecanaide in refractory VT at a fraction of the cost !

Who has the audacity  to  compare Magnesium  with Amiodarone head on ?


Magnesium as health supplement . 

Magnesium is available  in tablet form as  Malate , Stearate, Taurate and Aspartate  along with calcium and Zinc etc .

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International Astronomical Union  in the year 2006  removed Pluto from the solar system for a simple reason ,  the so-called Pluto never revolved around  Sun , hence it ceased to be a planet of the solar system , it was more of an asteroid !

So, an astronomical fact engraved in our brains for so long  became a fairy tale. It is very hard  to erase  a  myth however solid the new evidence are against it.

The concept of HDL as good cholesterol has been etched deep in physician as well as our  patients.

Now comes the shocker from Lancet

How are we so sure ,  about these  Invisible spheres of  lipids that  move  around  our “Bio-system” in a presumed fashion .  .  .  even huge visible planets  fool us easily !

The Link to lancet study

It is  a wonderfully done study where  thousands of patients  who exhibited  genetically high HDL levels , never showed any advantage in terms of CAD prevention.  A stunning blow to a belief.

Incidentally ,  few years back  the failure of  drug Torcetrapib proved the same point  .  (The drug which elevates  HDL  proved useless in preventing CAD  ) but the  medical world failed to interpret it properly.

I am sure, still sections of physician  community would continue to believe HDL is great molecule for CAD protection !

Science is  often what we presume . . . but the fact usually turns out to be some thing  else !  but the journey towards truth  must continue !

                      When  a  million tonne  Pluto  suddenly disappear from Solar system . . . it is not a  big deal for  a  “miniscule medical myth”   to get shattered !

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Amiodarone acts  by

  1. Correcting the  rhythm  to sinus .
  2. Controls  ventricular rate  alone
  3. Does both ?

Answer is 3

How can it correct the rhythm alone ?  If  the rhythm is corrected ,  rate will automatically be controlled,  unless Amiodarone converts AF into Sinus tachycardia  which is very unlikely !

Of course  Amidarone  is not a  magic drug .The success rate of  Amiodarone  restoring  sinus rhythm is far . . . far less . . . than our expectations ! . It fails to  convert to sinus rhythm in a significant chunk *. Interestingly ,   it may still  control the  ventricular response  by its beta blocking action .

*Our estimate is , the failure rate Amiodarone  is  between  30-40%  or even higher ,  as   bulk of AF we witness   is due to Rheumatic heart disease.

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The mechanism of pedal edema in Amlodipine

Note : I lost track , the source of this Image .I thank with courtesy whoever has created this Image .

It is primarily a  local phenomenon . The calcium channels  are primarily  arteriolar dilators . Since the  venules  lack much muscle they  are not much affected by the Amlodipine   .  This  facilitates flooding of  venules and leaks into the peri venular interstitial space. It may be apt to call Amlodipine induced edema  as a form of   local venous edema .

This results in near permanent  collection of fluid  especially  near  the ankle . Systemic fluid retention has no major role . However few patients may  show an  augmented   RASS  response due to sudden arteriolar dilatation  .  In these patients   addition of ACEI or ARB may help relieve  edema legs .The Amlodipine  induced edema is  dose  and  time dependent .(Cumulative)  . It is mostly benign in nature ,  rarely warrants withdrawal of the drug.  The edema can  occasionally be generalised   and weight  gain is  possible .

Other factors that increase the chance of edema is age , women  , obesity. They have loose  interstitial  tissues.Many especailly women complain tingling feeling in the edematous zone.

The calcium blocker induced edema is  an  exclusive feature of dihydrpyridine group  .(For some reason  , Verapamil and Diltiazem do not  share  this side effect  as  theya balanced Arteriolar and venous dilator . )

Can we use diuretics to treat Amlodipine induced edema legs ?

Hydrochorthiazide  is rarely useful as the primary problem is not in the renal  retention.

How to  treat Amlodipine induced edema ?

Unfortunately the popular combination with diuretics do not work . Angiotensin  inhibitors which has some veno dilatation is shown to reduce this edema  . ( COACH study . Olmesartan / Telmisartan combination  is an option ) .It defies logic ,  to  add  another anti HT drug for the sole  purpose of reducing  the side effect of the initial  anti HT drug . Ideally if  your patient is not tolerating  Amlodipine due to edema ,  switch to  an another group of  anti HT drugs.



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Aspirin under attack  . . . not by  Gastro-enterologists  this time ,  but by cardiologists themself  !

Aspirin , after all may not be safe ,  as a primary prevention drug against CAD . It  seems ,  it considerably increases  the risk of   bleeding . The  new meta analysis just published in Archives of internal medicine  says so !

Be cautious it concludes  !  Since the  track record of evidence  based  medical science  ( and its reproducibility  )   looks   pathetic  in recent times  ,  we may expect another  stunning  study  very soon , with an exactly opposite conclusion  !

After thought

So , we have a  “vacancy  in  the top slot”  for primary prevention of CAD . Mind you ,  makers of  Prasugrel and  Ticagrelor  are already  fastening their seat belts !

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Uric acid is a  metabolite of purine metabolism.Purine is dynamically present in  every  active multiplying cell .Uric acid is formed when Xanthine oxidase  acts on   Xanthine and hypoxanthine  which are products of purine . The estimation of serum uric acid level can give us a rough estimate of cell metabolism and turn over. We need to  understand there is a dietary source for purines as well.

UA is mainly  excreted in urine . Normal levels of UA is   3-6mg in women and can be 1 mg higher  in men

Biological actions of uric acid

UA is a physiological molecule . It is more of an byproduct  and  devoid of any unique  action. Hence , most physicians still   believe it to be an unwanted  dangerous toxic molecule. What we fail to realise is ,  uric acid is a strong natural reducing agent .Hence it acts as an antioxidant .(Comparable to Ascorbic acid Vit C !)

Some believe excess uric acid is  a natural metabolic weapon against cellular degeneration . In fact , hypo- urecemia has a well known  association with multiple sclerosis and augmenting UA  is known to improve multiple sclerosis.

However, the problem with this  physiological molecule  is ,  we do not know yet,  when the  levels become pathological .We know uric acid in excess can lead to  urate stones  in kidney and Gout in joint . Does these crystals have any effect on coronary and cerebral circulation ?

Is uric acid a marker of inflammation and cell turn over ?

Yes it is.  What ESR  means to  inflammation , uric acid means for cell turnover . Since Inflammation induces white cell turnover  uric acid  level  becomes   a marker of inflammation as well .

Uric acid in  excess  is a  marker of vascular  damage as  atherosclerosis  is an inflammatory process  , especially  with  pulmonary endothelial damage. So , in patients  with primary pulmonary  vascular diseases  like PPH , uric acid levels   may indicate  the progression or regression of PAH.

Some studies have correlated right atrial pressure with uric acid levels.

Uric acid and hypoxic states

Uric acid formation is more in hypoxic states as hypoxia depletes ATP and adenine metabolism is promoted and more inosine and  Xanthines  are produced . Uric acid can be a simple  marker  of increased oxidation stress of human biological system.

No surprise  to note   pulmonary hypertension  an important hypoxic state  increase uric acid levels .

Why uric acid is rarely considered as a useful diagnostic marker in cardiology  ?

  • The major  reason is it is an old molecule and has  lost its  flavor .
  • The name is not exotic (Like BNP, Di dimer etc)
  • Finally it is  a  cheap investigation and hence  lacks the required glamor.

Technical limitations

  • Uric acid levels are non specific (Like any other  modern  molecules  Tropinin , CRP etc! ) No one  would like  to compare uric acid vs hs CRP one to one as a marker of inflammation in vascular  disease.
  • UA  levels depend on kidney function .
  • Dietary influence can be significant (Especially meat, Liver Beans, Cauliflower etc)

Knowing the  basal level of uric acid  in a given patient ,   help us  monitor the net cell turnover during medical   management of chronic illness.

UA’s Clinical utility in cardiology practice

Importance of UA in PAH   is well recognised now  . Most studies on PAH  use it as a marker  or even  to define a therapeutic endpoint  But , please remember  elevated uric acid is a  simple  index of elevated  cell turnover and oxidative stress and it mainly represent  the effect of  pathology rather than a pathology itself.

So , attempting to reduce uric acid levels   with drugs like  Allopurinol may not  improve the  vascular function as one would wish ! The only indication for  reducing uric acid level   is  when the levels   become  too much and it starts depositing   in body.

Final message

Uric acid is a useful bio marker for  vascular function. It can indicate  the  quantum of  inflammatory , metabolic  and cell turnover of any progressive vascular  disease. With serial measurements  it definitely helps us in monitoring   cardiovascular disease  especially pulmonary hypertension  as  lung tissue is major source of this molecule . Now , uric acid  is used  for prognosticating  cardiac failure also.









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Off label prescription 

  1. Is a great scientific concept
  2. Is a deceit camouflaged  with a pseudo scientific fabric.
  3. Can be encouraged in very selective patient  population and diseases by experienced  cardiologists , as  it may be really useful when no other options are available.
  4. Is diagonally opposite  to evidence based medicine , should be banned in toto !


4 is the correct answer .occasionally 3 can be true

Some of the examples of off label indication

  • Statins for Aortic stenosis
  • VSD device for RSOV closure
  • Ivabradine for cardiac failure

By the way how does an off label become on label?

It is not the ” God ” who  gives the label to them

There are few “Demi Gods” sitting aside  in the regulatory corridors of  New york and  Geneva who decide the fate of these drugs and devices . Ultimately the integrity of these organizations that will either protect or injure our patients !

Final message

Medical science grows my mistakes  . . . hence  we should be encouraged to do more of that  . . . so that we can grow !

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