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Posts Tagged ‘bmj’

                                                    Drugs are poisons , whenever it is administered without valid purpose. it can enter human body  in many ways (Oral, intravenous, percutaneous etc ) And now we have another route namely intracoronary !

                                                   In quest for prevention of restenosis, many of the anti cancer drugs are now delivered directly inside the coronary arteries .These drugs are secreted  like a sustained release  tablet from the drug coated stents.These drugs are expected to prevent restenosis within the stented segment.But, after years of  intense debate and research  , we realised that ,  drugs  eluted from the stent  could damage the distal coronary vascular bed and coronary microcirculation.( And thus came the epidemic of acute stent thrombosis ! )

                                                The tender and sensitive coronary microvasculature  is constantly exposed to  these  powerful anticancer and immmunosuppresive  drugs .It is a great surprise , no body thought of  this dangerous drug -coronary artery interaction ! It required the genius of Renu virmani and others to point out this.

But still , the cardiology community by and large , fails to consider  this an important issue.This is proven by the fact, usage of DES is  still increasing  and used mainly as an off label indication.

Read this land mark article from circulation

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http://circ.ahajournals.org/cgi/content/full/115/8/1051?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&author1=renu+virmani&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&fdate=1/1/2007&tdate=12/31/2007&resourcetype=HWCIT

 

Questions that need to be answered

  • What is the long term effects of drugging a coronary artery ?
  • Is no reflow or slow flow  more common after DES , because of the adverse drug reaction in the distal vascular bed ?
  • If a patient  with  DES  undergoes a CABG later what  would be  the impact of the  drug on the graft ? Will the functional vasodilatation   affected ?

Final message

                                  A drug , to get a legal clearance it has to undergo  hundreds of rigorous tests . Finally it is cleared for that  specific indication for which it is tested  .Just because a drug is cleared for one purpose ( Paclitaxel for malignancy ) it does not mean it is safe to use for any other  purpose for which it is deemed to be useful . Exactly the  opposite is happening   in the  the field of interventional cardiology . No body wondered to think what would be the effect of these drugs on the normal coronary endothelial cells and vasculature.Is it not a crime ,  without analysing this particular issue  , dozens of drug eluting stents have been released in the market . And now,  sounds of crying  foul is heard world wide !

Let us thank  , the so called negative forces in cardiology  for making this an  issue . In science ,  the watch dogs should bark  at  times of danger not wag the tail !

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Drug eluting stents : A slap on the face of Evidence based cardiology . . .

Click the BMJ link or read below

 

venkat-bmj

It is often said science is sacred and unfortunately we forget ,  science is not a heavenly creation and it is the creation of scientist of varying grades of integrity fueled by the vested interest of medical industry . It has been a almost a daily affair , some of the devices and drugs are recalled or found to be unsafe on patients.

Now the big cat has come out .The Drug eluting stent has fallen from Hero to Zero in a short span of 5 years. It was projected to have zero percent restenosis in 2002 . And now we realize it is Zero percent truth.

What has started as anecdotal reports of late stent thrombosis has indeed become an epidemic in all DES patients. The five studies that has been published in the NEJM this month (March 2007) has convincingly proved how unsafe these stents are in most of the coronary population .

Millions of patients in whom this stent was implanted will carry an impending stent thrombosis and possibly an SCD . Who is to take care of them ?

The DES story is a clear cut case of getting premature approval for a dangerous form of treatment inside human coronary arteries.

It is amazing how the scientist’s eyes are shut by the illusion of knowledge and lure of wealth. How foolish they were to think drug which was administered via the stent will selectively prevent vascularisation and leave the normal endothelium intact . Now they realized , one should not suppress the endothelial growth around the stent and got the fundamental point wrong. Which was the key reason for the astonishing episodes of late stent thrombosis. When we play with biology of nature we have to be little more careful .God has created man and his heart for over a million years . One can not alter it by a 6 month follow up study of DES .

When ICDs were exposed last year , of similar disastrous outcome they were recalled and explanted . How are we going to unstent the millions of coronary arteries ?

Somewhere along the line the medical professionals have lost the battle against the Wall street and NASDAQ . Or how else we can explain repetition of similar events.

The wages for the modern technology , the patients have to pay a heavy price.

Let us all hope common man with common sense will reign supreme over the sixth sense of the uncommon man . . .

“Ignorance is better than illusion of knowledge”

Dr Venkatesan Sangareddi MD , Assistant Professor of cardiology , Madras medical college Chennai, India

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Anginal pain is a type of visceral pain.It is carried by type  C  unmylinated  nerve fibres.The perception of angina is a complex process.It is a combination of visceral and cutaneous referral pain.

How often is angina silent in diabetes mellitus ?

Presence of  diabetes per se does not make an angina silent. In fact,  if  one takes 100 patients with diabetes  , if angina occur in them , it is more often  , manifest than silent. So , only few of  the  diabetic patients who develop diabetic autonomic neuropathy fail to have angina.The exact incidence is not known.It could be around 20%.

If angina can be silent in diabteics , can they have anginal equivalents ?

This again is not answered in literature. Among the anginal equivalents , the most common is  dyspnea , which  can occur in diabetics.But now , we know dyspnea also needs thoracic nerve signals  from the intercostal muscle spindle and colgi organs.This can also be impaired in diabetics.

Can silent and mainfest episodes occur in a same  patient  ?

Yes.

Once silent does not mean always silent, and similarly once angina is felt it  does not mean he is going to feel the next episode as well !

This  strongly reminds us medical science  is  much a complex  subject and what we know is very little in pain perception.

How is silent ischmia different from silent angina ?

There is considerable  overlap  between  silent ischemia and silent angina

The questions to be answered are 

Which is silent  ?  Is it the angina or is it the ischemia or both ?

Silent ischemia can occur in any individual ,  this is also called as silent CAD . When  ischemia occurs  but  fails  to generate pain it is silent ischemia .Undiagnosed  CAD in asymptomatic individuals is also called silent ischemia or CAD.In this population  Exercise stress testing detects  CAD which was otherwise silent and masked.These patients may develop angina during EST.

During exercise stress testing many times patient has significant ST depression  more than 2mm but still chest pain may not occur.These episodes may either be silent ischemia or  ngina. Many times the EST is terminated before angina is manifest .( Chest pain is the last to occur in the chain of events following ischemia- Concept of ischemic cascade )

What are the other situations where angina can be silent ?

  • Pain perception  and threshold  level is  high ,  so patient indeed has anginal  signals but fails to feel it .
  • Patients on  antianginal medication , fail to feel the angina.
  • Chronic betablocker therapy can exactly mimic  autonomic neuropathy

Is it a blessing for the patient  to have painless episodes of angina ? 

When their  ischemic colleagues , suffer a lot with chest pain it is tempting to think these diabetic patients  are blessed!

Scientifically , this could be true in at least in  some  especially in a patients  who’s coronary anatomy is known  and devoid of any critical proximal lesions. For example a small PDA  lesion can produce  severe angina  , but may be silent  in diabetic and be comfortable .This lesion is  insignificant other wise * !

It should  also be recalled , pain relief has been an important goal for treatment  of CAD .In olden days,  thoracic sympathectomy was done for angina . In fact ,  even in  CABG  , one of the the  mechanisms  for  angina  relief  is attributed  to cardiac denervation.

Caution: Even a small  episode of ischemia can trigger an electrical event .But it is rare.

 How common is silent infarct (STEMI) in diabetic patients ?

In a simple questionnaire we asked the diabetic patients in our CCU how they felt their pain during MI.Most felt it normally as do other non diabetic .  Diabetes  does not make  all anginal episodes  silent. Severe episodes of ischemia may be painful while less severe episodes may be painless. Diabetic autonomic neuropathy  is a  least recognized and  poorly understood complication of diabetes.Diabetes , involves  the vasanervorum of the autonomic nerves.

 The other mechanisms postulated in diabetic neuropathy are

  • Reduction in neurotrophic growth factors.
  • deficiency of essential fatty acids .
  • Reduced endoneurial blood flow and
  • Nerve hypoxia .

Is diabetic autonomic neuropathy treatable ?

Very difficult problem indeed.Controlling diabetes may partially correct  the neural dysfunction.Many add on neuro vitamins and aminoacids are having a good market !

If you successfully treat diabetic autonomic neuropathy will my patient  start feeling the  hitherto silent episodes of angina ?

We don’t know.Logic would answer ” YES”

What is the ultimate effect of cardiac autonomic neuropathy.

Cardiac denervation.  The manifestations  are

  • Tachycardia, exercise intolerance
  • Orthostatic hypotension

 

Silent Myocardial Infarction : A complete list

 

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The irony of medicine is unlimited !  100 years of active clinical  research   failed  to find a specific cure for the rhino virus mediated common cold.In fact  US Govt stopped funding for this .

While ,   complete cure is possible  for many of the cancers, especially hematological ones !

Message 

In medicine there are thousands  of disorder  which have no cure ! 

Cancers ,  constitute  only a  fraction of  them !

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Let us not forget the basics !

  • HT management has been made  easier with the availability of  many  good drugs , at the same time it has become a complex  issue with as many classification and guidelines.
  • The management of HT has evolved over the decades. Now we have realised  HT  is not a simple number game . Reducing the blood pressure to target levels is not  sufficient and is not the primary aim !.
  • In fact we now know controlling the numbers alone is never going to work  , combined risk factor reduction is of paramount importance.
  • HT per se is less lethal but when it combines with hyperlipidemia and diabetes or smoking  it becomes  aggressive.The blood lipids  especially the LDL molecule  enjoy the high pressure environment  ,   penetrate and invade the vascular endothelium.
  • ASCOT  LLA  study has taught us,   for blood pressure reduction to  be effective and reduce CAD  events one has to reduce thier  lipid levels also.So , for every patient with HT there is not only a target BP but also a target LDL level .

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Final message

The tip for better vascular  health is  , all  hypertensive patients should keep their lipids to optimal levels and all hyperlipidemia patients should keep their BP as low as possible .

“Keep your LDL  as low as  your diastolic blood pressure  and  let us  keep it around 70 -80

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                                                 It is now mandatory for all  journals  to declare the  conflict  of interest by the authors  who are involved in medical research .The purpose apparently is to make all transactions or links  between the researchers and their funding agencies transparent .Even major journals  do not go beyond this . Some ensure it , to appear in the first page of  the article.

 What does the the journals tend to  convey to the reader by publishing the conflicts of interest ?

  •  Does it  mean the article in question  may have a bias or indeed have a bias  ?  and readers are warned  hereby !
  •  Do they send across a message  that the  article may not be really a genuine one and the judgement is left to the the consumers of the articles ?

How often a journal article is rejected purely on the basis of  conflicts of interest ?

Most of  journal articles are rejected  for poor methodology, statistical analysis and so forth .We don’t know how often a paper is rejected  due to a conflict issue per se.If this could happen ,bulk  of drug trials would face a torrid time from the editors.

Why , even the leading scientific  journals never indulge in grading the significance of the conflict ?

Here is an example .

accomplish

nejm1

The much hyped drug trial on Hypertension “ACCOMPLISH”  was published in the  world’s most prestigious medical journal recently .It  left  it to the readers to  have their  own assessment  on the conflict issue.

  The consequence of not , grading and investigating  about the conflicts could have  serious  global health  implications both financially and academically .

This study was designed, formulated, completed and published  with a single hidden aim of neutralising the land mark trial  of ALLHAT which recommended diuretics as a first line drug in HT.Apparently diuretics are very  cheap  , effective  generic drugs.

 Is it a scientific rule  that  the  latest evidence  ,  should always prevail over the older evidence ?

No. Science can never have such a rule ! The question is how good and genuine is the evidence.
Just because an evidence is current , it does not  attain a scientific sanctity !

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                                Hypertension is the most common clinical  cardiovascular entity.Left ventricular hypertrophy (LVH) is  an important consequence of  HT.In fact, it is considered as a end organ effect or damage. Others being brain, kidney, and peripheral vascular disease.Knowing about LVH is important because it has been linked to increased cardiovascular events.

lvh-4

                              Though LVH is considered  as a close companion of  HT  it is  surprising  only a minority (15-30%)  show evidence of LVH .Some  experienced clinicians (Level C evidence)  quote even lower < 10 %  .Traditionally LVH was detected by ECG and now it is replaced by echocardiography.

What determines the LVH ?

It will be suprising to note , answer to this question  is  still not  clear .

  • Is it the duration of elevated blood pressure ?
  •  Is it the absolute level of blood pressure ?
  • If so , is it  the systolic BP  , diastolic BP or the mean BP ?
  • Or is it related to the etiology of HT ?
  • There has been no significant correlation between the above parameters

When we don’t know  the answer to a question in medicine , the answer will  generally will be inside the genes !

So in HT also the major determinant of LVH is in the genes that determine the myosin heavy chain  response .

and also ACE gene polymorphism.ACE genes are involved in the expression of growth factors within the myocardium.

An excellent study  on the issue http://www.nature.com/jhh/journal/v17/n3/full/1001523a.html#tbl1

It implicates , gender, age, race etc in the genesis of LVH

Final message

So , the  myocardium does not respond with LVH   in all patients with HT.It happens only in a minority* .Duration of HT can be an important determinant , but  the major factor is  the alteration of genetic switches  within the myocytes How this switches are going to  behave ,  is largely inherited .Regression of LVH is also not uniform again implying lesser role for hemodynamics. (Some studies revealed ACEI have maximum regression  of LVH , later disputed )

*LVH is more consistently seen  in hypertension due to reno vascular  or parenchymal disorders .It is also an observed fact , a  combination of diabetes and HT is more likely to result in  LVH.

The other major issue  that needs explanation in HT/LVH  is   , how much of LVH is due to  myocyte hypertrophy perse  and how much is contributed by interstitial cell hypertrophy(Non myocytic hypertrophy)

This issue will be discussed soon

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                    circulatory                                                                            A normally  functioning  circulatory system is vital for our survival . We have about 6000 ml of  blood, circulating  all over the  body in an  approximate time of 15-20 seconds.The pressure at which this blood moves across the body is called the blood pressure . Hypertension  or simply , high blood pressure is an undesirable  hemodynamic disturbance  in human circulatory system.Systemic hypertension is the most common type of hypertension. The blood pressure is primarily  dependent  on the status of the blood vessel(vascular resistance)  and cardiac contractility. This regulation is under  many neural and hormonal factors.Further  the blood pressure varies depending  upon the blood vessel calibre, and the local milieu.There is a progressive drop in blood pressure from major arteries to the small arteries .The pressure drop is maximum  across the arterioles to reach the venules .The venous circulation has the lowest pressure, it ends up at right atrium with a mean pressure of 0- 5mmhg.

Importance of regional variation of blood pressure.

It should be realised  ,  each organ has it’s own regulated blood pressure.The brain  perfuses by the  intracerebral pressure .The lungs decide how much should be the pulmonary arterial pressure.The kidney not only controls it’s own pressure but also  has a major regulatory role in  systemic pressure by rennin angiotensin system.The examples are numerous, portal system has it’s unique pressure controlling hepatic hemodynamics. The  retinal blood vessels regulate  intra ocular pressure. While the human  circulatory system has a wide variation of blood pressure  across the breadth and length of vascular system,  it is ironical a single snap shot BP with a brachial cuff is used  to define the normality and if it is normal every thing is thought to be  hunky dory !

 

 

It is widely acknowledged now , aging of humanity  is nothing but aging of our vascular system

                                    So we should have new parameters to assess individual organ’s vascular health as well as the currently popular systemic vascular health.The single important factor that determine coronary endothelial damage is the intra coronary pressure.It is never taken into account in any of the cardivascular mortality studies. This is the prime reason for  the widely prevalent conflict in the cardiology literature , namely : Controlling systemic  blood pressure has poor correlation with  cardiovascular outcome. Many of the so called normotensive individuals  have serious hemodynamic injury in their  coronary arteries.This was made apparent in the  ASCOT LLA  study , in which patients with  near normal blood pressure also benefited from statin therapy , implying  endothelial damage could occur at any level of systemic blood pressure.

What is the normal intracoronary pressure  ? When do you diagnose intracoonary hypertension?

The normal intracoronary pressure is around 40mmhg . Intra coronary hypertension as a clinical entity  is yet to be  recognised . There is no defintion available for intracoronary HT  , intracerebral hypertension as well. 

It’s still a  long way to  go , for the cardiology and neurology  community to assess non invasively  intracoronary pressures and  intra cerebral arterial pressure to prevent  coronary events ant strokes.

Final message

Simple risk prediction using brachial cuff blood pressure is a grossly unscientific method (Sorry, i really mean it ) to assess one’s vascular health.There has been  few attempts like vascular endothelial health assessment by fore arm blood  flow , central aortic pressure (Instead of brachial cuff pressure) as an  index for risk predictment and  assessment for hypertension is suggested.

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          During CABG arterial grafts are always preferred over venous grafts , for the simple reason the grafted vessel has to carry arterial blood and not the venous blood. Saphenous veins are tuned to carry venous blood at low pressure.The mean coronary arterial pressure is around 40mmhg and this will damage the saphenous venous endothelium more quickly. The reocculsion rate at 10 years for venous grafts  can reach  60%.


                                                    Left internal mammary artery (LIMA) is the most commonly used arterial graft. This is usually anastamosed with LAD. The lumen of LAD &  LIMA are more or less equal and they match well in character also !

The other advantage  of  LIMA graft  is ,   blood    tends to  flow  both during systole and diastole in a smooth fashion.. Since the venous graft which  hangs from the root of aorta , the  ostium  of venous graft lacks the  hemodynamic benefits of   coronary sinus . (We know the coroanry sinus acts like a  reservoir for  the smooth release of  blood flow into coronary arteries.)

Finally ,  the most important feature of LIMA is

  It is a live graft

LIMA’s proximal origin from subclavian is left intact, so LIMA acts as a live vessel with it’s  vasa vasorum intact ,  which means the endothlium derived relaxing factor (EDRF-Nitric oxide) secretion is not interrupted.This makes the LIMA  an excellent graft , self protected against reocclusion.One may call it a drug eluting graft !

 What is the patency rate for LIMA ?

LIMA patency rates at 10 years is nearly 90 %  .But the graft patency depends on many factors , like diabetes, age, gender, surgical technique ,(Now , beating heart CABG is very popular , where the LIMA patency is said to be slightly lower than conventional CABG) Sequential LIMA grafts, free LIMA graft ( Which  loses the advantage of being  a live graft) have relatively lower patency rates.

What are the other arteries used in CABG ?

Other arteries that could be used are radial artery, right internal mammary artery, and gastro epiploic artery.The patency rates of all these arteries far less than LIMA .

cabg-2

A surgeon testing LIMA flow before Anastomosing it to LAD.

Image courtesy Dr.Mannoj Aggny .You tube

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                                Coronary artery  by pass graft surgery has become the most common cardiac surgery done world over ever since it was first introduced by Favalaro in 1969.The common indications  are, triple vessel disease and left main disease in any of the following situationsE.

Elective CABG(Non emergent)

1.Chronic stable angina

Either emergent or elective

1.Unstable angina

Emergency CABG*

1.Acute myocardial infarction.-Cardiogenic shock

2.Failed thrombolysis

3.Failed primary PCI

4.Complications during routine PCI(Cath lab crashes !  etc)

5.As an associate procedure after a  mechanical complication during MI (Septal rupture, Acute MR etc)

*In emergency situations even a single vessel disease would require a  CABG

Hybrid CABG

Combining CABG and PCI in the same patient is followed in very few centres .(Example LAD graft and RCA angioplasty)This is done in patients who have co morbid conditions who can not tolerate prolonged surgical times.Further there can be situations  one lesion is very ideal for PCI  while for other grafting is the only solution.

Controversial CABG

1.CABG as a primary revascularisation  in STEMI*

(Rarely done now , almost obsolete , primary PCI has almost replaced it  . . . but it is still  useful if performed within 6 hours of MI )

2.Incidentally detected CAD*  following routine coronary angiogram.

( *CABG for incidentally detected asymptomatic CAD is  increasing in many parts of world )

Inappropriate CABG

         If it’s triple vessel disese it must be CABG -CASS study (1980s)

                       Coronary artery surgery study (CASS) still has considerable influence among the  cardiology  community in the decision making process  for CABG , even though it is many decades old .There has been a phenomenal development in both medical as well as interventional techniques since  CASS . (Thrombolysis, Statins, ACEI, PCI  DES to name a few) .

                     When CASS study was done many decades ago,it was believed triple vessel disese constitute a  homogeneous population and  carry  the same clinical significance . For example a 90% proximal LAD , 50% RCA and 50% OM technically qualify for a CABG and unfortunately , some of them are  subjected to it even in  2008 !  Now we clearly know, it is not the number of diseased vessels  that is important, but it’s location, severity , LV function, presence or absence of diabetes . Finally , the presence of revascularisation eligible myocardium must be documented in all post MI patients . (Technically referred to viable & ischemic myocardium ).              

              Currently , with the  PCI  & medical management has grown so much, CABG should be reserved only for, critical triple vessel disese , with at least one proximally located lesion (Mostly  LAD  or Left main ), especially in diabetic individuals.

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