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Archive for the ‘Cardiology -Mechnisms of disease’ Category

Is “Non-flow limiting coronary  lesions  more prone for ACS ?

  • If  your  answer  is “No”, you can skip this article.
  • If your  answer is “Yes” , you need to read this article.

ACS is the commonest cardiac emergency .Thousands of patients are treated every day.Millions of dollars are spent.Bulk of the cardiologist’s life revolves around this entity.

Scattered atherosclerotic plaques in coronary artery lead to ACS either in a random fashion or in a predictable manner .

Still, we are  highly  uncertain about  which lesions are likely to result in ACS ! Some time in the beginning of  21st century, the main stream cardiology media were abuzz with the concept, that non obstructive , non-flow limiting lesions are more prone for ACS rather than more tight  stenosis.

atherosclerosis flow limiting lesion glagov plaque rupture vulnerable erosion fissure vs dissection

I fail to understand how a tight lesion is less  prone for ACS. Tighter lesions are  bigger and must be  prone for more complications . Image courtesy :http://upload.wikimedia.org/wikipedia/commons/9/9a/Endo_dysfunction_Athero.PNG

This reasoning was based on few studies, that lacked  solid scientific proof . In fact the initial  observation was  not made in living coronary arteries rather by autopsy observations .(Later live virtual histological studies came ,  but didn’t confirm this !)

Surprisingly the degree of  anatomical narrowing was conferred  vulnerability  , when we know plaque compositions , morphology and hemo-rheological  factors are many fold important in precipitating ACS . (Lipid content , fibrin cap  thickness, eccentricity , etc)

So where is the truth hidden?

Is it really possible, lesser the stenosis more  is the propensity for rupture ?

 We need to introspect .

“In all probability,  it is a meager statistical illusion”

For every tight lesion there are as many minor lesions scattered around in a given a coronary artery. These can progress into ACS  later.

It is basically wrong to assume non-flow limiting lesions are more prone for ACS than non-flow limiting lesions.To believe so , seriously underestimates  the  culpability of big lesions .It appears a coronary mockery to me  !

At best , we can conclude  non-flow limiting lesions  are not benign and can be an important source of ACS.

An unscientific chain reaction !

If we start believing non flow limiting (say  30%  stenosis ) is more prone for ACS , why we are not stenting all  those lesions ?

If the above concept  is  is applied in cath lab  routinely , the principle of  FFR   which relies solely on hemodynamic impact  will  crash into the dustbin !

Some  more truths

However , It is indeed true  when a plaque is hardened by severe sclerotic process or calcification it is less prone for  rupture and clinical ACS  but can be a source for stable angina.

Is it  justified to assume , larger the plaque the harder  would be it’s content  that  resists ACS ?

Meanwhile , we also know there need not be any lesion at all to cause an ACS.( In a young  smoker ,  100 % thrombotic STEMI  is possible  over an area of coronary erosion caused by endothelial dysfunction ! So , where do we go from here !)

Let us be clear

Are you confused more !   . . . after  reading this article, let us clear it by two-line summary !

As on 2014 ,

  • Symptomatic flow limiting lesion   are tackled by stents.
  • All non-flow limiting lesions  are treated by  high dose Statins  and vigorous medical management.

Final message

Contrary to popular  perception, tight lesions are  more complex, eccentric , soft and are at immediate risk of ACS.

Non flow limiting lesions remain static in most,  regress in many , still  carries  distinct  risk of progression into full blown ACS , at any time if conditions are favorable.

Fixed concepts and ideas in medical science do not help us  taking medicine forward. Especially so, when these are based on assumptions and approximations. If only we redo these studies with the currently available technology (FFR/OCT/NIR the conclusions would be dramatically different. !

Waiting for someone to nullify such false concepts in a more scientific way !

Reference

2.Glagov S, Weisenberg E, Zarins C, Stankunavicius R, Kolletis G. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987; 316: 371–375.

3.Fuster V, Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 1994;90:2126-2146.

4.Ambrose JA, Weinrauch M. Thrombosis in ischemic heart disease. Arch Int Med 1996;156:1382-1394

Postample 
This post was written in 2014. Happy to find a scientific proof to this concept in 2018.
Source :  PROSPECT study

Retrospective angiographic studies and the prospective PROSPECT (Providing Regional Observations to Study  Predictors of Events in the Coronary Tree) study have shown that plaques with severe stenosis carry a higher per-plaque risk for producing clinical events than plaques that cause no or non severe stenosis.

However, such lesions are few, and overall, most ACS are precipitated by plaques  without significant stenosis on an antecedent angiography
weeks or months before. This epidemiology is consistent with the distribution of TCFAs, as shown by a combined angiography and optical coherence tomographic imaging study of nonculprit lesions.

Lesions that caused severe stenosis were twice as likely to be
TCFAs than lesions with only non severe stenosis, but the total number of TCFAs with nonsevere stenosis was three times higher than those with severe stenosis. The mild pre-existent stenosis of most TCFAs and ruptured plaques is explained by expansive remodeling, because such lesions are, on average, large.

The long-held notion that mild to moderate obstructive coronary lesions are responsible for the majority of MIs has been challenged by studies that described significant narrowing in the days preceding MI. However, significant narrowing shortly before MI may be a result of (rather than a precursor) for rupture.

 

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Recently , I came across a   young women  who underwent the following three tests for one episode of syncope after witnessing her pet dog bleeding with  an Injury !

  1. Carotid doppler
  2. Holter monitoring and event monitors
  3. Brain MRI /MR angiogram

This was followed up  by Head up tilt(HUT)  in a premier hospital

After 1 week of investigation ,a diagnosis of  Neurocardiogenic syncope was made and she was reassured and no drugs were prescribed.

(The collective yield of the above three investigation in fixing  a specific diagnosis is  less than 10 % of all known causes of syncope )

Syncope  approach  evaluation

To diagnose  common syncope . . . we need common sense !

Syncope is a dramatic  symptom.It is one of the commonest symptom in ER as well . Life time incidence of syncope is at least one episode in 50% all human life ! The definition  of syncope until recently , was liberal .Any transient loss of consciousness with spontaneous recovery  was termed syncope.

This includes

  1. Hypoglycemia
  2. Anemia
  3. Siezure disorders
  4. Structural  neurogenic (Including ,  brain tumors , Dural hematomas etc )
  5. Panic attacks (psychogenic)

Cardiologists wanted to fix syncope as an exclusive disorder of  circulatory insufficiency.By bringing in a modification in the definition  , ie  syncope is  now defined as a transient loss of consciousness due to   reduction in cerebral perfusion  .

This definition helped cardiologists  to exclude the above entities . Still many would include all in single basket as patient should be seen as a whole and we can’t expect them to  land according to our convenience and classification.

Here is an incomplete* list about causes of  syncope (* 99% complete ?)

Vascular

  • Vaso- vagal syncope in young ( Neuro-cardiogenic , Common , Benign)
  • Autonomic dysfunction of elderly ( Including postural hypotension )

Cardiac

Arrhythmic ( Sinus node dysfunction /CHB/Idiopathic VT/Long QT syndromes)

Structural heart disease

  • Valvular  heart disease  (LVOT/RVOT obstructions)
  • Myocardial disease
  • Rarely ischemic heart disease

Miscellaneous

  • Severe pulmonary hypertension (Including PPH ,  pulmonary Embolism )
  • Paradoxical embolism.
  • Aortic arch disease -Takayasu related arteritis .

Investigation

We have a sophisticated array  of investigation for syncope .It can be a never ending exercise , ranging from  spinal cord evoked potentials to diagnose Shy-drager syndrome ,   . . .  to implanting long-term loop recorders to decode  heart beat behavior.

However , evaluation of syncope is the ultimate wake-up call  to all current generation cardiologists  . . . Why clinical cardiology  should  never  be allowed to die (and  it  will not ! )

Common sense begins with answering  few simple questions . Is it really syncope ?

If  you ask this question three times and with  specific leads to the patient  and the witness ,  truth will come out  . 90% of times it may not be syncope at all (Near syncope, accidental  fall, dizziness ,extreme blurred vision, drowsiness  etc)

If it is syncope , Is there a non cardiac cause ?

It may related to the Hypoglycemia / Anemia /Panic attacks.Get a neurologist opinion , it would be terrible mistake if you miss a space occupying lesion  within the brain. (Missing chronic silent sub dural hematomas is  frequent   in the evaluation of syncope of elderly !)

Ruling out  cardiac syncope is relatively easy

In the remaining  patients  basic investigation like routine blood tests,ECG, ECHO   will help us  rule out most serious cardiac disorders.Similarly  bulk of the electrical cardiac syncope can be diagnosed.(Holter , carotid study in selected few )

Need for neurologist -cardiologist interaction.

Syncope due to VBI,  transient Ischemia attack , Senile vascular dementia  is a grey zone . Many have complex neuronal -vascular mechanisms . What is Consciousness ?  and  What is LOC ?  :Is it the lack of blood or severely depressed nerve signal in the reticular activating system? Lots of interaction between cardiologist and neurologist is required to clear our ignorance.(I  have one such  elderly patient who is intermittently awake ! I call this chronic syncope !)  .

Undiagnosed syncope is not  a crime

Realise the most important lesson in Medicine . If you  have ruled out all serious  causes of syncope you should have the courage to be satisfied with that !

Scientific pursuits has a limit. Searching for the mechanism of a psychogenic  fainting attacks with intra cerebral electrodes is a clear case of  physician acquiring a psychotic  behavior !

Final message

Syncope is not only a dramatic symptom for the patient , it also unfolds a drama of costly  investigations  . .  . many  with  dubious value.

Talk to the patient personally for  10 minutes in a quiet room, try to apply that elusive  clinical sense  . . .   it would rarely let you down !

After thought

What is the true clinical value of * Head up tilt Test (HUT)?

Will be posted soon

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Oral anticoagulant usage has been steadily increasing for variety of  indications.Dengue fever is also  appearing in different avatars with  low platelet counts  and bleeding being a primary risk.

I was recently contacted by a physician , regarding a therapeutic dilemma .A young lady with mitral prosthetic valve and a febrile illness diagnosed as dengue . She has a platelet  count of 100,000 .She is on regular warfarin and aspirin .The physician  wanted to know , should he stop the OAC and aspirin ?

What are the options ?

  • Confirm if it is really dengue.
  • Look for clinical bleeding.INR, platelet function tests are not helpful.
  • Continue OAC.You can do that in most situations.
  • Stop OAC only if there is clinical bleeding  episode.
  • Anti-platelet drug usage  is more tricky .One may stop it if the trend of falling platelet is steep by at least two serial measurement.(or 50% fall from baseline)
  • Fresh blood and platelet infusions should be ready .
  • Finally and most importantly , Inform the patient and family about the difficult decision we are making.

*Is  OAC  safer than aspirin and clopidogrel in dengue ?

It is believed OAC has no major  Impact on platelet function .It may not  pose a threat of excess bleeding in the setting of  falling platelet levels .(*Evidence base -nil )

Another potential situation : DES and dengue

The number of DES in developing countries are increasing  where Dengue is endemic . It is not a surprising  to expect  both to  occur together.

Anti-platelet agents  can be problematic .It is better to withhold it during the active phase of dengue.(If the  stent has recently  been deployed you have no option !)

Final message

1.  Prosthetic valve , Warfarin Dengue .

2. DES, Dual antiplatelet agents ,Dengue.

They  extraordinary events  throw a complex therapeutic task .There are only two options .Continue or discontinue ! Whichever way you do , you explain to your clients (patients!)  the (un)reality games we play.

My personal option would be , with hold all hematological drugs during the active phase of dengue .

It is better to believe in the  natural thrombus fighting force . Leave the job of anti-platelet action  to the dengue virus for a week or two and give oral anticoagulants and dual anti-platelet agents a holiday

It may be foolish to rely on the dengue virus to guard against  prosthetic  valve  and DES thrombus , In reality we have to do that !

Reference

No reference exists.It is a statistical mind game.Individual assessment  should prevail. Either way, if something adverse happens court of law should protect us !

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We know Nitroglycerine(NTG) as a most powerful epicardial coronary dilator  . We use it for instant relief during episodes of coronary arterial spasm in cath lab.

What will happen if we administer NTG over a stented segment ?

Does it dilate it with same vigor ? What will be the consequence  ?

A perfect setting for stent migration isn’t ?

Let us bust the myth around  NTG . NTG  rarely  show  visible coronary dilating effect except in the setting of coronary spasm .

NTG and coronary vasodilatation

Does a LAD with 3 mm diameter become 3.1 or 3.2  and so on with NTG ?

No .It won’t .It is my belief. It is well known , NTG’s action varies significantly in normal and diseased endothelium . Again , there is an irony .It seems , it can act only in normal endothelium , but  we need require it’s therapeutic action only in pathological segments.Further any stented segment would contain   clusters of  both normal and abnormal endothelium .

One more inference is that, stented segment exerts constant pressure on intima making any  pharmacological vasodilatation irrelevant .

Importance of  radial strength of a stent

This issue of vaso-dilator induced  stent migration may not arise in self expanding wall stent with high radial force.But we do not know how long these metals will carry this metallic property .Balloon delivered  stents ( currently used 99% of times ) do not have permanent radial strength .

Final message

I am yet to comprehend what nitrates are expected to do (and what it really does ?)  in a patient post PCI ? (By the way  . . . why we need to prescribe Nitrates it in the first place ? but  In real world most continue to take this for many reasons .)

We need to analyse the micro-vasomotion at the stent -coronary intimal interface.The dynamism in this  narrow space  can be critical  , and may make the difference between life and death !

After thought .

In the hind sight,  this post appears quixotic  for myself . But some one , some where , may generate a great idea  out of it , that will help our patients.

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We know LVH and SHT go together . Mind you , this is not an Intimate relationship.

Widespread utilisation  of echocardiography  has revealed  , definite  LVH occurs only in about 20% (A guess !) of  HT . (Do you know in the Famingham study the incidence of LVH  after 12 year follow up was a paltry 3 % .Will you agree with that ? Mind you , It was in 1969 when Echo was not there )

What determines LVH ?  The clear answer is elusive. It is easy to escape  from the issue by calling it  multi factorial !

Why don’t you try this question .

My guess would be ,  magnitude ( or  even duration of HT !)  is  less important than genetic predisposition  or  associated diabetes ,  renal involvement.Our analysis from  hypertension clinic reveals LVH is many fold common in secondary HT  when compared to primary HT !

I often used to provoke the students by saying if the LVH is gross in HT it can not be primary , 9/10 times  ! Invariably  we find some  other  association or reason for the HT !

Link to related topic in this site

Why-lvh-does-not-occur-in-all-patients-with-systemic-hypertension ?

How-diabetes-modifies-lvh-due-to-hypertension ?

incidence of lV left ventricular hypertrophy framingham study

Next  . . .

How does LVH regress with treatment ?

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Left ventricular  hypertrophy (LVH) is one of the most common  structural heart disease.Systemic hypertension, aortic valve disease are responsible for the bulk of the cases .Some  of the LVH occur due to cardiomyopathy (HCM/Non HCM variants).Athlete’s heart is a physiological response to exercise and  it  is largely a normal entity.

How many patients with SHT develop LVH ?

It is surprising to note , not every patient with SHT develop LVH .In fact estimates suggest only  about 30-40% of chronic  hypertensive individuals develop SHT .

What are the determinants of LVH in SHT ?

  • Magnitude of systolic pressure
  • Magnitude of diastolic pressure
  • Pulse pressure
  • Duration of SHT
  • Age
  • Gender
  • Body  weight/Obesity
  • Effect of treatment

While any of the above factors may operate in determining LVH

none of the above are important than this

“Genetic susceptibility ”

The myosin isoforms are determined by the genes .The re expression of   fetal isoforms in adults is responsible for LVH in many .This is determined by the genetic homogeneity

LVH  in  renal disease

Secondary hypertension due to renal dysfunction is a major determinant of LVH. This is espcially true if the pateints are dialysis dependent.The mechanism are not clear .

Diabetes and SHT :  LVH  friendly forces

When diabetes alone and SHT alone is less likely to result in LVH the combination of these two entities greatly increase the likely hood of LVH.DM induced microangitis amplifies the after load effect of HT and result in early LVH.Further this LVH is different from pure forms of hypertensive LVH  in that the interstitium goes for hypertrophy and in some cases neovascualrisation. In hypertensive LVH it is predominately myocyte hypertrophy  with little interstitial  proliferation. this has important therapeutic implication as any drug which reduce the blood pressure can regress pure myocytic hypertrophy, while in diabetic LVH  regression is difficult to achieve .

Lipid levels inversely related to LVH ?

There is no consistent relation between lipids and LVH .Occasional reports suggest a negative correlation.

Which LVH is associated with diastolic dysfunction ?

It is a well known fact , LVH has major effect on LV diastolic function.But it is also a fact only some forms of LVH develop this. Now it is clear only if the interstitial hypertrophy occur  diastolic dysfunction is manifested.  Even as the as the hypertrophied  myocyte  continue to  relax  the interstitium do not have molecular mechanisms to relax .Hence, as discussed earlier , diabetic hypertensive patient often  develop diastolic dysfunction .

Final message

LVH is not a simple expression of raised after load.It has major  non hemodynamic determinants which if identified , could have important therapeutic implication.

Coming soon . . .

Can  coronary artery  disease induce LVH in the absence of SHT or DM ?

//

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