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Archive for the ‘Thrombolysis’ Category

Cardiologists are grappling with at least  half a dozen time windows  in the management of STEMI. (It can be combinations of any of the following :Symptom – DAPT Loading – Door – Needle /Balloon-Sheath, wire crossing etc ) Time windows are Important in choosing the right (or no)modality of re-perfusion . Though superiority of  primary PCI  is thought to be established in academic community , it  may not be in real world. Published studies that suggest pPCI is superior to lysis at any time window  still lack good evidence.

Why is this long drawn confusion  ? 

One of the important determinant of outcome in STEMI , is the thrombus organisation (hardening )time . Some how we have assumed PCI can tackle hardened thrombus  much better than lysis (In fact the outcome in late PCI is as bad or good as lysis in terms of true myocardial reperfusion in this population.This fact will not be visible in scientific data that’s read superficially .One has  to  mine deep for the truth) (Claeys MJ,. . Arch Intern Med. 2011;171(6):544–549)

Two more virtual pathological Time windows.

While we are preoccupied with certain time windows in STEMI  ,may I suggest  two more  Invisible pathological windows. I don’t know , whether these are presumptive theoretical stuff ,  but understanding these time windows will sharpen our decision-making skills in STEMI.

1.Symptom to  ATO time (Acute total occlusion) 

ery gets occluded(ATO ).This is truly Invisible time window .( Pre-Infarction angina  to Infarct time ) Taking the last episode of most Intense pain need not refer to beginning of ATO / Infarct pain. (ACS being as dynamic process in a 24 hour time span an angina  can even be post Infarct angina!)

2. ATO to thrombus organising (hardening) time

It is obvious time is primary factor that correlates with thrombus organisation. But there is much more to it. It’s not the fibrin organisation alone that makes a thrombus hard. ATO gets reinforced by plaque and tissue material ( like steel rods  inside cement) In other words no one really knows  when does the thrombotic process begin or end  and  hardens thereafter. But we know for certain is  tackling a hard thrombus is difficult for both modalities currently we have lysis and PCI*

.(Almost forgot the third modality,  yes its humble drug heparin(.It can do wonders little slow though , Slowness doesn’t matter beyond 24 hrs is it not ?) Now there can be a role for Warfarin also to get rid of chronic IRA thrombus (Moon JY, N The role of oral anticoagulant therapy in patients with acute coronary syndrome. Ther Adv Hematol. 2017;8(12):353-366.)

There are excellent studies that correlated time window to thrombus hardness.At least in  50%  IRAs with time  window less than 12 hrs have thrombus age more than 24 hours Some of the thrombus material aspirated has been shown to be many days old (Kramer et al PLoS One. 2009;4(6):e5817)

Image source : Miranda C.A. Kramer Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Coronary Death Volume 55, Issue 2, January 2010

How to arrive at the age of the thrombus  ?

It’s a difficult task to guess the age of thrombus with help  symptom onset and ECG .  There  can be 50 %  error as discussed earlier.

Is coronary angiogram helpful ?

There is no good clue to differentiate fresh from old thrombus by just looking at angio shot. Some experts are able do it (Guess it ?)

Poke and feel with guidewire  : This is probably the best way to tell whether thrombus is fresh or old (Still not fool proof ) Most of us do this in STEMI . All is well if guide wire cuts through  smoothly and nice flow is established.(What we call guide wire angioplasty) Procedure is completed with or without a stent ( &residual lesion) .This is the most gratifying and desirable outcome of primary PCI. (Note : Hardness of thrombus can be overcome stiff wires and force.That doesn’t make it a fresh clot ! This is where we may end up with No-reflow)

nrcardio.2016.38-f4

Image courtesy : Karim D. Mahmoud & Felix Zijlstra Nature Reviews Cardiology volume 13, pages 418–428 (2016) Various forms of thrombus aspirated during primary PCI.

When poke test fails  . . . be ready for a long haul or quit

Thrombus is not a single aged mass of blood. It has lawyers of clot with different maturity  ( like shells over earth ).Hence poking has its own side effects too.Some of it can be violent.When  deeper layers of old thrombus is exposed to fresh blood it can create fresh  cycle of clot activation.( Ofcourse we fight it out with DAPT and heparin) Winner of this fight can never be predicted. To conquer the thrombus or quit is directly linked to the cardiologist wisdom.

What about OCT/IVUS ?

They could help us to assess the morphology of thrombus and give  us Indirect clues about the age of thrombus. Some of the experts say they use it efficiently . My opinion is it adds more glamour than true enlightenment .(Mind you , we need to  cross , clear and flush the vessel to complete OCT. The fact that we are able to complete OCT in STEMI settimg would mean  thrombus is  fresh .In that way it may be useful but without a true purpose.)

Thrombus aspirate analysis : Its more scientific way of arriving at the age of thrombus (Any one want to do carbon dating on this ?) , This again lacks practical use as we need to assess  the thrombus age before poking to avoid subsequent complications. It is also not clear whether thrombus in STEMI is more of RBC and fibrin and net platelet content can’t be quantified.This especially true in stuttering ACS where NSTEMI is threatening to become STEMI or vice versa. (Platelets love to hug each other at high shear force , RBCs do the opposite )

Is the Consistency of the thrombus uniform ?

Here comes the importance of the length of the thrombotic segment. It’s estimated the length of the thrombus segment can be anywhere between 1 cm to entire length of the coronary artery distal to the site of occlusion .The initial proximal part may be soft as its directly exposed to DAPT and heparin.The distal thrombus is flushed only with collateral or a trickle of flow from anti-grade .So ,very likely the distal thrombus is harder than proximal.

How does DAPT loading and subsequent heparin interfere with thrombus organisation ?

Loading DAPT has a definite impact and prevents hardening.(But, one issue is it shouldn’t have been happened before administration)

What is the natural history of organised hard thrombus in IRA ?

  • It transforms  into a CTO.(Many of us believe this is dominant theme)
  • Late total recannalisation – 20% by 30 days
  • Partial recannalisation  (More than 20 % ?)
  • Since wide-spread use of predischarge PCI , true natural history is masked.

Final message

Taming STEMI with pPCI  is not always  a time sensitive emergency procedure . It’s important to recall STEMI patients can harbour thrombus with different maturity .We know STEMI can occur even in  patient with chronic thrombotic process also (even a CTO) . This is proven by a simple fact people walk in 3 days after MI casually. Further, during pPCI both early and late arrivals have equal difficulty though they carry different set of problems tackling the IRA.

If we really  believe principles of coronary care is aimed at tackling coronary thrombosis , wisdom  lies in  judicious use of both CCU and Cath lab facilities .Never hesitate to rush back the patient to CCU for a quick lysis (Or Intra coronary) and avoid the potentially prolonged  battle against huge mass of hard thrombus.

Reference 

 

Post-ample : A quote 

Importance of  early arrival of STEMI patient to nearest hospital is huge , not because of the possibility getting an emergent PCI . Rather, it is  due to fact that simply reaching the nearest coronary care center dramatically reduce the mortality.(My guess is , this mortality benefit should be more than Lysis/pPCI put together)

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It was 1912 , Titanic had just sank off the Atlantic . When the world attention was elsewhere , An unassuming young Dr.Herrick J.B silently working in his Michigan lab inquisitively proposed thrombus occluding the coronary artery is the chief culprit in acute myocardial Infarction.It took seven more decades when Davis et all from Glasgow .UK. proved it by doing dramatic angiographic studies soon after STEMI in year 1979.

Now, even after 100 years , we, the confused cardiologists debate endlessly in glamorous global conclaves in exotic locales whether to aspirate these humble looking thrombus, threatening to damage the myocardium with every passing moment !

Why is this controversy ?

My answer

I am failing to understand the concept and the answer is elusive .While every one agrees that thrombus is true culprit, in bulk of the STEMI , still we are not authorised (In an assertive fashion ) either to lyse as first choice or to aspirate as second choice.

It seems vital, thrombus must be tackled vigorously by any means. Drugs,lytics,(Intravenous or Intra-coronary.) by micro and rheolytic catheters .Only documented, flow limiting complex mechanical lesions must be stented. If we are convinced tackling thrombus by mechanical means is problematic (As studies would suggest ) lysis should prevail over aspiration as a routine measure by default isn’t ?

*It’s a been quite a while , the world cardiology community has made it appear thrombolysing a patient who is otherwise eligible for primary PCI ! a “coronary crime*” Ofcourse , I must say , I proudly commit that crime with rewarding results in many MI patients.

*In fact , I would think not promoting or delaying prompt lysis should qualify for the definition.

In the management of STEMI, prehospital lysis followed by a Intensive care in a good coronary care center is best modality.

This doesn’t mean in-hospital lysis is banished. Yes, STEMI is a cardiac emergency , but triaging STEMI patients must be done by scientific means (STEMI risk score) as well with accumulated wisdom .Rush only true emergencies into cath lab. (A best estimate is about 20 % of all STEMI) If we are not able to decide which STEMI will require prompt PCI , it would Imply we need to go back and do once more the basics postings in coronary care of resident days !

An angry counter from a young Interventionist

Only God can tell whether a given patient with STEMI will (or will not) derive maximum benefit from pPCI. We are not yet trained to make that decision by looking at patient and his ECG.So my logic is all STEMIs are equal. I will continue to do emergency angioplasty in all STEMI patients . I expect them blindly to accept all the potential complications arising out of poking the thrombotic milieu in those low risk patients who might have done well with thrombolysis.

Never afraid of challenges. It is like going to war. Casualties are bound to happen.We have enough technology , Imaging , expertise, to tackle all those complex lesions we encounter during primary PCI especially in elderly comorbid patients. We can even do a triple vessel angioplasty , left main etc. Only Yesterday I posted in my nonstop whatsapp group , where I did a dramatic acute angled bifurcation angioplasty for a stable STEMI patient that required a iFR guided jailed side branch assessment and 3d OCT transmitting stunning snaps of fresh thrombus, ending with a semi culotte procedure.The patient is doing well with a Impella 2.5 device and a high frequency ventilator support and my anesthetist has promised me to wean him soon ! I must actually thank his Glo-Health plus Insurance company for clearing the procedure.

An Important tip for complex lesions during STEMI

We need to know there is always a saving grace , if for some reason we couldn’t accomplish PCI due to complexities of the lesion with multiple IRA mimickers. We can always sheepishly thrombolyse these patients inside cath lab . . . a modality just few minutes ago would have been ridiculed with all our vigor to convince the anxious family for a costly Invasive procedure !

Reference

3. Herrick Original paper . https://jamanetwork.com/

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Many  readers  of this site might have wondered  , about a  series of biased articles  pulling down the  superiority of pPCI in STEMI.

This  French  study (FAST-MI) throws stunning data  from the real world. Initial Fibrinolysis* defeated pPCI in all aspects of coronary reperfusion !

FAST MI primary PCI  trialFAST MI primary PCI  trial 2

*When we say fibrinolysis arm it means Pharmaco -Invasive approach .Today our  brain  is irreversibly conditioned to believe standalone fibrinolysis is  forbidden in STEMI . (Which I strongly disagree!) I am sure, very soon another stunning study will unmask the truth about standalone fibrinolysis  as well !

Final message

  • The truth  is ,  pPCI is really a superior  modality in some of the complicated  subsets of STEMI that too if performed fast.
  • In all other situations Initial fibrinolysis will rule supreme !
  • pPCI is not an Innovation for mass consumption!
  • Hence, “the roof top call” for  pPCI for every STEMI is nether desirable nor feasible.

Now, we have this evidence from France (Which was well known to us a decade ago) As always , truth takes time to arrive , while falsehood can come instantly !

 

In 2014 , after two decades of celebration of pPCI  the flagship Circulation journal  throws this Editorial !

primary pci vs thromolysis debate fast study

 

 

 

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We know  streptokinase  is a non fibrin specific   agent that   results in systemic lytic state and hence more chance of bleeding.

TPA is fibrin specific  and it  will act only on fibrin  bound to clot , hence systemic bleeding risk should be less.

However , in real world , it is well  documented  stroke risk with TPA is consistently more than streptokinase .(It varies between .0.3-.5% with streptokinase , 0.7-to 1%  with TPA)

How do you explain this apparent  paradox ?

Possible explanations.

  1. The fibrin selectivity pf TPA is not absolute* .
  2. The lytic power of  TPA is more hence stroke is more likely.
  3. The FDP* released by TPA can trigger a systemic lytic state
  4. In the  post TPA protocol   heparin  is  mandatory and  this  contribute to stroke risk.

*What happens o fibrin degradation products (FDP) levels after TPA ?

FDP levels do increase after TPA  .This peaks at 1 hour after lysis.it Correlates well with risk of stroke.(Ho CH, Wang infarction.Thrombosis Research ).

Reference

This is an excellent review with analysis from 14 studies with total of 142 907 patients with thrombolysis

A meta  analysis of thrombolytic agents streptokinase vs tpa tnktpa  stroke risk fibrin slectivity

Ho CH, Wang SP Serial thrombolysis-related changes after thrombolytic therapy with TPA in patients with acute myocardial infarction.Thrombosis Research

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Pharmaco Invasive approach (PIA)  is the new mantra in the management of ACS.It simply means the intention to do PCI   should always  be the  driving force in every STEMI patient , whether the Initial lysis is successful or failed .

This concept is exclusively created  for centers where there is no cath lab (This would include  hospitals  with  inactive labs ,  cardiologist  team  who lack required expertise !)

What to do after lysis ?

  • If  the initial lysis has failed  “Rush” them  for an emergency  PCI.
  • If  Initial lysis is successful  “Send”  them for PCI in a  less emergent manner.

Generally the  time window for PIA is 3-24 hours.  In failed lysis  technically it could be as early as 1 hour as that is the time to assess the efficacy of initial lysis. (Of-course the theoretical transfer  time to be added )

Why the 3 hour period for PIA ?

We know routine   facilitated-PCI(f-PCI)  with various combinations of  fibrinolytics  and 2b -3a antagonists is a failed concept. (FINNESS )

One of  the primary reason for f-PCI to fail is , the  very narrow time window  between drug and balloon which somehow  end up in more hazard  (Needle -Balloon window)  .

If they are very close the harm is likely to be more ,still they have to be closer if lysis has failed .(This is the reason many old studies had depressing results with even with the  concept  of rescue PCI !)

Lytic agents and PCI  even though we assume to compliment each other real world evidence indicate they share a love hate relationship .

 

Beware, PIA is one form of facilitated  PCI.

If we agree routine  f-PCI is a failed concept we are in for real trouble. PIA indeed may  masquerade as f-PCI  if  you combine lytic and PCI in sequential fashion in a hurry !

My point of view is is a  successfully lysed STEMI should not be rushed to cath lab .If  he  some how reach the  cath lab ultra fast manner , it behaves like a  f-PCI and he is going  to harmed more !  by the current evidence base  isn’t ?

If the  inital lysis was successful , with a  less complex anatomy, it is  possible your PCI  that is going make the lesion more vulnerable.

(The other  issue is tied with flawed human instinct. One can’t stop with CAG in a PIA* .Interventional  cardiologists rarely have the courage to leave a well recannalised IRA  without PCI.)

**Still , you need to facilitate the PCI in complex intervention in  true rescue situation.That’s were we require the collective wisdom.

Assumptions galore in ACS

We have difficulty in  identifying true success and failure of lysis .Vagueness with which we make decisions  in CCUs and cath labs  , is exemplified by the following facts. Post thrombolysis , 40%  patients with persistent ST elevation are asymptomatic and 30 % of all those with complete  ST regression , still have occluded IRA.

We are also uncertain when do  the muscle  truly  die after a STEMI ! It is 6 hours in some, 12 in many, 24h  in few , 36 h in a lucky ones .The role  of collaterals, intermittent patency , individual variation  resistance to myocardial hypoxia injury cannot be  be quantified .

Final message

  • The importance of Needle to Balloon  time (NBT) time in PIA  is to be strongly emphasized.
  • This time can vary between 1-24 hours .But practically it will start from 3 hours .
  • The irony is , we have conflicting  engagement with time in PIA. We have to  strive for both narrowing as well as intentionally  prolonging this time window .
  • It has to be narrowed in true rescue situations and   optimally prolonged (Or is it indefinitely ! ) in non rescue situations !

After thought

Can we do pharmaco-Invasive approach(PIA)  in PCI capable center ?

  • Even in PCI capable centre one may get struck in proceeding with anticipated primary PCI for various reasons . If delay is anticipated we  have to fall back on thrombolysis .This we call as  unscheduled  or bail out  phamaco Invasive strategy .
  • Intentional PIA   in a PCI capable hospital for all low risk MI is also a viable and option .Never think  primary lysis   for STEMI  even if we  have lab ready is serious medial crime . After all , pPCI has a very  marginal benefits in if any in all low risk STEMI!

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